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SDS & Science Snapshots (2023-12-16)

In this issue: What does it mean to have a clinical diagnosis of SDS and who are some of the important care team members who can help?

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 or message us on Facebook! This is all for you!

The Role of Multidisciplinary Care Teams in Establishing a Clinical Diagnosis of SDS

Over the past few months in our Science Snapshot series, we have discussed the diagnostic odyssey for SDS from multiple perspectives including considerations for receiving a genetic diagnosis of SDS and the cost of a delayed diagnosis. In our Science Snapshot this week, highlighting this article published by researchers at the National Cancer Institute (NCI), we will be reviewing what it means to have a clinical diagnosis of SDS and how a multidisciplinary care team can be critical in making an SDS diagnosis.

We have also touched on this topic last weekend at our "Ask an Expert" community chat, where our guest expert Ashley Thompson, board certified genetic coucelor and new team member at the SDS Alliance, presented on genetic testing and offered her insights. If you missed the live session, you will be able to catch up on the recording on our YouTube channel. (Coming soon. We will update the link below).

What is a Clinical Diagnosis of SDS?

Diagnosing SDS involves a comprehensive assessment of clinical features, genetic testing, and consideration of associated complications. Differentiating between clinical and genetic diagnoses is essential in understanding SDS. A clinical diagnosis relies on the identification of observable symptoms and features through physical examinations and medical history assessments. Clinical diagnosis of SDS are often made based on the presentation of hallmark symptoms of SDS, including exocrine pancreatic insufficiency, neutropenia, and skeletal. In contrast, a genetic diagnosis of SDS involves completing genetic testing to identify genetic mutations in a known SDS gene.

While positive genetic testing can confirm a clinical diagnosis of SDS, it is important to recognize negative genetic testing does not rule-out a clinical diagnosis of SDS. Interestingly, approximately 10% of individuals with SDS actually have negative genetic testing. Research to discover new SDS genes is on-going. Individuals with a clinical suspicion for SDS and negative genetic testing should talk with their care team about what additional testing could be informative.

Does clinical presentation of SDS correlate with genetic status?

In a manuscript that was published last year, researchers at the NCI attempted to determine if there was a difference in clinical presentation of SDS based on an individual’s specific genetic variant (i.e, mutation) by analyzing the medical records of fifty-four participants with a clinical suspicion SDS in their Inherited Bone Marrow Failure Syndromes cohort. In Figure 1 from this article (as shown below), the authors presented the classification schema they used in establishing a clinical diagnosis of SDS versus an SDS-like clinical presentation. Individuals with both pancreatic insufficiency and neutropenia were considered to have a classical presentation of SDS. While the authors determined those with either pancreatic insufficiency or neutropenia in the presence of a hypocellular bone marrow constituted an SDS-like diagnosis.

Contrary to their hypothesis, the findings of this study suggest there was no distinct clinical presentation associated with an individual’s specific genetic change (i.e., mutation). Overall, the authors reported a narrow genotypic spectrum in not only the SDS cohort at the NCI, but also in other cohorts based on a literature review - the c.258+2T>C and c.183_184TA>CT variants in SBDS were the most common genetic changes in those with SDS. The hallmark clinical features of SDS, including exocrine pancreatic insufficiency, neutropenia, and skeletal dysplasia, were observed consistently among patients with positive genetic testing regardless of the variant type (i.e., a common vs more rare variant in SBDS). Additionally, the study noted a higher prevalence of MDS and AML among pediatric SDS patients with an known genetic cause, indicating an increased risk of hematologic malignancies in this population. The rarity of solid malignancies, such as breast and ovarian cancer, was also highlighted.

How a Multidisciplinary Care Team Can Help Establish an SDS Diagnosis

This study emphasizes the need for a collaborative approach involving various specialties to streamline the diagnostic process, provide comprehensive care, and address potential complications, including an increased risk of hematologic malignancies in pediatric SDS patients. We have adapted Figure 4 from this article (see below) to provide a visual of the different providers and evaluations that can play an important role in establishing an SDS diagnosis. This collaborative approach to receiving an SDS diagnosis ensures a comprehensive evaluation of clinical features and facilitates the incorporation of genetic testing for confirmation. Early diagnosis facilitated by a multidisciplinary team can help ensure prompt initiation of appropriate treatment and management strategies for individuals with SDS.


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.

Shwachman Diamond syndrome: narrow genotypic spectrum and variable clinical features.

Thompson AS, Giri N, Gianferante DM, Jones K, Savage SA, Alter BP, McReynolds LJ. Pediatr Res. 2022 Dec;92(6):1671-1680. doi: 10.1038/s41390-022-02009-8. PMID: 35322185

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