Abstract
Schimke immuno-osseous dysplasia (SIOD) (MIM:242900) is an ultra-rare, autosomal recessive, pan-ethnic pleiotropic disease. Typical findings of this syndrome are steroid-resistant nephrotic syndrome, cellular immunodeficiency, spondyloepiphyseal dysplasia (SED) and facial dysmorphism. Biallelic variants in the SMARCAL1 gene cause SIOD. The five-and-a-half-year-old female patient was evaluated because of short stature, dysmorphism, hypercalcemia, hypophosphatemia, and elevated follicle-stimulating hormone (FSH) levels. Karyotype analysis and array-CGH testing were normal. Clinical exome sequencing (CES) was performed to analyze genes associated with hypophosphatemia. No pathogenic variant was detected. The subsequent detection of proteinuria during follow-up for cross-fused ectopic left kidney ultimately facilitated the diagnosis of SIOD, although no obvious SED was detected. Re-analysis of CES revealed a novel homozygous c.2422_2427+9delinsA pathogenic variant in the SMARCAL1. The literature on SMARCAL1 gene pathogenic variants, including 125 SIOD cases from 38 articles was reviewed to investigate whether hypercalcemia, hypophosphatemia, and elevated FSH levels had been previously reported in SIOD patients. This review revealed that this was the first report of these findings in a patient with SIOD. