"We have reached the stage of acceptance and trying to live life the fullest despite SDS" Shares Octavian's dad, Raul. Read this Romanian family's story, here. 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. A holistic approach of his condition was undertaken in Verona and after careful evaluation, Octavian was confirmed clinically with SDS .  [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. We came back to Romania with a plan and clear indications on how to administer enzymes to help him digest food and we have scheduled a follow up visit in the coming year. 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. Despite his condition he is a very happy little man. He smiles all the time, he is very happy to spend time with his older brother and is musically inclined – his face lights up when we put music on.  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. We went from being completely lost, to having a plan, and for the first time in our SDS journey I think we have reached as a family the stage of acceptance and trying to live life the fullest despite SDS. [Written and submitted from Octavian's dad, Raul]

In this issue: How do lung microbiomes improve outcomes for bone marrow transplant patients? 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. Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

In this issue: What is the difference between germline and somatic genetic testing? 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. Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

In this issue: Is a new screening test for SDS on the horizon? 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. Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

In this issue: SDS identified as a common cause of inherited neutropenia in the Israeli Inherited Bone Marrow Failure Registry! 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. Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

In this issue: A new publication describing the symptoms of SDS in patients in China! 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. Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

In this issue: New study publishes growth charts custom for individuals with SDS! 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. Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

In this issue: New research opportunity for siblings to individuals with SDS! 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:

In this issue: What are experts saying about the importance of genetic testing in individuals with bone marrow failure? 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? 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. 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. Uncovering a genetic cause for the person with bone marrow failure can lead to changes in treatment planning and screening recommendations moving forward. Genetic testing results may also change who is chosen as a donor if the person plans to have a bone marrow transplant. 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:

In this issue: How are advances in genetic testing technology changing newborn screening and the course of the diagnostic odyssey in rare disease? 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. Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post:

In this issue: Three different case reports about various aspects of SDS, and the affected SDS patients' unique experiences. 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: "Ultrastructural analysis of SDS-related hepatic pathology has not been previously reported. In our patient, EM on liver biopsy specimens was notable for numerous small mitochondria that were densely packed within the cytoplasm, reminiscent of “oncocytic transformation” usually seen with the primary mitochondrial condition, mitochondrial DNA depletion syndrome." 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: "SDS-related liver disease has an overall good prognosis, as the elevates transaminases, hepatosteatosis, and fibrosis tend to normalize around 5 years of age. Adult patients with SDS usually have no evidence of clinical liver disease, with few rare exceptions." 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: "Interestingly, the SBDS gene variants that were ultimately identified on the patients WGS were within genetic regions that could have been identified on WES, with one variant within exon 2 (c.183_184delTAinsCT), and the other a 5′ donor splice-site mutation between exons 2 and 3 (c.258 + 2T > C). This is significant because c.183_184delTAinsCT and c.258 + 2T > C are two of the most common pathogenic variants in SBDS." 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 present, pre-transplant bridging therapy has emerged as one of the important options with improved efficacy, reduced tumor burden, and less treatment-related toxicity. Here we reported azacitidine combined with venetoclax was used as pre-transplant bridging regimen in a TP53-mutant AML-MR case developed from SDS. He achieved complete remission with incomplete recovery and proceeded to Allo-HSCT. We hope to provide some evidence and insight for in-depth research and clinical treatment by presenting this case." 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. "She reported exposure to pet rats, dogs, cats, chickens, guinea pigs, sugar gliders, and a snake." 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:

In this issue: Why is genetic testing for SDS important and how do I access it? 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! __________________________________________________________________________________ Do you enjoy the SDS & Science Snapshots? You can Sign up by using the button on the top right of this post: