Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

Understanding Shwachman-Diamond Syndrome Through Zebrafish Research

Shwachman-Diamond syndrome (SDS) is usually caused by mutations in the SBDS gene, but some patients have mutations in another gene called DNAJC21. Because SDS is so rare, and mutations in DNAJC21 are even more rare, researchers often use animals, known as model organisms, like fish, mice, fruit flies, or other animals to study it. Using model organisms to study SDS and other rare diseases helps scientists better understand the disease and develop potential treatments. This is why SDS Alliance, in collaboration with the Jackson Laboratory, is committed to generating a mouse model with mutations in the SBDS gene that scientists can use to understand SDS and ask important questions that will advance treatment development for SDS.

In the SDS & Science Snapshot this week, we are highlighting a new study published by scientists at the CHEO Research Institute (Ottowa, Canada) and colleagues which used zebrafish, a different model organism than mice, to investigate the impact of germline mutations in DNAJC21 on the development of SDS-related symptoms and identify potential treatment opportunities.

Why Zebrafish Are Important for SDS Research

Zebrafish are tiny fish that are often used in research because they share many genetic similarities with humans. Their fast growth and transparent embryos make them ideal for studying how genes work, particularly in conditions which affect the blood and bone marrow (like SDS). The use of zebrafish as a model organism for SDS and SDS-associated conditions is not new – zebrafish have been used as a model organism for SDS in previous research studies as well (here is a link to one example).

In this study, scientists used zebrafish to model SDS caused by mutations in the DNAJC21 gene. By creating zebrafish with similar mutations, researchers can observe the effects of these mutations in a living organism, which provides valuable insights into how the disease affects humans. For more information about the importance of zebrafish and other model organisms in research, you can watch the video below.

Key Findings and Potential New Treatment Opportunities

The researchers found that zebrafish with mutations in the dnajc21 gene (the zebrafish equivalent of DNAJC21) showed symptoms similar to those seen in SDS patients. These fish had lower numbers of certain types of blood cells, grew more slowly, and had other health problems. This shows that the dnajc21 gene in zebrafish is important for normal blood cell production and overall growth, just like the DNAJC21 gene in humans.

One of the exciting findings from this study is that the researchers identified a new role for the zebrafish dnajc21 gene in controlling the production of nucleotides, which are the building blocks of DNA and RNA. When nucleotide levels were low (as a result of mutations in the dnajc21 zebrafish gene), the zebrafish developed problems with blood cell production. However, when the researchers gave the fish extra nucleotides, their blood cell counts improved. This suggests that treatments aimed at increasing nucleotide levels might help manage SDS symptoms in humans.

The Role of p53 and its Impact on SDS

The study also explored the role of another gene shared between zebrafish and humans, TP53, which is known to be involved in cancer and cell death. When the researchers introduced a somatic tp53 mutation into the dnajc21-mutant zebrafish, they observed some improvement in blood cell counts. However, this also led to other problems, like the development of myelodysplastic syndrome (MDS), a condition where blood cells don’t mature properly and can lead to leukemia. This finding highlights the complex relationship between different genes in SDS and how they can influence the disease’s progression. For more information, you can review this previous SDS & Science Snapshot which discusses another study investigating the role of acquired (or somatic) TP53 mutations in individuals with SDS.

What This Research Means for SDS Patients and Families

Although this research is still in the early stages, it provides a valuable foundation for future research studies and potential new treatments development. Research using zebrafish and other model organisms help scientists understand SDS better and offers hope for new treatments. By uncovering how different genes contribute to SDS and SDS-associated conditions, researchers can develop more targeted therapies. For patients and families living with SDS, these findings are a step forward in finding ways to navigate life with SDS and improve treatments.

Ketharnathan S, Pokharel S, Prykhozhij SV, Cordeiro-Santanach A, Ban K, Dogan S, Hoang HD, Liebman MF, Leung E, Alain T, Alecu I, Bennett SAL, Čuperlović-Culf M, Dror Y, Berman JN. Loss of Dnajc21 leads to cytopenia and altered nucleotide metabolism in zebrafish. Leukemia. 2024 Aug 13. Epub ahead of print. PMID: 39138265.

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Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

New Publication by the SDS Alliance: From Challenge to Opportunity: How Shwachman-Diamond Syndrome Became a Promising Target for Therapy Development

The efforts of the SDS Alliance are bringing new hope to the SDS community. SDS Alliance’s very own President and CEO, Eszter Hars, Ph.D. and Dr. Lisa McReynolds, Assistant Clinical Investigator at the National Cancer Institute and member of the SDS Alliance Medical and Scientific Advisory Board published an article in the peer-reviewed Journal of Clinical Pharmacology and Therapeutics. In this article, they described how the efforts of SDS Alliance and other investigators in the SDS community have positioned SDS as a promising target for new therapies.

This figure from the article summarizes why SDS is a model rare disease and ready for therapy development. De-risking means removing barriers in research, in order to give therapy developers confidence that their investment is worth while and that therapy development will be financially viable for SDS.

Below, we’ll explore how publishing these perspectives and advancements in a peer-reviewed journal pave the way for more research, better care, and the potential for life-changing treatments for the SDS community.

The Importance of Publishing in a Scientific Peer-Reviewed Journal

Publishing in these high quality journals allows high quality work to reach doctors and researchers who can use this information to further advance research. Researchers of a wide range of life-science disciplines rely on special search engines to keep up to date on the latest research and scientific insights. Instead of Google, they use PubMed, which is focused on scientific journals and other publications and organizes the basic information about the articles in a way that allows users to find relevant articles quickly, easily, reliably, and FREE. Learn more about PubMed below, and explore additional videos to dive deeper. Or just try it yourself!

By publishing this article in a high-quality scientific journal - indexed by PubMed - the SDS Alliance is now able to reach doctors and researchers who are not yet engaged in the SDS community, in addition to existing experts. Here is the link to our article on PubMed. PubMed users can set up alerts based on their research interest and keywords, to receive emails if a new article is published that match those search criteria. For example, Shwachman-Diamond Syndrome, or inherited bone marrow failure, or congenital neutropenia. Now all doctors/researchers who use alerts or who search PubMed regularly will have received an alert about our publication, and have the opportunity to learn about a new angle to see the SDS patient community and our work.

Below, you can see how our article appears on PubMed. We circled the button that leads to the full text of our article on the journal publisher's website (Wiley). There, you can read the full article - both the web version (easier to read on a screen) and a PDF version that looks like the printed version that will be distributed to libraries and subscribers later this year.

When research is published in a peer-reviewed journal, it means that other experts in the field have reviewed and validated the work. This process ensures that the information is accurate, reliable, and valuable to the scientific community. For the SDS community (and many other rare disease communities), being published in such journals is important because it increases credibility and visibility. It helps attract attention from researchers, companies, and healthcare providers who might not be aware of SDS. This recognition can lead to more research, funding, and eventually, new treatments that could make a big difference in the lives of SDS patients and their families.

Understanding ICD-10 Codes and Their Importance in Rare Disease

ICD-10 codes are special codes used by doctors and hospitals to identify and track diseases. For rare diseases like Shwachman–Diamond Syndrome (SDS), having a unique ICD-10 code is a big deal. It helps doctors and researchers track the condition and learn more about how it affects the SDS patient community over time, what treatments work better than others, what complications to watch for, and other invaluable data. This data can be used to understand the disease better and to develop new treatments. In 2023, SDS received its own ICD-10 code, D61.02, which marks a significant step forward for the SDS community. This new code makes SDS more visible in the medical world, leading to better care for patients and more research opportunities. If you haven’t already, we encourage you to share the ICD-10 code for SDS, D61.02, with your care team! 

Why The Work of SDS Alliance Matters for Developing New Treatments

This article highlights why it's crucial to bring SDS to the attention of biopharmaceutical companies—those who develop new medicines. SDS is an exceptionally good candidate for therapy development because its genetic causes are well understood, and there is strong support from the patient community and researchers. At SDS Alliance, we are dedicated to supporting SDS research and patients, and continue to work hard to establish and foster relationships with companies who support the goals and mission of SDS Alliance, including therapy development.

With the new ICD-10 code, there’s now a new path for gathering data and understanding the disease better, which can aid in the development of effective treatments. This makes it more likely that companies will see the potential in developing therapies for SDS, which could change the lives of those affected by this rare condition.

The Promise of SDS Alliance to Support the SDS Community

With this publication, SDS Alliance highlights and summarizes our work dedicated to the SDS community to improve the lives of those with SDS and to positively contribute to the development of new therapies. Securing the ICD-10 code for SDS is one of the impactful contributions toward making SDS visible and accessing relevant data for therapy development strategies.

By supporting research, providing important tools and data, and fostering a strong patient community, SDS Alliance is not only helping to bring attention to SDS but also paving the way for new and better therapies. Together, our work ensures that SDS patients are heard and that our needs are at the center of therapy development in the future.

Hars ES, McReynolds LJ. From Challenge to Opportunity: How Shwachman-Diamond Syndrome Became a Promising Target for Therapy Development. Clin Pharmacol Ther. 2024 Jul 22. Epub ahead of print. PMID: 39039619.

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Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

Understanding the Role of Blood and Bone Marrow Stem Cell Mutations and Their Impact on SDS Progression and Treatment

Shwachman-Diamond Syndrome (SDS) is a rare genetic disorder that affects the bone marrow, pancreas, and skeletal system. Recently, researchers have made significant strides in understanding how somatic (or acquired) genetic mutations play a role in the bone marrow failure of patients with SDS. Dr. Alan Warren and his team recently published a review of these advancements in Blood, the official journal of the American Society of Hematology. 

One study highlighted in this review used advanced techniques to map relationships between the blood and bone marrow stem cells in patients with SDS, shedding light on the mutations that may influence the development and progression of MDS and AML. This was done by analyzing individual stem cells from the blood and bone marrow of ten SDS patients aged 4 to 33 years. Researchers discovered that most of these patients had large groups of bone marrow stem cells with a lot of somatic (or acquired) genetic mutations, such as mutations in the TP53 gene, a pattern usually seen in much older individuals. This suggests that blood and bone marrow stem cells in SDS patients are affected early in life, contributing to the development of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) at younger ages. 

Another recent finding highlighted by this review, was the role of acquired (somatic) mutations and how the different somatic mutations interact. While acquired (somatic) mutations were common in the blood and bone marrow stem cells of patients with SDS, not all somatic mutations led to severe consequences. Interestingly, some somatic mutations seemed to help cells survive better despite the SDS-related defects. These "rescue" mutations potentially lower the risk of disease progression to MDS or AML. However, when acquired TP53 mutations occur in both copies of the gene, it can lead to severe conditions like MDS or AML. For more information regarding the development of clones and the difference between somatic and germline variants, watch the video below or review these previously published SDS & Science Snapshots (Somatic and Germline Variants or The Difference between Germline and Somatic Genetic Testing).

