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Sensibiliser

Souhaitez-vous contribuer à la sensibilisation et au financement du syndrome de Shwachman-Diamond ? Vous êtes au bon endroit! Vous trouverez de nombreux outils ici, et nous continuerons à en ajouter d'autres. N'hésitez pas à demander tout ce dont vous pourriez avoir besoin.

La sensibilisation aide à sauver des vies.

  • La sensibilisation du grand public augmente les chances que les familles des patients envisagent de poursuivre un diagnostic plus tôt et bénéficient ainsi de meilleurs soins médicaux

  • La sensibilisation de la communauté médicale aide les prestataires à envisager un diagnostic de SDS plus tôt et leur permet de fournir de meilleurs soins médicaux

  • La sensibilisation de la communauté de la recherche peut attirer plus de projets de recherche et de collaborations, accélérant ainsi le développement de traitements

La collecte de fonds aide à soutenir nos programmes essentiels nécessaires pour permettre et accélérer la recherche.

Why is early diagnosis of SDS critical?

 

Early diagnosis is essential to enable access to appropriate clinical care, access to research opportunities, and connections to community support. In particular, appropriate surveillance to enable early intervention that may reduce the risk of potentially life-threatening complications, including:

Cancer

An estimated 30% of patients develop MDS or AML by age 30. [1,2] 

Sepsis

Most patients are neutopenic and require a fever protocol. [3,4]

FTT

Many patients fail to thrive (FTT) due to EPI, which is treatable by PERT. [3,4]

Who should be tested?

 

The symptoms of Shwachman-Diamond Syndrome are variable, both in terms of symptom onset, and severity [5,6]. It is easy to miss, with dangerous consequences. Current clinical diagnostic guidelines suggest that patients with a clinical suspicion for Shwachman-Diamond Syndrome should receive genetic testing if they have a history of two or more of the following symptoms:

  • 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

A "history of" means that these symptoms may have happened in the past and resolved by the time testing is considered. Patients should still be tested for SDS even if symptoms have already resolved, or were very mild.

 

​All patients who present with myelodysplastic syndrome (MDS) or Acute Myeloid Leukemia (AML) - regardless of age, but especially those under the age of 50 - need to get tested for genetic germline heme malignancy disorders, including SDS and other leukemia predisposition and bone marrow failure disorders [7-10]. This is critical for enabling the care team to select the best course of treatment, as SDS patients will require specialized protocols and regimens. We cannot overstate the vital importance of this, as a matter of life and death. We also recognize that covering the cost of germline testing through health insurance may be challenging, especially in the adult population. If you have difficulties getting coverage, please consider the resources below. If you are a healthcare provider, please reach out to an SDS expert in your area. We can help you get connected. Email us at connect@sdsalliance.org.

How is SDS diagnosed?

 

The most accurate and fastest way to diagnose SDS is through genetic testing. Over 90% of patients have mutations in a gene called SBDS. Both this gene and a few others that are associated with SDS can be tested through sequencing. Currently, most clinical genetic testing relies on Next Generation Sequencing (NGS) or Whole Exome Sequencing, and the analysis of the results typically focuses on certain groups of genetic disorders (often referred to as a target panel). Many - but not all - genetic testing companies cover the SBDS and the other genes of interest. Make sure that the test you receive covers the SBDS gene. All the resources we share below cover our genes of interest appropriately. (Note: NONE of the INVITAE panels or tests cover the SBDS gene. Do not rule out SDS based on testing through INVITE!).

If the genetic testing results are inconclusive, a clinical diagnosis can be considered. This relies on experienced physicians to diagnose the relevant set of symptoms. We are happy to help you connect with a clinical expert in your area. Email us at connect@sdsalliance.org. ​A clinical diagnosis should not replace efforts toward a genetic diagnosis.

View this video in Spanish

Inconclusive results?

If your results were inconclusive (i.e., one or more variants of uncertain significance were identified), we encourage you to periodically check in with the care team member who originally ordered genetic testing to see if there have been any changes in the classification of the variant(s) identified. As our scientific understanding of SDS expands, sometimes variants of uncertain significance (VUS) can be upgraded to positive (i.e., pathogenic or likely pathogenic) or downgraded to negative (i.e., benign or likely benign). Changes in the classification of these VUSs can have implications for care management, surveillance, and potentially genetic testing for other family members. Further genetic work-up for individuals with a clinical concern for SDS may be helpful for those with negative genetic testing – approximately 10% of individuals with a clinical concern for SDS do not have a known genetic cause, suggesting that pathogenic variant(s) may be in other genes not yet identified. For those with previous negative or inconclusive genetic testing, there are other more thorough types of genetic testing, such as whole exome sequencing (WES) or whole genome sequencing (WGS), that look for errors in the entire instruction manual, meaning all of the genes in your cells (over 20,000!) are analyzed. These kinds 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. If only one pathogenic variant was identified in an autosomal recessive SDS gene (e.g., SBDS, EFL1, or DNAJC21), OR one or more variants of uncertain significance were identified, OR genetic testing results were negative, you may be eligible to participate in one or more of these research genetic testing opportunities. It is important to note that participating in research-based genetic testing may take longer than clinical genetic testing and that not all individuals who participate will have a result identified. If one or more variants are identified in the research setting, these findings may need to be confirmed with clinical genetic testing before they can be used to help guide medical management.

Should I get genetic testing even if I already have a clinical SDS diagnosis?

 

Absolutely yes!

  • As highlighted above, an early and accurate diagnosis is critical for your healthcare team to partner with you to find the best treatment options.

