Shwachman – Diamond Syndrome: Modern Genetic Aspects of a Ribosomapathy

For citation: Ipatova M.G. Shwachman — Diamond Syndrome: Modern Genetic Aspects of a Ribosomapathy. Doctor.Ru. 2020; 19(10): 33–36. (in Russian). DOI: 10.31550/1727-2378-2020-19-10-33-36
30 november 2020

Objective of the Review: To analyse new DNAJC21, EFL1, SRP54 mutations causing ribosome biogenesis defects and presenting with clinical symptoms similar to the symptoms of Shwachman – Diamond syndrome (SDS).

Key Points. SDS is a ribosomapathy and is characterised by pancreatic exocrine insufficiency, defective hematopoiesis, musculoskeletal anomalies, and a high risk of myelodysplastic syndrome and acute myeloid leukemia. About 90% of SDS patients have biallelic SBDS mutations. However, 10–20% of patients with a set of symptoms typical of SDS did not have any pathovars in SBDS gene; therefore, we searched for other candidate genes. In addition to SDS, genetic disorders associated with defected maturation, deficient structure or function of ribosomes and ribonucleoprotein complexes include Diamond – Blackfan anemia, cartilage and hair hypoplasy (McKusick type metaphyseal chondrodysplasia), congenital diskeratosis, 5q-syndrome, and others. These syndromes are similar to SDS. All these conditions are associated with medullary deficiency at least in one hematopoiesis chain. All five conditions are associated with a high risk of cancer.

Conclusion. SDS is a genetically determined condition belonging to ribosomapathies. Ribosomapathies are caused by mutations in genes that participate in the synthesis of ribosomal proteins and factors, functioning at various stages of their assembly, and give origin to a number of clinical phenotypes, including haematological malignancies and cancer. In clinical practice, SDS is diagnosed on the basis of typical clinical symptoms and if pathogenic SBDS mutations are present. The issue whether SDS is a genetic heterogenetic ribosomapathy or a mutation of other genes causing defective ribosome synthesis and SDS-like symptoms, is disputable and requires further research. 

Conflict of interest: The authors declares that she does not have any conflict of interests.

M.G. Ipatova — N.I. Pirogov Russian National Research Medical University (a Federal Government Autonomous Educational Institution of Higher Education), Russian Federation Ministry of Health; 1 Ostrovityanov St., Moscow, Russian Federation 117997. N.F. Filatov Municipal Clinical Children Hospital of Moscow Department of Health; 15 Sadovaya-Kudrinskaya Str., Moscow, Russian Federation 123001. eLIBRARY.RU SPIN:1837-5380. http://orcid.org/0000-0003-0295-4820. E-mail: mariachka1@mail.ru


Fig. Ribosomal cycle [23]


Received: 25.09.2020

Accepted: 16.10.2020

30 November 18:26
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