The review published by Dr. Warren and his team shared that multiple recent studies have had similar findings, reporting that up to 72% of SDS patients often develop clonal hematopoiesis (CH). CH happens when some blood and bone marrow stem cells with specific “signatures” of acquired (or somatic) mutations start to dominate, but other features of MDS and AML are not present in the bone marrow. The acquired CH mutations observed in SDS patients were usually different from those seen in older adults without SDS. By tracking these mutations over time, researchers hope to better understand how they affect disease progression from CH to MDS and AML. For more information about clones, how they develop, and how to monitor the development of them, watch the video below.

Dr. Warren and his team emphasized the timing of when these somatic mutations occur is also crucial. By building a "family tree" of stem cell mutations, researchers can estimate when specific mutations happened. Some mutations in SDS patients can occur very early, even before birth. Following the “family tree” of somatic mutations and how they relate to early somatic mutations highlights the importance of monitoring SDS patients from a young age.

Dr. Warren presented part of this work and background virtually as part of the 2024 Expert Webinar Series, hosted by our Australian partner organization, Maddie Riewoldt's Vision, focused on funding research to discover cures for Bone Marrow Failure Syndromes.

For families and patients with SDS, these findings emphasize the importance of regular bone marrow biopsies and somatic genomic testing (also known as NGS) on these bone marrow biopsy samples and/or on peripheral blood samples. Understanding which somatic mutations are present in the blood and bone marrow of SDS patients can help doctors predict the risk of disease progression and make informed decisions about treatments, including the potential of bone marrow transplant. As research advances, it may also lead to new therapies that target specific somatic mutations or pathways, offering hope for better outcomes in the future.

Cull AH, Kent DG, Warren AJ. Emerging genetic technologies informing personalized medicine in SDS and other inherited bone marrow failure disorders. Blood. 2024 Jun 21:blood.2023019986. Epub ahead of print. PMID: 38905596.

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Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

Unlocking the Secrets of Early Development in SDS with Induced Pluripotent Stem Cells

Shwachman-Diamond syndrome (SDS) is a rare genetic disorder that affects the bone marrow, leading to a shortage of blood cells. It can also cause other problems in the body and increase the risk of leukemia, a type of cancer. The disorder is mainly caused by mutations in the SBDS gene, which is important for making ribosomes, the cell’s protein factories. Without proper SBDS function, not enough ribosomes can form, leading to many of the issues seen in SDS.

In the SDS & Science Snapshot this week, we are highlighting a recent study led and published by Dr. Yigal Dror, a leading physician-researcher on inherited bone marrow failure syndromes from The Hospital for Sick Children (SickKids in Toronto). In this study, Dr. Dror and his research team wanted to find out exactly when the blood cell problems of individuals with SDS begin during development with the hopes of guiding future research in therapy development.

To do this, Dr. Dror and his research team created a special type of cell called induced pluripotent stem cells (iPSCs) using cells from bone marrow samples from SDS patients and healthy controls, which can turn into any cell type in the body. This ability to “shape shift” makes iPSCs a powerful tool for studying early embryonic development, as they can be used to observe how diseases or genetic conditions affect the formation of different cell types from the very beginning. Additionally, iPSCs can be used to model diseases in the lab, allowing scientists to explore new treatments and understand the underlying mechanisms of various disorders without the need for embryonic stem cells. For more information about the important use of iPSCs in research, you can watch the video below.

Key Findings from this Study:

1. Lower Efficiency in Cell Reprogramming: The researchers found that it was much harder to create iPSCs from SDS patients compared to heathy donors, suggesting that cells from SDS patients are either less fit or have a reduced ability to be reprogrammed into stem cells.

2. Defects in Blood Cell Formation: When the iPSCs from SDS patients were encouraged to become blood cells, they formed far fewer blood cells than the healthy iPSCs. This means that the blood cells in SDS patients have trouble developing properly, which can explain the issues with healthy blood cell development (like neutropenia) seen in SDS patients.

3. Early Developmental Issues: The study also showed that the problems start at a specific stage of blood cell development, known as the early emerging hematopoietic progenitors (EHPs) stage. This is an early step in the process where stem cells start to become specialized blood cells. SDS cells had fewer EHPs, and these cells were less able to grow and multiply.

4. Potential for New Treatments: One exciting aspect of this study is that the researchers found that adding back the SBDS gene to the SDS iPSCs improved their ability to form blood cells. This suggests that gene therapy, which aims to correct the defective gene, might be a promising treatment for SDS. Additionally, understanding the specific stages and processes affected by SDS helps in designing drugs that can target these problems more precisely, and provides a rationale to apply treatments as early in life as possible.

5. Mapping Gene Pathways in SDS: Lastly, the researchers in this study investigated the gene expression during early development of these iPSCs from SDS patients. By analyzing these iPSCs, they identified important genes and cellular pathways that are activated or repressed at various stages of cell development. This detailed mapping of gene activity may help in understanding the differences between healthy and SDS iPSCs, providing valuable information for developing targeted therapies for SDS.

Understanding exactly when and how blood cell problems start in those with SDS can help scientists develop better, more effective treatments. By knowing that the defect begins at the EHP stage, researchers can target this stage to find ways to prevent or correct these defects. These findings could help lay the groundwork for new therapies that can improve blood cell production in SDS patients, reducing the need for frequent treatments and improving quality of life. This also underscores the critical importance of early and accurate diagnosis of SDS, so that any treatment can be started as early in life as possible, when the benefits may be the biggest. With continued research, there is potential for significant improvements in managing and treating SDS!

Lagos-Monzon A, Ng S, Luca AM, Li H, Sabanayagam M, Benicio M, Moshiri H, Armstrong R, Tailor C, Kennedy M, Grunebaum E, Keller G, Dror Y.

Aberrant early hematopoietic progenitor formation marks the onset of hematopoietic defects in Shwachman-Diamond syndrome. Eur J Haematol. 2024 Jul 5. PMID: 38967591.

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Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

SDS Alliance Announces Collaboration with Rare Genomes Project

Timely and accurate diagnosis of Shwachman-Diamond Syndrome (SDS) is critical for patients to access optimal care, education, and community support. We are excited to announce our new collaboration with the Rare Genomes Project (RGP) at the Broad Institute of MIT and Harvard. The RGP is a free and remote research program using genomic sequencing to look for the genetic cause of rare diseases, such as SDS. Eligible families will be asked to provide a blood sample and medical information. If a result is found, the RGP team will work with your doctor to confirm the result.

What is the purpose of this study?

The Rare Genomes Project is a research study focused on patients and families with rare and genetically undiagnosed conditions, now including those suspected to have SDS. The RGP uses genomic sequencing to search for the cause of rare disease in these families and hopes to accelerate the rate of rare disease diagnosis in the process. 

How is the genetic sequencing done?

What is particularly exciting about this project is that it uses Whole Genome Sequencing (WGS), sequencing the entire genome, not "just" the coding sequences called as genes (as in Whole Exome Sequencing (WES)) but also everything in between. Are you curious how WGS is done? Check out this short video overview, below. For more details about the difference between WGS and WES, check out this video.

Who is eligible to participate in our new collaboration?

• Those who have a clinical suspicion for SDS, including a history of two or more of the symptoms listed below. (“A history of'' means that these symptoms may have happened in the past and resolved by the time participation in the RGP is considered.)

Exocrine pancreatic insufficiency (EPI): Decreased pancreatic enzymes (serum trypsinogen or pancreatic isoamylase), decreased fecal elastase, malabsorption, or steatorrhea

Hematologic abnormalities: Cytopenias including neutropenia, hypocellular bone marrow, bone marrow failure, or MDS/AML

Skeletal dysplasia: Rib cage/thoracic abnormality, metaphyseal dysostosis, extremity abnormalities, scoliosis, or abnormal bone density

• Individuals with a suspected genetic cause that has not been identified due to prior testing being negative or inconclusive OR a lack of access to genetic testing. (This means that patients who have received genetic testing previously ARE eligible to participate, as long as prior testing has not yielded a diagnosis.)

• Applicants for the RGP must live in the United States.

How do I get involved?

Participation is initiated by eligible patients and families by completing an online application which asks questions about personal and family medical history. The RGP research team will review your application to determine eligibility - this application review process may include a request for additional medical records. Eligible families will also be invited to participate in a virtual introductory meeting to meet the RGP team and discuss participation details such as submitting a blood sample. For more information, you can watch the video below or visit this webpage on the RGP website.

Will I receive genetic testing results?

The goal of the RGP-SDSA collaboration is to find the genetic explanation for SDS in each family who enrolls, but the RGP cannot guarantee that they will have a result for each family. Because this is research-based genetic testing, the process is expected to take longer than routine genetic testing. If the RGP finds a genetic variant(s) that may explain SDS in the family member with the condition, the RGP team will work with affected individuals to clinically confirm and return the results. The RGP does not return results to unaffected family members.

How will I receive genetic testing results?

If the RGP finds results that they believe explains the underlying cause of SDS present in your family, they will contact you and ask if you would like to have the findings clinically confirmed in a CLIA-certified laboratory. A genetic counselor on the RGP staff will work with a doctor of your choice to order testing through the CLIA-certified lab. The doctor who orders the clinical test will be the one who shares the results with you.

If this project sounds like it could benefit you or a loved one, we encourage you to fill out an application on the RGP website.

More resources

• The SDS Alliance team is available for guidance at connect@SDSAlliance.org. 

• At SDS Alliance, we have assembled resources for possible patients and their healthcare providers to access no-cost testing options, wherever you are.

• This page is dedicated to the SDSA partnership with the Rare Genomes Project to provide access to whole-genome sequencing on a research basis to US residents.

• If this program doesn't work for you, please check out our other resources or email us at connect@SDSAlliance.org. 

• Download a printable flyer here, available in English and Spanish:

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At the beginning of 2023 we found out with great joy that we will be expecting our second child and we could not be happier knowing that our family will grow.

The pregnancy was monitored carefully each trimester and for the first two, it seemed to be all ok, the baby was growing as expected, everything was within normal parameters. That was until one of our check-ups during the 3rd trimester, where after an ultrasound examination, the doctors informed us that it seems that the baby's limbs are not growing in accordance with his gestational age and the doctors were starting to suspect a possible genetic condition (achondroplasia).

Of course, we were devastated to even consider that our yet unborn baby boy could be in any way sick, and went through all the possible stages - crying, denial, anger, - you name it... Regardless, there was nothing we could do but wait and see...

Finally, October arrived and Octavian was born at the maternity hospital in our city in Romania. His APGAR score was 9, as for the first hours outside the womb, he had some breathing related issues, but thank God, afterwards his breathing got better and did not need to undergo any more oxygen therapy. He was quite small, 46 cm and 2.6 kg but was from the start, very very beautiful.

The genetics department from the maternity hospital suggested we should test him for achondroplasia, but as my parents are pediatricians, they both suggested that it makes no sense, because from their experience it was clearly not the case of achondroplasia. They were the ones that encouraged us to go for the Whole Exome Testing and did so in November.

For the first 3 months, Octavian was doing quite well, he was eating well (breastfed + extra formula) and was gaining steadily weight at a normal rate. We were very proud of our little man because even when he had the misfortune of contracting pneumonia from his older brother, he still did not lose weight, and was still eating with pleasure.

Close to Christmas time, he started eating smaller and smaller portions, and showing signs of abdominal distress, so we tried to switch to any possible formula for the coming period and giving him any possible supplements to help with digestion. Now we entered the stage where he simply stopped gaining weight and was somehow blocked at 3.9 kg for almost 2 months...

In the meantime, we got the results back from the Whole Exome Genetic Testing and we celebrated because it clearly stated he has NO achondroplasia. For about 2-3 days we just couldn’t realize that there was something else highlighted in the results:

• The patient is heterozygous for EFL1 [...], which is a variant of uncertain significance (VUS).

• The patient is heterozygous for EFL1 [...], which is a variant of uncertain significance (VUS).

Biallelic pathogenic variants in EFL1 have been associated with Shwachman-Diamond syndrome 2 (SDS; MIM #617941; GeneReviews NBK1756), an autosomal recessive disorder characterized by exocrine pancreatic insufficiency, bone marrow dysfunction, skeletal abnormalities, and short stature.

At some point, again my parents suggested to test his elastase levels from his stool and we got back two consecutive results for exocrine pancreatic insufficiency….Now it started to become clear to us that it could be the case that our son has SDS….It came as a shock to us to find out that at our centers for Cystic Fibrosis, the doctors have never seen SDS…We felt pretty much on our own, until one day we went online and found the SDS support group and got in touch with multiple people and patients and were all of the sudden surrounded by information and encouragement from the group.

Eszter Hars of the SDS Alliance was one of the people that helped us the most from the community, she helped us get in contact with specialist in Europe that have experience with SDS and in April we were lucky to be accepted for a visit at Dr. Cipolli Marco in Verona Italy. We were happy to be in the hands of specialists that know how to handle Octavian’s condition.

[Editorial comment: due to the mutations being classified as VUS, the patient received his diagnosis by an SDS expert based on clinical (symptom) findings, which is known as a clinical diagnosis as opposed to genetic confirmation. About 10% of SDS patients are diagnosed clinically].

This condition was classified as being mild, showing skeletal abnormalities in the form of a narrow chest and pancreatic insufficiency. His bloodwork is ok, showing no signs of neutropenia or anemia.

Octavian is now 8 months old. He is still small for his age and is still struggling to reach the milestones that most kids reach by the age of 8 months because of his hypotonia. He is now 60cm tall and weighing 4.6 kg.

We have come a long way in just 8 months, 8 months ago we never heard of SDS and never even considered the chance of our child to suffer from a rare disease… We learned in this short period that we are strong together, and that there is a community that we can rely on when in need.

[Written and submitted from Octavian's dad, Raul]

Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

New Insights into Lung Microbiomes and Bone Marrow Transplant Outcomes

When children undergo bone marrow transplant (BMT), such as those with Shwachman-Diamond Syndrome (SDS), even small infections, such as respiratory infections, can become very dangerous. A team of scientists around the world recently published a new method to quickly identify all the microscopic organisms in the lungs of these children after BMT with the hopes of improving transplant outcomes. 

This collection of microscopic organisms, referred to as the microbiome, includes bacteria, viruses, fungi, and other microbes, that live all over our bodies, including inside the lungs. Just like the gut microbiome, the lung microbiome plays a crucial role in maintaining health and protecting against infections. A balanced lung microbiome helps the immune system function properly, whereas an imbalance can make individuals more susceptible to diseases and infections. The researchers of this study discovered that certain groups of microbes in the lungs can predict which patients after BMT are at higher risk of dying from lung infections.

The video below explores the origin, purpose, and importance of the human microbiome.

Researchers in this new study used a technique called metagenomic next-generation sequencing (mNGS) to examine the microbiome of lung fluid from many pediatric patients after BMT. This method allowed the researchers to find and categorize all the microbes in the samples. Importantly, these researchers identified four different groups of patients based on the types and amounts of microbes in their lungs, helping them predict which children were more likely to suffer severe lung injuries, including lung infections.

Bone marrow transplants can be life-saving interventions for children with leukemia, bone marrow failure, and genetic disorders like SDS. However, the process of BMT involves strong chemotherapy that weakens the immune system and makes these individuals highly susceptible to infections. Unfortunately, these infections can be deadly, especially when patients need ventilators. Traditional tests may miss some pathogens (like bacteria and viruses) that cause these infections after BMT, but mNGS can identify a wide range of microscopic organisms, including rare ones, enabling more accurate treatments and improve outcomes.

By analyzing the mNGS data of these microscopic organisms in the lung microbiome of bone marrow transplant patients, the researchers discovered that patients in the group with the highest risk of death after bone marrow transplant not only had fewer types of microbes in their microbiome, but also had more Staphylococcus bacteria and viruses. This research suggests that a balanced lung microbiome is crucial for better bone marrow transplant outcomes.

For children with Shwachman-Diamond Syndrome (SDS), who are prone to infections and often need bone marrow transplants, these findings are especially important. Understanding the lung microbiome could help doctors better predict and treat infections in these patients. Using mNGS could lead to more precise treatments, improving survival rates for SDS patients undergoing transplants by allowing doctors to quickly identify and address the specific microbes causing infections after bone marrow transplant.

The SDS & Science Snapshot this week contains content modified from materials in this blog post, Lung Microbiomes Predict Mortality in Children Following Bone Marrow Transplant, published the Chan Zuckerburg Biohub Network.

Zinter MS, Dvorak CC, Mayday MY, Reyes G, Simon MR, Pearce EM, Kim H, Shaw PJ, Rowan CM, Auletta JJ, Martin PL, Godder K, Duncan CN, Lalefar NR, Kreml EM, Hume JR, Abdel-Azim H, Hurley C, Cuvelier GDE, Keating AK, Qayed M, Killinger JS, Fitzgerald JC, Hanna R, Mahadeo KM, Quigg TC, Satwani P, Castillo P, Gertz SJ, Moore TB, Hanisch B, Abdel-Mageed A, Phelan R, Davis DB, Hudspeth MP, Yanik GA, Pulsipher MA, Sulaiman I, Segal LN, Versluys BA, Lindemans CA, Boelens JJ, DeRisi JL.

Pediatric Transplantation and Cell Therapy Consortium. Pathobiological signatures of dysbiotic lung injury in pediatric patients undergoing stem cell transplantation. Nat Med. 2024 May 23. PMID: 38783139.  

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Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

Ask an Expert Recap: The Difference between Germline and Somatic Genetic Testing

At the most recent Ask an Expert webinar in May (see below), we heard from Dr. Lisa J. McReynolds, one of the newest members of the SDS Alliance Medical and Scientific Advisory Board (you can read her biography and more about her work here and welcome to the SDS Alliance community, Dr. McReynolds!). In this meeting, one of the topics discussed was the importance of diagnostic genetic testing for individuals with SDS and how hereditary (germline) variants (or mutations) are different from somatic mutations detected in cancerous (or pre-cancerous) cells, also known as clones. In our SDS & Science Snapshot this week, we will discuss the difference between these two mutation types (and how they are tested for) in more detail.

In the world of cancer, there are two main types of genetic tests that are used to inform care: germline genetic testing and somatic tumor (genomic) testing. Understanding the difference between these two types of mutations can be helpful in navigating the complexities of SDS. In a previous SDS & Science Snapshot, we discussed the difference between germline and somatic variants (or mutations). 

The figure below compares germline genetic testing and somatic genomic tumor testing. Sometimes in the clinic, somatic genomic tumor testing is also referred to as “NGS” (which stands for “next-generation sequencing”) and is frequently performed on the bone marrow biopsy samples from patients with SDS as discussed below.

While the results of these two types of genetic testing often look similar, there are a few key differences in the somatic genomic tumor testing to look out for:

• Variant allele frequency (VAF): This is how often the variant (or variants) were seen in the tested sample of cancerous (or pre-cancerous) cells. VAF provides insights to how predominant the variant (or variants) may be in the tumor sample. Knowing the VAF of somatic variants detected in a bone marrow biopsy sample can help your care team monitor for the development of MDS or AML or give insight into how someone with MDS or AML is responding to treatment.

  • Key difference: Sometimes germline variants can be identified on somatic genomic testing, but the VAF of germline genetic variants is typically around 50% and, if detected, are generally expected to remain constant across multiple somatic genomic tests. This is in comparison to the VAFs of somatic mutations, which change over time as the clones of cancerous cells develop and evolve over time. 

• Genes: Some genes are more commonly altered in pre-cancerous or cancerous cells than others. For example, TP53 variants are frequently seen in the bone marrow samples of individuals with MDS or AML, but most of those individuals do not have a germline TP53 variant, or Li Fraumeni Syndrome. Other examples of genes commonly mutated in the bone marrow samples of individuals with MDS or AML include DNMT3A, TET2, CSF3R, SF3B1, IDH1/2, RUNX1, and GATA2.

• Report Comments: Somatic genomic tumor testing (or NGS) are not meant to detect germline variants. If there is concern for the accidental detection of a germline variant that may play a role in a patient’s care plan, there will often be a comment about this in the NGS report. 

For more information regarding the development of clones and the difference between somatic and germline variants, you can watch this educational video on the genetics of SDS. We cover the concept of germline versus somatic variants (around minute 5), and how they relate to leukemia. You might also find it helpful to watch the recording of the Ask an Expert webinar with Dr. Lisa J. McReynolds above.

We encourage you to ask your healthcare provider about any questions you have about any genetic testing results, germline or somatic, and how these are used to manage care.

For more information regarding the difference between somatic and germline variants, you can visit the Cleveland Clinic’s website.

The SDS & Science Snapshot this week contains content modified from materials in this blog post, Tumor Genetics: Somatic vs Hereditary, published by Quest Diagnostics.

