Abstract:

Objective To summarize the clinical characteristics of five children with Schimke immunoosseous dysplasia (SIOD) and analyze the variants in the SMARCAL1 gene, aiming to enhance the understanding of SIOD and underscore the significance of genetic diagnosis. Methods Clinical data and genetic testing results were retrospectively collected from five SIOD patients who presented to the Nephrology Department between 2016 and 2024. Results Patients 1, 2, and 3 died after 1 year, 1 year and 3 months, and 8 months of follow-up, respectively. Patient 4 exhibited progressive proteinuria during 9 months of follow-up but maintained normal renal function. Patient 5 was followed for 9 years; bilateral hip dislocation occurred at the age of 18, for which hip replacement surgery was performed. At 19 years of age, he presented with short stature, stable urinary protein levels, and preserved renal function. All patients underwent sequencing of the SMARCAL1 gene. No pathogenic variant was identified in patient 1. Patient 2 was compound heterozygous for the splice variants c.1334+1G>A and c.1335-2A>C. Patient 3 was homozygous for the missense variant c.2425G>A (p.G809R). Patient 4 was homozygous for the frameshift variant c.1071delT (p.F357LfsTer26). Patient 5 was compound heterozygous for the variants c.445C>T (p.Q149X) and c.1933C>T (p.R645C). Among these, c.1334+1G>A, c.2425G>A, c.445C>T, and c.1933C>T are known pathogenic or likely pathogenic variants, while c.1335-2A>C and c.1071delT represent novel variants not previously reported in the literature. Conclusions SIOD presents with characteristic multisystem clinical features, yet exhibits marked phenotypic variability. The genotype-phenotype correlation remains poorly defined. Early diagnosis enables avoidance of unnecessary immunosuppressive therapies, including corticosteroids, and supports timely symptomatic management. Despite advances in supportive care, the overall prognosis remains poor.

Key words: Schimke immunoosseous dysplasia, variation, SMARCAL1, child