Rare Endocrinology News

Disease Profile

Shwachman-Diamond syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

Antenatal

ICD-10

D61.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

SDS; Pancreatic insufficiency and bone marrow dysfunction; Shwachman-Bodian syndrome;

Categories

Blood Diseases; Congenital and Genetic Diseases; Digestive Diseases;

Summary

Shwachman-Diamond syndrome (SDS) affects many parts of the body, particularly the bone marrow, pancreas, and skeletal system. Symptoms include the inability to digest food due to missing digestive enzymes, low muscle tone, and anemia. Other symptoms include skeletal findings and intellectual disability. Children with SDS may have feeding difficulties, slow growth, and frequent infections. People with SDS are at increased risk for blood cancers. Shwachman-Diamond syndrome can be caused by the SBDS, DNAJC21, EFL1, or SRP54 gene not working correctly. It can be inherited in either an autosomal recessive or autosomal dominant pattern. SDS is diagnosed is based on symptoms, blood tests, and genetic testing. Treatment may include enzyme and vitamin supplements, blood transfusiongranulocyte-colony stimulating factor (G-CSF), and hematopoietic stem cell transplantation.[1][2][3]

Symptoms

The following list includes the most common signs and symptoms in people with Shwachman-Diamond syndrome (SDS). These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition. 

Signs and symptoms may include:[1][3]

  • Inability to digest food due to lack of digestive enzymes
  • Anemia
  • Low white blood cells (neutropenia)
  • Low platelets (thrombocytopenia)
  • Frequent infections
  • Short stature
  • Rib and/or spine abnormalities
  • Intellectual disability

Babies with SDS have poor feeding, slow growth, and frequent infections. These may get better with age. Many people with SDS have developmental and intellectual delay. Because of bone marrow that doesn't work correctly, people with SDS may be at increased risk for certain blood disorders and cancer.[1][4]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Exocrine pancreatic insufficiency
Inability to properly digest food due to lack of pancreatic digestive enzymes
0001738
30%-79% of people have these symptoms
Chronic neutropenia
0410252
Delayed skeletal maturation
Delayed bone maturation
Delayed skeletal development

[ more ]

0002750
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Hypoamylasemia
0410289
Impaired neutrophil chemotaxis
0040238
Increased mean corpuscular volume
0005518
Increased serum bile acid concentration
0012202
Low levels of vitamin A
Vitamin A deficiency
0004905
Low levels of vitamin D
Deficient in vitamin D
Vitamin D deficiency

[ more ]

0100512
Low levels of vitamin E
Vitamin E deficiency
0100513
Low levels of vitamin K
0011892
Macrocytic anemia
0001972
Malnutrition
0004395
Myelodysplasia
0002863
Normocytic anemia
0001897
Pancreatic hypoplasia
Underdeveloped pancreas
0002594
Short stature
Decreased body height
Small stature

[ more ]

0004322
Steatorrhea
Fat in feces
0002570
Thrombocytopenia
Low platelet count
0001873
Transient neutropenia
0410255
5%-29% of people have these symptoms
Abnormal heart morphology
Abnormality of the heart
Abnormally shaped heart
Heart defect

[ more ]

0001627
Abnormal joint morphology
Abnormal shape of joints
Abnormality of the joints
Anomaly of the joints

[ more ]

0001367
Abnormality of the thoracic cavity
0045027
Acute myeloid leukemia
0004808
Aplastic anemia
0001915
Autistic behavior
0000729
Bone marrow hypocellularity
Bone marrow failure
0005528
Carious teeth
Dental cavities
Tooth cavities
Tooth decay

[ more ]

0000670
Deformed rib cage
0000886
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Leukopenia
Decreased blood leukocyte number
Low white blood cell count

[ more ]

0001882
Metaphyseal chondrodysplasia
0005871
Metaphyseal irregularity
Irregular wide portion of a long bone
0003025
Metaphyseal widening
Broad wide portion of long bone
0003016
Osteopenia
0000938
Pneumonia
0002090
Recurrent bacterial infections
Bacterial infections, recurrent
Frequent bacterial infections
Increased susceptibility to bacterial infections
Recurrent major bacterial infections