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Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

New Publication Combines Protein and Genetic Analyses to Help Diagnose Individuals with SDS

The process of identifying the genetic mutations responsible for an individual's diagnosis of Shwachman-Diamond Syndrome (SDS) can be complex, time-consuming, difficult to access, and expensive, especially when genetic tests don’t find the typical mutations. This is where exciting new fields called proteomics and proteogenomics can be helpful! In this SDS & Science Snapshot, we will highlight a new publication of a proteogenomic study in individuals with SDS and other inherited bone marrow failure syndromes which may help establish a new faster and cheaper way to screen for SDS before (or after) completing genetic testing!

Proteomics is the study of proteins in our bodies. Proteins are like tiny machines that do all sorts of important jobs, like building tissues and fighting off infections. By looking at the quantity and quality of all the proteins in a person’s cells, scientists can uncover differences in proteins that are responsible for disease (and might also help provide hints as to what genes to analyze in genetic testing). Proteogenomics combines proteomics with genomics, the study of genes. This means scientists look at both the genes and the proteins to get a complete picture of what’s happening at the cellular level. The video below published by the National Cancer Institute describes proteomics and proteogenomics and how these methods may be particularly helpful in treating cancer, but the same concepts can generally apply to SDS as well.

For people with SDS, proteomics and proteogenomics could be very useful. Even if a genetic test doesn’t show the usual SDS mutations, these new technologies can look at a different angle to help find changes in protein levels or protein interactions, which might reveal hidden problems that genetic tests miss. For example, if a person with SDS has unusual protein patterns, doctors might be able to spot this and diagnose SDS earlier. Since genetic testing is frequently complicated by the SBDS pseudogene (as reviewed in this previous SDS & Science Snapshot), these new types of analyses for individuals with mutations in the SBDS gene may be especially helpful in serving as a screening mechanism, signaling to a patient’s care team to keep searching for genetic mutations.

Using samples from individuals with inherited bone marrow syndromes, including SDS, researchers from Japan were able to test a new type of proteogenomic analysis to help screen for individuals with SDS based on the amount of SBDS protein in a patient's cells. These researchers found that individuals with low amounts of SBDS protein in blood also had mutations in the SBDS gene as revealed by genetic testing. By combining proteomics and genomics, some abnormal results in this study also helped lead researchers to using a different type of genetic testing to definitively identify SBDS mutations and provide a SDS diagnosis for two patients!

To the best of our knowledge, this was the first time that a simple, rapid screening test has been developed for diagnosing SDS. The authors suggest this type of proteomic-based diagnostic pathway could be easily and rapidly used across a large number of samples, leading to early identification of SDS and therapeutic intervention. These findings are encouraging and important for reducing the burden of the diagnostic odyssey for individuals with SDS. More research is still required to validate these types of proteomic and proteogenomic diagnostic methods, especially for those with genetic mutations in more rare SDS genes such as DNAJC21, EFL1, and SRP54. 

Wakamatsu M, Muramatsu H, Sato H, Ishikawa M, Konno R, Nakajima D, Hamada M, Okuno Y, Kawashima Y, Hama A, Ito M, Iwafuchi H, Takahashi Y, Ohara O.

Integrated proteogenomic analysis for inherited bone marrow failure syndrome. Leukemia. 2024 May 13. doi: 10.1038/s41375-024-02263-1. Epub ahead of print. PMID: 38740980.

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Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

The Genetic Landscape of Inherited Neutropenia in the Israeli Inherited Bone Marrow Failure Registry

In a study recently published in April, researchers investigated the genetic landscape of inherited neutropenia within the Israeli population. As many individuals in the Shwachman-Diamond Syndrome (SDS) community are familiar, neutropenia is characterized by abnormally low levels of neutrophils (a type of white blood cell which plays an important role in the immune system) and can leave individuals vulnerable to recurrent infections and other health complications. This new study, conducted with participants from the Israeli Inherited Bone Marrow Failure Registry, shed light on the genetic cause of inherited neutropenia in Israel, offering hope for improved diagnosis and management strategies.

Out of the 65 individuals with inherited neutropenia enrolled in the Israeli Inherited Bone Marrow Failure Registry, 74% received a genetic diagnosis. As pictured below, the most common forms of inherited neutropenia identified were ELANE neutropenia and G6PC3-severe congenital neutropenia. Interestingly, diagnoses of SDS and SDS-like syndromes were the third and fourth most common cause of inherited neutropenia in the Israeli Inherited Bone Marrow Failure Syndrome study with more than 25% of individuals having variants identified in the SBDS and SRP54 genes.

Among those with positive genetic testing, 15% had two mutations (or variants) detected in the SBDS gene. These individuals, primarily of Jewish or Arab Muslim descent, presented with a spectrum of common SDS symptoms, including pancreatic insufficiency, severe infections, and skeletal abnormalities.

Interestingly, around 12% of individuals with positive genetic testing had one mutation identified in the SRP54 gene, reported to cause an SDS-like syndrome. These individuals (even individuals within the same family) displayed a range of symptoms, including a few with mild, resolving exocrine pancreatic insufficiency and failure to thrive, reminiscent of SDS caused by SBDS mutations. When we reached out to Dr. Steinberg-Shemer, she highlighted that patients with SRP54 in Israel actually had isolated neutropenia with no significant pancreatic insufficiency.

For more information about the symptoms and genetic cause of SDS, you can watch the video below.

Importantly, the study reported that while none of the participants with SDS or SDS-like syndromes had been diagnosed with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), one individual successfully underwent a bone marrow transplant due to bone marrow failure. However, the authors of this study emphasized the importance of participating in regular bone marrow surveillance for those with SDS diagnoses.

These findings show the importance of participating in genetic testing for individuals with chronic neutropenia and frequent infections, especially for those at a young age. By identifying the genetic cause behind inherited neutropenia conditions, healthcare teams can tailor disease management strategies such as regular bone marrow surveillance for those with SDS. As we were reminded in last week’s SDS & Science Snapshot, understanding the genetic landscape of SDS and SDS-like syndromes in diverse populations, like in this Israeli cohort, is crucial for advocating for improved treatments and outcomes for individuals with SDS and SDS-like syndromes worldwide.

For more information regarding the clinical presentation of SDS and flyers about SDS to share with your care team, you can visit our “What is SDS?” page.

Disclaimer: The information contained in this blog post is an overview of published research and is not intended to be medical advice. If you are concerned you, or a loved one, has SDS, please contact your healthcare team.

Yeshareem L, Yacobovich J, Lebel A, Noy-Lotan S, Dgany O, Krasnov T, Berger Pinto G, Oniashvili N, Mardoukh J, Bielorai B, Laor R, Mandel-Shorer N, Ben Barak A, Levin C, Asleh M, Miskin H, Revel-Vilk S, Levin D, Benish M, Zuckerman T, Wolach O, Pazgal I, Brik Simon D, Gilad O, Yanir AD, Goldberg TA, Izraeli S, Tamary H, Steinberg-Shemer O.

Genetic backgrounds and clinical characteristics of congenital neutropenias in Israel. Eur J Haematol. 2024 Apr 11. doi: 10.1111/ejh.14197. Epub ahead of print. PMID: 38600884.

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Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

New Publication Highlights the Symptoms of SDS in China

In April, a new scientific article was published reviewing the symptoms of Shwachman-Diamond Syndrome (SDS) within the Chinese population, shedding light on this rare disease. As you may know, SDS is characterized by various symptoms like low blood cell counts, gastrointestinal problems (for example, chronic diarrhea/steatorrhea as a result of pancreatic insufficiency), developmental delays, skeletal abnormalities, and frequent infections. With this in mind, the authors of this publication found that SDS presents similarly in individuals from China as in other parts of the world. Not uncommon to the rare disease community, this study also found that about half of those with SDS faced delays in diagnosis (more than 2 years!), showing a need for greater awareness among healthcare providers, especially pediatricians in China.

This publication revealed that the most common symptoms at diagnosis in individuals with SDS in China included low blood counts (also known as cytopenia) and chronic diarrhea, while other issues like short stature and skeletal abnormalities were also common. Interestingly, while the gastrointestinal symptoms of pancreatic insufficiency tended to improve over time, low blood cell counts continued over time, which aligns with existing knowledge about the symptoms of SDS.

The authors of this article also reviewed the genetic testing results of individuals with SDS in China and they found most individuals with SDS carried the two most common variants mutations (or variants) in the SBDS gene (c.258+2T>C and c.183_184TA>CT) with other genetic mutations in the SBDS gene being more rare. Interestingly, there was one report of an individual with a mutation in the SRP54, which causes a so-called SDS-like syndrome and is inherited in an autosomal dominant pattern. For more information about the symptoms and genetic cause of SDS, check out the video below.

Moving forward, the authors of this publication advocate for a collaborative approach to managing SDS (as discussed in this previous SDS & Science Snapshot and pictured below), emphasizing the need for early diagnosis and proactive monitoring for potential complications like MDS and AML. Interestingly, MDS and AML were rarely reported in the Chinese SDS community, but the authors suggested this was because of a general lack of understanding and awareness about SDS amongst healthcare providers in China (one case report of an individual with SDS and AML in China was recently reviewed in this SDS & Science Snapshot).

This publication holds particular significance as it coincides with Asian American and Pacific Islander Heritage Month in the United States and serves as a reminder of the importance of understanding and advocating for individuals with SDS all over the world. At SDS Alliance, we recognize that our community is diverse, and we are committed to engaging with our global community to accelerate progress towards improved treatments and outcomes with SDS across the world.

For more information regarding the clinical presentation of SDS and flyers about SDS to share with your care team, you can visit our “What is SDS?” page.

Disclaimer: The information contained in this blog post is an overview of published research and is not intended to be medical advice. If you are concerned you, or a loved one, has SDS, please contact your healthcare team.

Clinical and genetic characteristics of Chinese patients with Shwachman Diamond syndrome: a literature review of Chinese publication.

Wang L, Jin Y, Chen Y, Zhao P, Shang X, Liu H, Sun L. Exp Biol Med (Maywood). 2024 Apr 8;249:10035. doi: 10.3389/ebm.2024.10035. PMID: 38651168.

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Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

New Study Publishes Custom Growth Charts for Individuals with SDS from Childhood to Adulthood

You've probably seen growth charts at the doctor's office or in a medical record — they track how kids grow over time, comparing their height and weight to others their age. But for some, like those with Shwachman-Diamond Syndrome (SDS), those charts might not tell the whole story.

As we know, SDS is a complex disorder affecting many systems. The majority of individuals with SDS have some degree of exocrine pancreatic insufficiency. This can lead to problems with digesting food and getting the right nutrients, which can cause them not to grow as much as other kids. Other common symptoms of SDS include failure to thrive and skeletal abnormalities, which also impact an individual’s growth and development compared to someone without SDS. So, using regular growth charts can be misleading for someone with SDS because their growth might not match what's expected for their age group.

That's why custom (or disease/population specific) growth charts are so important for people with SDS. These growth charts are made just for them, considering their unique needs and challenges. Unlike regular growth charts, which might suggest they're not growing well, personalized growth charts give a clearer picture of how they're doing. Until recently, custom growth charts were only available to individuals with SDS from 0 to 8 years of age. earlier this month, researchers in Italy published custom growth charts created for individuals with SDS from 0 to 18 years of age! These growth charts (pictured below) for height (a-b), weight (c-d), and BMI (e-f) were created from a large cohort of 121 individuals with SDS and over 700 growth measurements for both males (left panel) and females (right panel).

Growth charts for males (left) and females (right) with SDS for height (a-b), weight (c-d),

and body mass index (BMI; e-f) of patients with SDS from ages 0 to 18 years.

These researchers found that the 50th and 3rd percentiles of weight and height of the pediatric general population corresponds to the 97th and 50th percentiles of patients with SDS aged 0-18 years, respectively. In other words, if a child with SDS weighs in at about the 3rd percentile on the generic growth chart, that would correspond to the 50th percentile on the SDS growth chart. This could then be interpreted as the child doing well, right on target/average in terms of their weight compared to other children who also have SDS. Of course, families are encouraged to discuss such interpretations and all treatments with their health care team. This finding is an example of how using regular growth charts can be misleading for someone with SDS because their growth might not match what's expected for their age group.

Personalized growth charts for SDS not only help you to understand how individuals with SDS are growing, but it can also help doctors track how well treatments are working. For example, if someone with SDS tries a new medicine or therapy, this growth chart for individuals with SDS can show if it's helping them grow stronger and healthier.

These growth charts also help families understand their child's growth better, from 0 to 18 years. Instead of feeling confused by the numbers, you can see how your loved one is doing compared to others with SDS. This can help you feel more confident in managing your loved one’s health and making decisions about their care.

We encourage you to share this publication and these growth charts with your healthcare team to see how they can help you in your journey with SDS!

Pegoraro A, Bezzerri V, Tridello G, Brignole C, Lucca F, Pintani E, Danesino C, Cesaro S, Fioredda F, Cipolli M. Growth Charts for Shwachman-Diamond Syndrome at Ages 0 to 18 Years. Cancers (Basel). 2024 Apr 5;16(7):1420. doi: 10.3390/cancers16071420. PMID: 38611098.

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Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

What is EuNet-INNOCHRON?

EuNet-INNOCHRON is an ACTION OF EUROPEAN COOPERATION IN SCIENCE AND TECHNOLOGY, and is an abbreviation for European Network for Innovative Diagnosis and Treatment of Chronic Neutropenias.

Chronic neutropenias (CNP) represent a wide spectrum of disorders ranging from mild to life-threatening, acquired or congenital diseases. Shwachman-Diamond Syndrome is part of this category, specifically part of the congenital neutropenia subtype.

The pathophysiological mechanisms underlying CNPs are diverse and vary from haemopoietic stem cell and bone marrow microenvironment defects resulting in impaired neutrophil production, to immune disturbances leading to accelerated apoptosis of neutrophil progenitors and/or the circulating mature neutrophils. The prognosis of patients with CNP is related to the underlying pathogenesis, the degree of neutropenia and the propensity for leukaemic transformation.

Accurate diagnosis is mandatory for risk stratification and treatment choice.

The principal challenge of the Action is to establish a wide network of researchers with special interest in CNPs and facilitate interactions and collaborations among top-level European experts and young investigators from different scientific areas i.e. Clinical and Laboratory Haematology, Immunology, Genetics, Molecular Biology and Regenerative Medicine.

The main aims of the Action are:

1. to promote science, training and education on advanced biochemical, immunological, genetic and molecular biology techniques for the accurate diagnosis and treatment of patients with different types of CNP, early recognition of Myelodysplastic Syndromes/Acute Myeloid Lekaemia evolution and appropriate intervention,

2. to link and further expand existing neutropenia networks for a more multidisciplinary approach of CNP that will result in a better characterization of the underlying diseases and development of individualized and precision medicine therapeutic approaches for selected patients,

3. to organize and expand CNP patient Registries and Biobanks using homogenized protocols in line with the ethical standards of the European Legal Framework and the relevant national regulations.

How did the SDS Alliance highlight the patient voice?

The SDS Alliance was invited to present the patient perspective and our advocacy efforts, and the organizers were very accommodating by providing virtual access to this impactful in-person meeting. Dr. Hars focused her talk on two areas. First, she shared patient stories and the impact SDS has on patients and their families. Second, she highlighted the SDS Alliance's programs to accelerate research toward therapies and cures. These focus areas and their progress are also highlighted on our website on our Strategy & Roadmap page.

What was the Final Conference and Working group meeting about?

The Final Conference of EuNET-INNOCHRON (European Network for the Innovative Diagnosis and Treatment of Chronic Neutropenias) Research Newtork - a COST Action - focusing on research in the field of chronic neutropenias, took place April 4-6, 2024 at the KAM Center of Mediterranean Architecture in Chania, with limited virtual access to selected speakers.

The chair of the COST Action CA18233 EuNet-INNOCHRON, Helen Papadaki, Professor of

Hematology School of Medicine, University of Crete and Director of the Hematology Department of the University Hospital of Heraklion UHH (PAGNI), organized the conference, with the participation of researchers from 32 countries as well as the European Hematology Association (EHA). Ninenty (90) researchers from 22 countries participated onsite at the final conference.

The goal of the conference was to discuss and present the results of the research of the four-year Action in the field of neutropenias - in children and adults alike - the prevention of its progression into acute leukemia, to highlight the recent focus areas which have emerged and the prospects of continuing the existing collaborations and research between partners of the Action.

During the conference, young investigators had the opportunity to present their recent results on their work in the field of neutropenias, discuss with experts in the field, expand their scientific network and promote further collaborations between research Institutions and hospitals across Europe.

Particularly important is the Common EU Guidelines on the diagnosis and Management of

Neutropenia jointly published by EUNET-INNOCHRON and the European Hematology Association, for the benefit of patients, their families and caretakers and practicing clinicians.

This publication focuses on neutropenia overall, and only touches on SDS superficially. However, it encourages genetic testing to include SDS and other genetic causes of neutropenia and references other important articles.

Patient representatives were also present and provided their perspectives, helping redefine therapeutic goals while providing insights on their expectations.

On behalf of the SDS patient and advocacy community, the SDS Alliance would like to express our sincere gratitude for the opportunity to participate in this important action, community, and meeting.

Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

An exploration of the experiences of siblings of people with a diagnosis of Shwachman-Diamond Syndrome

Living with a sibling who has a rare disease like Shwachman-Diamond Syndrome (SDS) can be a complex experience for the unaffected sibling(s). While they may not have the same physical symptoms or medical needs, the emotional impact can be significant and often introduce unique challenges to the family dynamic. Despite not having SDS themselves, the unaffected sibling's life is inevitably shaped by its presence, leading to a complex mix of emotions that require understanding and support from those around them. Other studies investigating the experience of siblings to individuals with inherited bone marrow failure syndromes such as Fanconi anemia have been published, but the experience of unaffected siblings to those with SDS have not been specifically explored… until now! 

In our SDS & Science Snapshot this week, we are happy to share a new research opportunity exploring the experiences of siblings to individuals with SDS. This study is being led by Amy Doyle, a family therapy trainee at the University of Exeter in England, United Kingdom.

Here is what Amy, the lead researcher, shared about the importance of this study and how to get involved:

What is the purpose of this study?

The aim for this study is to learn more about the experiences of siblings to individuals with SDS from childhood to adulthood and to highlight the potential value in and usefulness of additional support such as therapy for families of people experiencing SDS.

What is your inspiration for leading this study?

I have an interest in and awareness of SDS due to a personal, family connection. In reviewing the current research and learning more about other chronic illnesses, I have recognized that the majority of support that is currently available is for affected individuals. I recognize and am learning that conditions like SDS have an impact on the whole family system and hope that this study can provide insight on this experience.

Who is eligible to participate?

Individuals who meet the following criteria are eligible to participate:

• Siblings to individuals with a diagnosis of SDS

• Adult participants at least 18 years of age

• Must be able to speak English

• Access to a computer, internet, and video-conferencing 

How is this study being conducted?

Participants will be asked to answer a brief demographic survey online with questions about age, gender, ethnicity, geographical location, and education level. Following this survey, the lead researcher will conduct individual interviews online via Microsoft Teams. It is anticipated that the interviews will take no longer than one hour. These interviews will be recorded and transcribed by the lead researcher. The interview transcripts will be anonymised and analyzed.

What kind of questions will be asked?

Questions asked of participants will be particularly centered around individuals’ experiences as siblings, and to explore the impact that SDS has had on their lives as individuals and as a family. Questions will also consider the support that has been offered and is available, as well as what may or may not have been helpful for them and their families.

What will happen to the results of this research study?

The results of this research study will be analyzed and written up as part of the lead researcher’s final dissertation project. The lead researcher hopes to present the results of this study to the trustees of the Shwachman-Diamond Syndrome UK charity and potentially publish the results in a relevant journal.

Who is overseeing this research?

This research is being conducted as part of the lead researcher’s final dissertation at the University of Exeter. The researcher’s tutor Kate Campbell is overseeing the research.

The Data Controller for this research is the University of Exeter. Ethical approval for this research has been granted by the University of Exeter’s CEDAR psychology ethics committee.

How do I get involved?

If you are eligible or know someone who is, please don't hesitate to get in touch with me by emailing me at ad903@exeter.ac.uk. I can share my participant information sheet with you and answer any questions that you have.

Resources for Siblings to Individuals with a Rare Disease:

• The Sibling Support Project: https://siblingsupport.org/

• Sibling Leadership Network: https://siblingleadership.org/

• Rare Sibling Stories: https://linktr.ee/raresiblingstories

Stay tuned to our SDS & Science Snapshot series next week to learn more about a new study which published growth charts specific for individuals with SDS!

Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

The Importance of Germline Genetic Testing for Patients with Bone Marrow Failure and Related Disorders

Between March 21-22, 2024, the Aplastic Anemia and Myelodysplastic Syndrome International Foundation (AAMDSIF) hosted the 9th International Bone Marrow Failure Disease Scientific Symposium in Bethesda, MD, USA. This meeting brought together experts from around the world to discuss the latest advances in both the science and patient care for these disorders. The first session at the Scientific Symposium highlighted the role of genetic testing for persons with bone marrow failure, and led to a lively discussion on when, whom, and what genetic testing should be offered.

