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
- Cystic fibrosis
- Johanson-Blizzard syndrome
- Pearson’s syndrome
- SPINK1-related severe infantile isolated exocrine pancreatic insufficiency
- Diamond-Blackfan anaemia
- Fanconi anaemia
- Dyskeratosis congenita
- Kostmann’s syndrome
- ELANE-related neutropenia
- Cartilage-hair hypoplasia
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
Patients with Shwachman-Diamond syndrome should be referred to a centre where they can receive appropriate haemato-oncological care and genetic counselling.
Early detection measures should include
- Regular clinical examinations
- CBC including reticulocytes every 3-4 months
- Bone marrow aspiration and biopsy and somatic gene panel annually
- Patients with SDS, their families, and their physicians should be aware of suspicious clinical symptoms that may indicate the development of leukaemia
- Familiy history should be regularly updated for neoplasia, cytopenias and haemorrhages