  • New therapies in various stages of development (including clinical trials) are often designed to target patients with specific gene variants. Eligibility for many clinical trials requires that patients know what gene variants they have, which relies on appropriate genetic testing.

  • Knowing your genetic variant can help explore family planning options, including IVF. A genetic counselor can help you learn about these options.

The National Organization for Rare Disorders (NORD) has published new animated videos and flyers in English and Spanish about why rare disease patients should get genetic testing if they already have a diagnosis. 

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View this video in Spanish

Do you want to learn more about SDS genetics and testing strategies?

 

Check out these video resources

Dépliants et brochures

Envoyez-nous un e-mail à connect@SDSAlliance.org si vous avez besoin de copies papier.

United States
Probably Genetic

For patients who have not had genetic testing before, we have partnered with Probably Genetic to provide free, whole exome sequencing (WES) based, clinical-grade genetic testing. Learn more.

US residents (except NY) only.

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NICER Comprehensive Immune and Cytopenia (CIC) Panel

Eligibility: Patients must be referred by a NICER Institutional Member in order to qualify for this sponsored testing. The target population is patients with hematologic and/or immunologic presentations, but without a definitive diagnosis, in which genetic testing will aid in diagnosis. Patients must also consent to the NICER patient registry to be eligible for testing, in which de-identified clinical and laboratory data will be stored for future research in the NICER community. Patient registry and sponsored testing programs will be regulated through a central Institutional Review Board (IRB) at the University of Michigan.

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Rare Genomes Project

A free and remote research program using genomic sequencing (WGS) 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, they will work with your doctor to confirm the result. Learn more.

US residents only.

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Project FIND-OUT

A research project to help parents get answers about potential genetic causes of their child’s symptoms, only open to infants in the United States between the ages of 3-12 months. Project FIND-OUT provides free genetic counseling and testing to eligible individuals who have 2 or more of the below symptoms:

  • Feeding issues
  • Issues with movement

  • NICU admission

  • Developmental delays

  • Other (congenital malformations, atypical growth or specialist referral)

  • Unprovoked seizures

  • Tone

US residents only, infants age 3-12 months only.

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Undiagnosed Disease Network (UDN)

The UDN is a research study that is funded by the National Institutes of Health. Its purpose is to bring together clinical and research experts from across the United States to solve the most challenging medical mysteries using advanced technologies. Through this study, the UDN hopes to both help individual patients and families living with the burden of undiagnosed diseases, and contribute to the understanding of how the human body works. The Clinical Sites, where UDN participants are evaluated, are located in 14 cities across the United States as outlined on their website. In addition to answering several questions regarding demographics, medical history, and prior evaluations, the application to the UDN also requires a study recommendation letter from a health care provider (for example, specialist, primary care physician, nurse practitioner, or genetic counselor). If accepted to the UDN, participating providers will determine which further evaluations (including genetic testing options) may be required to help determine a diagnosis

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Europe, Australia, and other Countries/Regions


Check out the registries below and contact them for assistance. The SCNIR-Europe branch, based in and listed under Germany, may be able to assist with testing for patients worldwide. The Italian registry has also been very accommodating to international patients from across Europe. We are very grateful for these wonderful programs for helping SDS patients in need. Click on the image below to navigate to the relevant resource page.

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​References

  1. Reilly CR, Shimamura A. Predisposition to myeloid malignancies in Shwachman-Diamond syndrome: biological insights and clinical advances. Blood. 2023;141(13):1513-1523. doi:10.1182/blood.2022017739

  2. Alter BP, Giri N, Savage SA, Rosenberg PS. Cancer in the National Cancer Institute inherited bone marrow failure syndrome cohort after fifteen years of follow-up. Haematologica. 2018;103(1):30-39. doi:10.3324/haematol.2017.178111

  3. Dror Y, Donadieu J, Koglmeier J, et al. Draft consensus guidelines for diagnosis and treatment of Shwachman‐Diamond syndrome. Ann N Y Acad Sci. 2011;1242(1):40-55. doi:10.1111/j.1749-6632.2011.06349.x

  4. Nelson A, Myers K. Shwachman-Diamond Syndrome Synonym: Shwachman-Bodian-Diamond Syndrome Summary Clinical characteristics. https://www.ncbi.nlm.nih.gov/books/NBK1756/

  5. Myers KC, Bolyard AA, Otto B, et al. Variable clinical presentation of Shwachman-Diamond syndrome: update from the North American Shwachman-Diamond Syndrome Registry. J Pediatr. 2014;164(4):866-870. doi:10.1016/j.jpeds.2013.11.039

  6. Thompson AS, Giri N, Gianferante DM, et al. Shwachman Diamond syndrome: narrow genotypic spectrum and variable clinical features. Pediatr Res. 2022;92(6):1671-1680. doi:10.1038/S41390-022-02009-8

  7. Lucy A. Godley et al., Germline Predisposition in Hematologic Malignancies: Testing, Management, and Implications. Am Soc Clin Oncol Educ Book 44, e432218(2024). DOI:10.1200/EDBK_432218

  8. Lindsley RC, et al.,. Prognostic Mutations in Myelodysplastic Syndrome after Stem-Cell Transplantation. N Engl J Med. 2017 Feb 9;376(6):536-547. doi: 10.1056/NEJMoa1611604.

  9. Feurstein, Simone et al. “Germ line predisposition variants occur in myelodysplastic syndrome patients of all ages.” Blood vol. 140,24 (2022): 2533-2548. doi:10.1182/blood.2022015790

  10. Feurstein, Simone et al. “Germline variants drive myelodysplastic syndrome in young adults.” Leukemia vol. 35,8 (2021): 2439-2444. doi:10.1038/s41375-021-01137-0

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