We reached out to Dr. Lisa J. McReynolds, a leading physician-scientist studying inherited bone marrow failure syndromes (including Shwachman-Diamond Syndrome!) and the first speaker at this Scientific Symposium, to bring you an exclusive summary of their thoughts on the importance of genetic testing for individuals with bone marrow failure.

Here is what they shared:

Shwachman-Diamond Syndrome (SDS) is part of a group of disorders that are often collectively called “inherited bone marrow failure syndromes (IBMFS).” This is because what unites all IBMFS is that they can be genetic (or inherited, passed from parent to child in the genes) and can cause a person’s bone marrow to “fail”, stop working, or malfunction. It can be very difficult to sort out which form of bone marrow failure a person has. This problem is made worse by the fact that other disorders that are not genetic can look a lot like an IBMFS. Two of these disorders are aplastic anemia (AA) and myelodysplastic syndrome (MDS). AA is caused by an immune attack on the person’s bone marrow leading to it to not function. MDS is a form of blood cancer that under the microscope can look like an IBMFS.

There are some laboratory tests that can help sort out IBMFS (and which specific type) versus AA versus MDS, but they can be insufficient to get a final diagnosis. One of the best tools healthcare providers have to reach an accurate diagnosis is genetic testing.

This SDS & Science Snapshot published last fall helps explain the role of genes in developing diseases such as AA or MDS and the difference between somatic and germline mutations. Additionally, the SDS Science Spotlight YouTube video below also explains how individuals with SDS are at-risk of developing bone marrow failure or leukemia and how this relates to the genetics of SDS.

So, why should people with bone marrow failure, such as individuals with SDS, have genetic testing? 

1. The signs of a genetic disorder can be subtle or absent when a person comes to the attention of a healthcare provider, and there is often no family history of a genetic disease. 

2. About 5% of all patients with bone marrow failure have a genetic reason for their disease. This number is critical since many professional societies recommend genetic testing for diseases with a greater than 5% chance of being genetic.

3. Uncovering a genetic cause for the person with bone marrow failure can lead to changes in treatment planning and screening recommendations moving forward.

4. Genetic testing results may also change who is chosen as a donor if the person plans to have a bone marrow transplant. 

5. Genetic testing results can also help guide potential genetic testing of other family members. 

There are several different types of genetic testing that can be done for SDS and other bone marrow failure diseases, such as panel testing or exome sequencing (this SDS & Science Snapshot published a few weeks ago reviews genetic testing for SDS in more detail). The choice of testing is best determined by your genetic counselor and physician. However, getting genetic testing can be challenging for some patients. One of the biggest challenges many patients face is insurance coverage. Many insurance companies do not cover the testing and if it is covered it can be insufficient or come with large out-of-pocket costs. This has unfortunately led to inequities across our bone marrow failure community with some patients being able to access genetic testing and others not. Healthcare providers need to advocate for all bone marrow failure patients to receive genetic testing as recommended.

To help address these inequities, Shwachman-Diamond Syndrome Alliance is committed to increasing access to no-cost clinical genetic testing for individuals suspected of having SDS and providing opportunities to participate in research for those with previous negative or uninformative genetic testing results. 

Stay tuned to our SDS & Science Snapshot series this Spring to learn more about genetic testing resources that may be helpful for your family! Or, reach out to us directly via email at genetics@SDSAlliance.org. We are here to help!

The team at SDS Alliance would like to extend a warm message of appreciation to Dr. Lisa J. McReynolds for their contributions to this SDS & Science Snapshot and, more importantly, for leading critical research efforts for individuals with IBMFS such as SDS!

AAMDSIF Resources: 

The AAMDSIF has published several Patient Guides and Fact Sheets (available in multiple languages including Italian, French, German, Spanish, and Portuguese!) for understanding acute myeloid leukemia (AML), MDS, and AA on their website!

These toolkits published by AAMDSIF answer some of your most important questions about Aplastic Anemia and Myelodysplastic Syndrome!

AAMDSIF also hosts Patient and Family Conferences for individuals who have been diagnosed with and/or survived AA, MDS, AML - visit their website for a list of these events happening this year across the United States in Los Angeles, Seattle, Philadelphia, Chicago, and Tampa.

Disclaimer: The views and opinions expressed in this SDS & Science Snapshot only reflect those of Lisa J. McReynolds, MD, PhD.

Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

BeginNGS: Newborn Genomic Sequencing to End the Diagnostic Odyssey

Two weeks ago, a new podcast episode of Once Upon a Gene was released highlighting BeginNGS, a ground-breaking initiative at Rady Children’s Institute for Genomic Medicine (RCIGM) that is helping to rewrite the story for infants with rare diseases (including Shwachman-Diamond Syndrome!).

We reached out to Dr. Jennifer Schleit, Laboratory Director at RCIGM, to bring you an exclusive summary on how advances in genetic testing technology are changing newborn screening methods and the course of the diagnostic odyssey in rare disease.

Here is what they shared:

Newborn screening (NBS) is a public health program aimed at testing babies for genetic conditions that are treatable, but may not be apparent at birth. Through early diagnosis, affected children can receive appropriate monitoring and treatments to reduce the negative impacts of these disorders and improve survival rates. (For more information about the economic impact of a delayed diagnosis, you can read this recent SDS & Science Snapshot). Currently, NBS programs are active in all 50 states and it is estimated that approximately 98% of babies born in the United States will be tested in the first two days of life. An interactive timeline showing the evolution of newborn screening methods is published on the BeginNGS website.

For more information about traditional newborn screening and what conditions are screened for across the United States, you can visit this website, Baby’s First Test.

How are advances in genetic testing technology changing newborn screening?

Current NBS programs primarily use laboratory methods such as mass spectrometry or enzyme activity to perform the screening in babies These methods have been successful, however they limit the number of disorders that can be tested, as only those disorders that can be detected with these testing methods can be included in current screening programs. Recent advances in genome sequencing, including reduced sequencing costs and faster sequencing time, have led to this technology being considered as a new testing method in NBS. Genome sequencing allows for more disorders to be tested simultaneously.

The SDS & Science Snapshot published a few weeks ago helps explain why genetic testing for SDS is important and how you can access it.

What is BeginNGS?

BeginNGS is a pilot project based out of Rady Children’s Institute for Genomic Medicine (RCIGM) to use genome sequencing to screen newborns for over 400 early onset, actionable disorders (including Shwachman-Diamond Syndrome!). RCIGM is a world leader in ultra-rapid and rapid genome testing, making it uniquely positioned to deliver NBS results in a timely manner. This project is currently based at Rady’s Children’s Hospital in San Diego, California. The BeginNGS team is actively planning to expand this trial to include additional health systems to enable participation from more geographic areas.

How are disorders selected or BeginNGS?

Candidate disorders were identified by reviewing clinical diagnostic testing of over 4000 critically ill newborns and children at RCIGM, by reviewing lists of expanded NBS disorder lists developed by other groups, and by evaluating publications which reported interventions for these disorders. Selected disorders were then evaluated by a team of medical and genetics professionals. Disorders included in BeginNGS met the following criteria:

• They had acute, childhood admission that were likely to lead to hospital admission

• A treatment was available for the disorder

• It is a single-locus genetic disorder, inherited defects in a single gene can cause disease

• There is a high likelihood of rapid disease progression without treatment

• The disorder can be diagnosed by genome sequencing

Additional disorders could be added to BeginNGS as they are discovered and/or new treatments become available.

The team at SDS Alliance would like to extend a warm message of appreciation to Dr. Jennifer Schleit and the BeginNGS team for blazing trails in the newborn genomic sequencing space, shortening the diagnostic odyssey for individuals and families in the SDS community.

SDS Alliance looks forward to sharing the results of the BeginNGS initiative with the SDS community in future SDS & Science Snapshots.

For more detailed information about how Rady Children’s Institute for Genomic Medicine plans to change the landscape of newborn screening with whole genome sequencing, you can read their manuscript published in the American Journal of Medical Genetics.

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Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

The last few weeks have brought us three different case reports published in the biomedical literature, each highlighting a different aspect of the disease.

A case report of a young patient with SDS whose diagnosis was nearly missed

This case report shares the story of a young patient with SDS whose diagnosis was nearly missed due to inconsistent genetic test results and liver issues not always recognized as typical for SDS.

Initially, the patient was thought to have a rare, genetic liver disease or mitochondrial disease. The authors describe in great detail their findings regarding the liver of the patient, such as electron microscopy imaging of the inside structure of liver cells, including mitochondria. Note, that the ribosomes in the mitochondria (a.k.a. mitoribosomes) are structurally different and responsible for translating genetic information encoded in mitochondrial DNA. These ribosomes are NOT involved in SDS, but can cause mitochondrial diseases if there is a defect. Mitochondria are organelles responsible for converting energy from food into ATP, the chemical energy our cells need to live and thrive. Check out our blog post on ribosomes and mitochondria, here. The authors report:

As we all know, SDS is a rare genetic syndrome characterized by multiorgan dysfunction with typical presenting features that include exocrine pancreatic, hematologic, and skeletal abnormalities. It is now also established that the liver is often affected. However, the long-term implications are not known, and there is no treatment available for the frequently reported highly elevated liver enzymes (transaminases) in young children. We know from the SDS patient community that many patients undergo liver biopsy before being diagnosed with SDS, with no clinically actionable outcomes. For most patients, the liver enzyme levels go back down into (or close to) normal levels within the first 5 years of life. The authors report:

We believe that this assumption warrants further investigation, as there is very little data available about adult SDS patients' overall health. Despite the high prevalence of highly elevated liver enzymes in early childhood, very little is known about the condition. There is a high need for research in this area.

The genetic workup of the child has not been straightforward, either. Whole exome sequencing (WES) initially missed the diagnosis. The authors looked into why. They think that it is either because not all the relevant symptoms were listed in the WES test request, and therefore the SDS genes may not have received the proper attention at the data interpretation step by the testing company, or perhaps there was a problem with the test analytics due to the SBDS pseudogene SBDSP1. Check out our blog post on pseudogenes to learn more. The authors report:

The full article is available here:

A success story of treating an SDS patient with AML in China

One of the biggest concerns we face as SDS patients and caregivers is the risk of developing leukemia, specifically acute myeloid leukemia, or AML for short. The risk is estimated to be around 30% by age 30, which keeps on going up after that. AML develops when the blood-forming stem cells in the bone marrow accumulate new mutations (also known as somatic mutations) that allow them to grow out of control. We have covered the mechanism of this in an educational video, here.

To make matters worse, AML in SDS patients often contains p53 mutations, which makes its treatment even harder than it already is. Combined with the increased sensitivity to chemotherapy that would be needed to get rid of AML, there are very few success stories of a positive outcome.

