» Articles » PMID: 40004207

Genetic and Clinical Features of Schimke Immuno-Osseous Dysplasia: Single-Centre Retrospective Study of 21 Unrelated Paediatric Patients over a Period of 20 Years

Abstract

Schimke immuno-osseous dysplasia (SIOD) is a hereditary autosomal-recessive multi-system disorder with early mortality. It has variable clinical presentations, mainly characterised by disproportional short stature, steroid-resistant nephrotic syndrome, spondyloepiphyseal dysplasia, and T-cell immunodeficiency. In the majority of cases, SIOD is caused by pathogenic sequence variants (PSVs) in the gene that encodes protein involved in chromatin remodelling. SIOD is an ultra-rare condition, with an incidence of ~1 per 1-3 million live births; data on its genetic and clinical features are scarce. We conducted a retrospective study of 21 paediatric patients with SIOD diagnosed in our centre during the years 2003-2023. The most common extra-renal clinical features were short stature, osseous dysplasia, multiple stigmas, and leukopenia. Proteinuria of varying severity was observed in 16 cases. The five-year overall survival rate (OS) was 89% (95% CI 77-100%), and the ten-year OS was 10%. Next-generation sequencing (NGS) revealed the following PSVs in in 19 patients: , , , , , , , , , , , , , and ; the most common was , resulting in premature translation termination (p.E848*), and it was found in 14 patients either in a homozygous (four patients) or compound-heterozygous (10 patients) state. According to microsatellite analysis, it is a "founder mutation" in Russia.

References
1.
Horton A, Lunke S, Sadedin S, Fennell A, Stark Z . Elusive variants in autosomal recessive disease: how can we improve timely diagnosis?. Eur J Hum Genet. 2023; 31(4):371-374. PMC: 10133393. DOI: 10.1038/s41431-023-01293-0. View

2.
Santangelo L, Gigante M, Netti G, Diella S, Puteo F, Carbone V . A novel SMARCAL1 mutation associated with a mild phenotype of Schimke immuno-osseous dysplasia (SIOD). BMC Nephrol. 2014; 15:41. PMC: 3973878. DOI: 10.1186/1471-2369-15-41. View

3.
Nayak M, Mishra B, Gaikwad S, Sarma K, Tripathi M . Moyamoya Syndrome in Schimke Immune-Osseous Dysplasia: A Rare Association. Cureus. 2022; 14(6):e25838. PMC: 9273200. DOI: 10.7759/cureus.25838. View

4.
Sarin S, Javidan A, Boivin F, Alexopoulou I, Lukic D, Svajger B . Insights into the renal pathogenesis in Schimke immuno-osseous dysplasia: A renal histological characterization and expression analysis. J Histochem Cytochem. 2014; 63(1):32-44. PMC: 4395996. DOI: 10.1369/0022155414558335. View

5.
Bertaina A, Grimm P, Weinberg K, Parkman R, Kristovich K, Barbarito G . Sequential Stem Cell-Kidney Transplantation in Schimke Immuno-osseous Dysplasia. N Engl J Med. 2022; 386(24):2295-2302. PMC: 10545450. DOI: 10.1056/NEJMoa2117028. View