[ more ]

0002718
Recurrent viral infections
0004429
Short attention span
Poor attention span
Problem paying attention

[ more ]

0000736
Sinusitis
Sinus inflammation
0000246
Skin rash
0000988
Vertebral compression fractures
Compression fracture
0002953
1%-4% of people have these symptoms
Abnormality of finger
Abnormalities of the fingers
0001167
Abnormality of the outer ear
Abnormality of the external ear
Ear anomalies
External ear malformations
Outer ear abnormality

[ more ]

0000356
Anterior rib cupping
0000907
Delayed eruption of teeth
Delayed eruption
Delayed teeth eruption
Delayed tooth eruption
Eruption, delayed
Late eruption of teeth
Late tooth eruption

[ more ]

0000684
Diabetes mellitus
0000819
Eczema
0000964
Elevated hepatic transaminase
High liver enzymes
0002910
Growth hormone deficiency
0000824
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Hepatomegaly
Enlarged liver
0002240
Ichthyosis
0008064
Immunodeficiency
Decreased immune function
0002721
Oral ulcer
Mouth ulcer
0000155
Osteomyelitis
Bone infection
0002754
Proximal femoral epiphysiolysis
Slipped end

Cause

Shwachman-Diamond syndrome (SDS) is caused by the SBDSDNAJC21, EFL1 or SRP54 gene not working correctly. DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.[1][2]

In about 10% of people, the exact genetic cause has not been found.[1]

Diagnosis

The diagnosis of Shwachman-Diamond syndrome is based on a clinical exam and other diagnostic tests. Blood tests to look at the white blood cells, red blood cells, and platelets may be helpful. Other tests may be done to check for the function of the pancreas, liver, and kidneys. Genetic testing may be used to confirm the diagnosis.[1][3]

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    Treatment for Shwachman-Diamond syndrome (SDS) is based on managing the symptoms. Treatment options include replacement of missing pancreatic enzymes to aid digestion and a special diet that includes fat-soluble vitamins. Additional treatments include blood transfusions and antibiotics. In cases with severe blood disease, a hematopoietic stem cell transplant may be an option.[1][3][4]

    Specialists involved in the care of someone with Shwachman-Diamond syndrome may include:

    • Hematologist
    • Gastroenterologist
    • Medical geneticist
    • Orthopedist
    • Endocrinologist
    • Immunologist

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • Genetics Home Reference (GHR) contains information on Shwachman-Diamond syndrome. This website is maintained by the National Library of Medicine.
      • The National Cancer Institute provides the most current information on cancer for patients, health professionals, and the general public.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Shwachman-Diamond syndrome. Click on the link to view a sample search on this topic.

          References

          1. Nelson A, Myers K. Shwachman-Diamond Syndrome. GeneReviews. Updated Oct. 18, 2018; https://www.ncbi.nlm.nih.gov/books/NBK1756/.
          2. Bezzerri V, Cipolli M. Shwachman-Diamond syndrome: Molecular mechanisms and current perspectives. Mol Diagn Ther. Apr 2019; 23(2):281-290. https://pubmed.ncbi.nlm.nih.gov/30413969.
          3. Nelson AS, Myers KC. Diagnosis, Treatment, and Molecular Pathology of Shwachman-Diamond syndrome. Hematol Oncol Clin North Am. 2018; 32(4):687-700. https://pubmed.ncbi.nlm.nih.gov/30047420.
          4. Farooqui SM, Aziz M. Shwachman-Diamond Syndrome. StatPearls [Internet] Treasure Island (FL): StatPearls Publishing. 2020; https://pubmed.ncbi.nlm.nih.gov/29939643.
          5. Black V. Shwachman Syndrome. National Organization of Rare Disorders (NORD). 2012; https://rarediseases.org/rare-diseases/shwachman-diamond-syndrome/.

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