The medical and scientific community is hard at work trying to find better treatment options for AML, for both the general population and for SDS patients, as highlighted at many scientific conferences, including the AA-MDS Symposium which our team attended just last week. More about that soon.

Today, we want to highlight a brand new case report from Beijing, China, in which the authors report success in treating one SDS patient who developed AML. The approach was to treat the AML first to reduce the number of AML cells, in order to increase the likelihood of success for hematopoietic stem cell transplant. This is not a new approach, and many groups are looking for a good combination of chemotherapeutic drugs that can work for SDS. It seems that for this particular patient, they found something that worked. The authors report:

At the time of this article, the patient has been 6 months post-transplant and well. We wish the 15 year-old-patient continued health and recovery.

We have reached out to the authors to learn more and will update this blog post if new information becomes available.

Azacitidine combined with venetoclax alleviates AML-MR with TP53 mutation in SDS: a case report and literature review.

Ma C, Lang H, Chen Y, Yang L, Wang C, Han L, Chen X, Ma W.Anticancer Drugs. 2024 Mar 15. doi: 10.1097/CAD.0000000000001594. Online ahead of print.PMID: 38502829

A case of a severe, zoonic infection of a 17-year-old patient with SDS

In this recent case report, the authors share the case of a 17-year-old patient who was diagnosed with SDS as a child and treated with GCSF and PERT but lost to follow-up for several years. She came to the emergency room very ill with an acute infection, which developed into sepsis. The primary infection was identified as rat-bite fever (RBF), an important bacterial zoonosis primarily caused by Streptobacillus moniliformis in North America, but the pathogenesis is understudied.

From the information available to us about the article, it is unclear whether the patient made a full recovery or not. We have reached out to the authors to request more information and will update this blog post as we learn more.

If you or your child has SDS, please discuss with your healthcare team whether pets are safe for your household, and/or what special precautions should be taken around them. Frequent recommendations from the SDS community include being extra careful around cat litter and avoiding handing cat litter to SDS patients and any people who may be immune-compromised (such as pregnant people) to reduce the risks of toxoplasmosis.

Warning: there are disturbing images included in the original article. Viewer discretion is advised.

Oh rats! Intracellular rod-like inclusions in an adolescent with Shwachman-Diamond syndrome.

Mayhew J, Luttrell H, Barros K, Blazin L, Nichols C, Avashia-Khemka N, Lavik JP, Relich RF, Skinner D, Zhou J, Saraf A, Khaitan A.Pediatr Blood Cancer. 2024 May;71(5):e30918. doi: 10.1002/pbc.30918. Epub 2024 Feb 23.PMID: 38391125 No abstract available.

Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

Spring into Action: Genes and Genetic Testing for SDS

On Rare Disease Day two weeks ago, we launched our "Spring into Action" campaign, with which we amplify the patient voice in SDS in order to improve patients' lives, be it through more focused, impactful research, community support, or advocacy.

Over the next few weeks and months, we will highlight multiple efforts, resources, and learning opportunities. Today, we bring you a summary of genes, genetic testing, and the importance of both in SDS.

What are genes?

Our bodies are composed of trillions of cells that have many different roles – to help us grow, digest food, protect us against infections, and more. These different tasks are controlled by a set of instructions known as genes. (We even have genes whose purpose is to protect us against cancer!) Genes are made up of DNA, which you inherit from your parents, and they determine things like your eye color, height, and even your risk for certain health conditions.

What are genetic mutations (i.e., variants)?

Sometimes there are mistakes in our genes, like a typo or error in an instruction manual or recipe book. These genetic mistakes are called mutations or variants. Shwachman-Diamond Syndrome (SDS) happens because of these genetic mistakes in certain genes including SBDS, EFL1, DNAJC21, and SRP54. These genetic mistakes are passed down from parents to kids and cause SDS.

Imagine if a sentence in a recipe book had a mistake, like telling you to turn off the oven to bake cookies. Then the cookies wouldn’t bake properly! Our cells work the same way. If there's a mistake in the genes that tell our cells what to do, our cells may have a difficult time functioning properly.

You can also watch our SDS Science Spotlight video on the Genetics of SDS to hear more about how these genetic mistakes (or mutations) contribute to the development of SDS.

What is genetic testing?

Genetic testing is the process of analyzing a gene (or more commonly, a set of genes) for these genetic mistakes that would result in SDS. Genetic testing is comparable to reading an instruction manual or recipe book very closely to identify any errors made during the writing process.

Why is genetic testing for SDS important?

Genetic testing for SDS helps your care team confirm a diagnosis of SDS and provide a clearer understanding of why you may be experiencing certain health issues. A genetic diagnosis of SDS can help guide your care team in making and following personalized treatment plans and surveillance guidelines to help you stay healthy!

What types of genetic testing are recommended for individuals with symptoms of SDS?

There are different kinds of genetic testing available for individuals who have a suspicion for SDS based on symptoms or health issues and/or a family history of SDS.

If we return to the instruction manual analogy when considering the different types of genetic testing, there are some genetic tests that only look for errors in specific sections of the instruction manual known to be associated with SDS. This type of genetic testing only looks at one or all of the known SDS/SDS-like genes, including SBDS, EFL1, DNAJC21, and/or SRP54.

There are other more thorough types of genetic testing that look for errors in the entire instruction manual, meaning all of the genes in your cells (over 20,000!) are analyzed. This kind of genetic testing can be costly and time-consuming but may provide an answer for some families as we learn more about the genetic cause(s) of SDS.

My care team has mentioned their concern for SDS, how do I access genetic testing?

If your care team has mentioned a concern for SDS, we encourage you to talk with them about your options for genetic counseling and testing. Genetic testing can be ordered by a healthcare provider such as a doctor or a genetic counselor. In the SDS community, physicians who order genetic testing for SDS frequently include primary care physicians, pediatricians, gastroenterologists, hematologists, oncologists, and many others.

For individuals in the United States, The National Society of Genetic Counselors has a Find a Genetic Counselor Tool available on their website to search for a genetic counselor local to you. We encourage you to choose the specialties of Cancer, Hematology, and/or Pediatrics to help you narrow your search for a genetic counselor.

If I have SDS myself, and my partner doesn't, can our kids get SDS?

The odds of your children getting SDS depends on your and your partner's genetic makeup. For example, let's consider SDS caused by mutations in the SBDS gene, which typically is inherited in an autosomal recessive pattern. A partner who doesn't have symptoms of SDS may be a carrier of one mutation in a gene that causes SDS or have no mutation at all. The partner with SDS will have two mutated versions of the gene, and no healthy copy. The odds of the children getting SDS will depends on all these factors and more, such as rare genetic events related to pseudogenes, for example. Check out the video embedded above. We covered the concept of pseudogenes in an earlier edition of the snapshots, and these may factor into the odds as well.

If you have a diagnosis of SDS and/or a family history of SDS, and are planning a pregnancy, you may also find it helpful to speak with a Prenatal Genetic Counselor to discuss what genetic testing might be available to help inform you and your partner on the chances of having a baby who also has SDS. For individuals in the United States, The National Society of Genetic Counselors has a Find a Genetic Counselor Tool available on their website to search for a genetic counselor local to you.

Stay tuned to our Science Snapshot series this Spring to learn more about genetic testing resources that may be helpful for your family!

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Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

Welcome to our timely updates on all things SDS, Science, and Advocacy. We bring you a digest of recent scientific publications, conferences, and other newsworthy content - all relevant to SDS - with links to more details and learning opportunities. Are you interested in anything specific? Did we miss something? Let us know. Email genetics@SDSAlliance.org or message us on Facebook! This is all for you!

Spring into Action: Joyce's Rare Disease Day Experience

Every year, on the last day of February, the international Rare Disease Community comes together to raise awareness about important policy and other issues related to rare disease. For us, every day is Rare Disease Day. Check out our updated Rare Disease Day website.

Rare Disease Day, for us, is a launch pad for our "Spring into Action" campaign, with which we amplify the patient voice in SDS in order to improve patients' lives, be it through more focused, impactful research, community support, or advocacy.

Over the next few weeks and months, we will highlight multiple efforts on how the SDS community springs into action, starting with how our community leveraged Rare Disease Day events to learn and make progress.

Today, we bring you an interview with Joyce, a young advocate living with SDS, highlighting her Rare Disease Day experience. You can learn more about Joyce’s story of living with SDS on the Rare Disease Day website where she is featured as a hero or in this 60 Seconds of RARE video published by the RARE Revolutions Magazine.

What event(s) did you participate in for Rare Disease Day and what was your motivation to participate?

Joyce: On Rare Disease Day in 2024, I participated in the Rare Disease Legislative Advocates’ Annual Rare Disease Week on Capitol Hill. Over four days we attended conferences, caucus briefings, and discussions. On February 27th, everyone had meetings with their state senate offices and representatives to share their story and introduce legislation to help them in their journey. I was motivated to participate in this event not only because of my advocacy experience and public speaking skills, but also because I wanted to share my story to help assist and guide the government into making decisions that would benefit the rare disease community. I used my experiences and knowledge to my advantage to guide the minds of those in Congress to sign-off on key legislation that would impact the rare disease community.

What was your most memorable moment from Rare Disease Day?

My most memorable moment from Rare Disease Week was meeting others with rare diseases or connecting with rare diseases and advocating together. It was such an empowering moment to be able to connect with others who have experienced similar journeys – being together in one room to advocate for similar goals. We all were encouraging and standing with each other during our meetings and events to motivate ourselves and the people around us. I very much enjoyed being able to speak up about some issues involving the rare disease community and some possible legislation that would impact the SDS community.

Did you learn anything new or gain any insights from your participation in Rare Disease Day events?

I learned a lot this year on Rare Disease Week. I learned how to gain a stronger understanding of how to tell my story, and what details to share when speaking with government officials. I learned how I can incorporate my experience and journey with SDS into advocating for certain bills for the rare disease community as a whole. I gained insight from fellow peers, advocates, and leaders in the rare disease community about the diagnostic odyssey of rare disease patients and what each individual is doing to help us as a community. I learned how to transform my public speaking skills into a motivational day full of business and fun. Plus a fun little perk of attending this event is that I learned how to navigate my way through the US House of Representatives and Senate buildings through underground tunnels.

How do you plan to continue advocating for SDS and other rare diseases beyond Rare Disease Day?

I plan to continue to be an active member of the Rare Disease Legislative Advocates this year, speaking out for legislation for the rare disease community. This year I plan to be an active Young Adult Rare Representative as I enter my 16th year of life. I plan to continue to use my experience of living with a rare genetic disorder to further expand the knowledge of those around me about SDS and the problems surrounding our community. By using my story, I can have solid backing for my proposals to the congressmen and women, giving them a personal connection to the legislation. I also plan to continue to post on my SDS Instagram account @cure.sds, to provide information on the disease and what daily life looks like.

