Shwachman Diamond Syndrome – Definition
Shwachman Diamond Syndrome (OMIM #260400) is the second most common cause of exocrine pancreatic insufficiency in children after cystic fibrosis. The disease is associated with bone marrow failure and an increased risk of malignant diseases of the hematopoietic system. Clinically, patients often present with skeletal malformations and short stature.
Synonyms:
SDS, Shwachman-Bodian-Diamond syndrome, congenital pancreatic lipomatosis
Gene:
DNAJC21, EFL1, SBDS, SRP54
Gene product:
ATP-dependent DNA helicase DDX11
Function:
Cohesion of sister chromatids and DNA replication, tumor suppressor
Pattern of inheritance:
in most cases autosomal recessive (DNAJC21, EFL1, or SBDS), autosomal dominant (SRP54), de novo
Prevalence:
1: 77.000
Genotype-phenotype correlation:
Unknown
Penetrance:
Unknown
Shwachman Diamond Syndrome – Diagnosis
- Clinical presentation with exocrine pancreal insufficiency and bone marrow failure
and/or - Biallelic variants in the DNAJC21, EFL1, or SBDS gene or heterozygous variant in the SRP54 gene(at least likely pathogenic or pathogenic)
Differential Diagnoses
- Zystische Fibrose
- Johanson-Blizzard Syndrom
- Pearson Syndrom
- SPINK1-related severe infantile isolated exocrine pancreatic insufficiency
- Diamond-Blackfan Anämie
- Fanconi Anämie
- Dyskeratosis congenita
- Kostmann-Syndrom
- ELANE-related neutropenia
- Knorpel-Haar Hypoplasie
Clinical Presentation
Clinical Anomalies
- Exocrine pancreatic insufficiency with reduced pancreatic enzymes, reduced elastase-1 in the stool, deficiency of fat-soluble vitamins
- Neutropenia, anemia, thrombocytopenia up to pancytopenia
- Short stature, skeletal anomalies (e.g., chondrodysplasia, thoracic deformities)
- Hepatomegaly, sometimes with elevated liver values
- Congenital malformations of the heart or ears
Tumor Predisposition
- Malignant diseases of the hematopoietic system (leukemias, bone marrow hypocellularity or failure)
Special Features of Treatment
- The prolonged administration of cytokines or growth factors such as G-CSF must be carefully considered, as transformation into leukemic cells cannot be ruled out
- There is no standard chemotherapeutic treatment regimen for diseases. In the case of leukemia or bone marrow failure, the only curative therapy is stem cell transplantation
Diagnosis of Shwachman Diamond Syndrome- What's Next?
Once diagnosed, it is recommended that a cancer predisposition specialist manage the patient. The following section explains whether cancer screening tests or other measures are necessary and how they should be performed. Some additional information, including links to support groups, is also included at the end of this page.
Diagnosis of Shwachman Diamond Syndrome- What's Next?
Once diagnosed, it is recommended that a cancer predisposition specialist manage the patient. The following section explains whether cancer screening tests or other measures are necessary and how they should be performed. Some additional information, including links to support groups, is also included at the end of this page.
Recommendations for Early Detection in Your Patients
To date, there are no standardized screening recommendations for patients with SDS. Based on the currently available literature, the following is suggested:
- Differential blood count every 3-6 months, shorter interval if necessary in the case of infections or changes in the cell series
- Bone marrow punctures every 1-3 years, shorter intervals if necessary in case of abnormalities
- Checking the nutritional situation every 6 months
- Checking the vitamin balance every 6 months to monitor pancreatic enzyme therapy
- During the fastest growth phases, orthopedic checks and, if necessary, X-ray checks of the knee and hip
- Bone densitometry before, during, and after puberty
- Developmental monitoring up to 6 years of age, then semi-annual checks on length of growth
- Neuropsychological screening at the ages of 6-8, 11-13, and 15-17 years
Shwachman Diamond Syndrome – Further Information
Additional Resources
Unfortunately, we are currently not aware of any support groups for patients with Shwachman Diamond syndrome. New information will be added as soon as it becomes available.