What advice would you give to others who are interested in getting involved in advocacy efforts for Rare Disease?

The advice I give to others is always to use their past experiences and traumas to their advantage in the field of advocacy. Use your insight and knowledge of living with or caring for someone with a rare condition to be able to speak up against the issues in the rare disease community. I always tell people they should not fear their disease and instead make it a part of them. In advocacy work, it is key to embrace your disorder to truly be able to speak out and stand up for what is right. By using your story, you can catch the eyes of people who may have never heard of your disorder and are willing to help. If you are just entering into the advocacy space, I recommend starting small, creating a social media platform to raise awareness and give insight into the common problems and daily life of living with a rare disorder. Never stop because something goes wrong, use that negative event as further inspiration to keep thriving as an advocate and as a human being. Not everything is going to go your way all the time, there will be some bumps in the road, so turn that negativity into strength.

On behalf of our team at SDS Alliance - Joyce, we thank you for your hard work, dedication, and passionate advocacy for the SDS community on Rare Disease Day and everyday! We are grateful to have you as a member of our community and can't wait to see how you transform the lives of so many living with a rare disease.

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Check out our new SDS infographics (available in English and Spanish/Español)!

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If you’re interested in viewing some of this year’s Rare Disease Day events, many of them were recorded and are now available to stream online:

• The White House: Rare Disease Forum

• Broad Institute of MIT and Harvard: Rare Disease Day 2024: Climbing Ladders to Cures in Rare Disease Research

• National Institutes of Health (NIH): Rare Disease Day Event

• US Food and Drug Administration (FDA): FDA's Rare Disease Day 2024—Dedicated to Patients and Providers

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Actúe: la experiencia del Día de las Enfermedades Raras de Joyce

En este número: Preguntas y respuestas con un defensor de SDS: ¿Qué estaban haciendo el Día de las Enfermedades Raras?

Cada año, en el último día de febrero, la comunidad internacional de enfermedades raras se reúne para crear conciencia sobre políticas importantes y otras cuestiones relacionadas con las enfermedades raras. Para nosotros, cada día es un día de Enfermedad Rara.

Para nosotros, el Día de las Enfermedades Raras es una plataforma de lanzamiento para nuestra campaña "Actúe en primavera", con la que amplificamos la voz de los pacientes en SDS para mejorar sus vidas, ya sea a través de investigaciones más enfocadas e impactantes, apoyo comunitario o abogacía.

Durante las próximas semanas y meses, destacaremos múltiples esfuerzos. Hoy les traemos un resumen de cómo nuestro equipo aprovechó los eventos del Día de las Enfermedades Raras para aprender y progresar. Le preguntamos a Joyce, una joven defensora que vive con SDS, sobre su experiencia en el Día de las Enfermedades Raras. Puede obtener más información sobre la historia de Joyce sobre cómo vivir con SDS en el sitio web del Día de las Enfermedades Raras, donde aparece como una heroína o en este video de 60 Seconds of RARE publicado por la revista RARE Revolutions.

¿En qué eventos participó para el Día de las Enfermedades Raras y cuál fue su motivación para participar?

Joyce: En el Día de las Enfermedades Raras de 2024, participé en la Semana Anual de Enfermedades Raras de los Defensores Legislativos de Enfermedades Raras en Capitol Hill. Durante cuatro días asistimos a conferencias, reuniones informativas y discusiones. El 27 de febrero, todos se reunieron con las oficinas y representantes del senado estatal para compartir su historia y presentar legislación que los ayude en su viaje. Me motivó a participar en este evento no solo por mi experiencia en defensa de derechos y mis habilidades para hablar en público, sino también porque quería compartir mi historia para ayudar y guiar al gobierno en la toma de decisiones que beneficiarían a la comunidad de enfermedades raras. Utilicé mis experiencias y conocimientos a mi favor para guiar las mentes de los miembros del Congreso para aprobar una legislación clave que afectaría a la comunidad de enfermedades raras.

¿Cuál fue tu momento más memorable del Día de las Enfermedades Raras?

Mi momento más memorable de la Semana de las Enfermedades Raras fue conocer a otras personas con enfermedades raras o conectarme con enfermedades raras y abogar juntos. Fue un momento muy enriquecedor poder conectarme con otras personas que han experimentado viajes similares: estar juntos en una sala para abogar por objetivos similares. Todos nos animamos y nos apoyamos unos a otros durante nuestras reuniones y eventos para motivarnos a nosotros mismos y a las personas que nos rodean. Disfruté mucho poder hablar sobre algunos temas que involucran a la comunidad de enfermedades raras y algunas posibles leyes que afectarían a la comunidad SDS.

¿Aprendió algo nuevo u obtuvo alguna información a partir de su participación en los eventos del Día de las Enfermedades Raras?

Aprendí mucho este año en la Semana de las Enfermedades Raras. Aprendí a comprender mejor cómo contar mi historia y qué detalles compartir al hablar con funcionarios del gobierno. Aprendí cómo puedo incorporar mi experiencia y mi trayectoria con SDS para defender ciertos proyectos de ley para la comunidad de enfermedades raras en su conjunto. Obtuve información de colegas, defensores y líderes de la comunidad de enfermedades raras sobre la odisea diagnóstica de los pacientes con enfermedades raras y lo que cada individuo está haciendo para ayudarnos como comunidad. Aprendí cómo transformar mis habilidades para hablar en público en un día motivador lleno de negocios y diversión. Además, una pequeña ventaja divertida de asistir a este evento es que aprendí a navegar a través de los edificios de la Cámara de Representantes y del Senado de los Estados Unidos a través de túneles subterráneos.

¿Cómo planea continuar abogando por el SDS y otras enfermedades raras más allá del Día de las Enfermedades Raras?

Planeo seguir siendo un miembro activo de los Defensores Legislativos de Enfermedades Raras este año, defendiendo la legislación para la comunidad de enfermedades raras. Este año planeo ser un Representante Raro de Adultos Jóvenes activa al cumplir 16 años de vida. Planeo seguir utilizando mi experiencia de vivir con un trastorno genético poco común para ampliar aún más el conocimiento de quienes me rodean sobre el SDS y los problemas que rodean a nuestra comunidad. Al utilizar mi historia, puedo tener un respaldo sólido para mis propuestas a los congresistas, brindándoles una conexión personal con la legislación. También planeo seguir publicando en mi cuenta de Instagram de SDS @cure.sds, para brindar información sobre la enfermedad y cómo es la vida diaria.

¿Qué consejo le daría a otras personas interesadas en participar en esfuerzos de defensa de las enfermedades raras?

El consejo que doy a los demás es siempre que utilicen sus experiencias y traumas pasados ​​a su favor en el campo de la defensa. Utilice su visión y conocimiento sobre cómo vivir con alguien con una enfermedad rara o cuidar de ella para poder hablar en contra de los problemas de la comunidad de enfermedades raras. Siempre les digo a las personas que no deben temer a su enfermedad y, en cambio, hacerla parte de ellos. En el trabajo de promoción, es clave aceptar su trastorno para poder verdaderamente hablar y defender lo que es correcto. Al utilizar su historia, puede captar la atención de personas que tal vez nunca hayan oído hablar de su trastorno y estén dispuestas a ayudar. Si recién está ingresando al espacio de la defensa, le recomiendo comenzar poco a poco, creando una plataforma de redes sociales para crear conciencia y brindar información sobre los problemas comunes y la vida diaria de vivir con una enfermedad rara. Nunca te detengas porque algo sale mal, utiliza ese evento negativo como inspiración adicional para seguir prosperando como defensor y como ser humano. No todo va a salir como quieres todo el tiempo, habrá algunos obstáculos en el camino, así que convierte esa negatividad en fuerza.

En nombre de nuestro equipo en SDS Alliance - Joyce, le agradecemos su arduo trabajo, dedicación y defensa apasionada de la comunidad SDS en el Día de las Enfermedades Raras y todos los días. Estamos agradecidos de tenerla como miembro de nuestra comunidad y estamos ansiosos por ver cómo transforma las vidas de tantas personas que viven con una enfermedad rara.

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¡Mira nuestras nuevas infografías sobre SDS (disponibles en inglés y español)!

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Paula shared their story beautifully in a detailed blog on the "Extra Lucky Moms" blog. Check it out!

Below, with Paula's permission, we are sharing some short excerpts.

"When Alex was five months old, he caught a cold. I watched as his little chest keep rising and falling. Then I could see his ribs and collar bone as he tried to suck in air. Something was wrong. His breathing was extremely labored. I rushed him to the emergency room. They immediately took him to a triage room. While they were examining him, I watched as my baby stopped breathing completely. It felt like time stopped, and it may have only lasted about 20 seconds in reality, but it was enough time for his entire body to turn this awful dark purple color. From head to toe, he was the color of an eggplant. I remember looking at the nurse and finally saying “Do something, he’s not breathing!”

"After Alex’s ankle surgery [for a serious infection], one of the doctors recommended we see a genetic specialist. She was the first doctor to look at his entire medical history and suggest that there might be something that ties all of his seemingly random medical events together. So, we made an appointment with another specialist and more tests were done. Alex kept getting sick, coming down with colds, having labored breathing, and having to go to the emergency room. We were at the emergency room or at a doctor’s office almost every two to four weeks. We were hoping for some answers. 

While we waited for his genetic test results to come back in, our pediatrician noticed that Alex was flapping his hands a lot at one of his appointments. He would also occasionally walk on his toes. She started to ask me questions about his speech and his vocabulary. I shared this his vocabulary was limited but I attributed that to all the time he has been spending in the hospital. Then she hit me with something I was not expecting. She recommended we see a behavioral pediatrician to have him evaluated for Autism Spectrum Disorder. He did so many things well that once again, I naively believed that this would simply be an evaluation to check this off the list and rule it out. So, another appointment with another specialist was made.

Then came the two weeks in October of 2020 that I will never forget. First, I received the call from the genetics office. They had Alex’s test results in and confirmed that he had a very rare genetic disorder called Shwachman Diamond Syndrome. All the person from the genetics office could tell me about it was that it is a bone marrow disorder and that I needed to make a follow up appointment with the hematology and oncology team at the children’s hospital. I had so many questions but she could not answer any of them because it was not her specialty. Her job on that call was just to deliver the diagnosis, not provide any answers. So like anyone would do, I went to the internet. And this is when my heart broke again. Shwachman Diamond Syndrome is a bone marrow disease that impacts every single system of the body."

Read the full story on the "Extra Lucky Moms" blog, here.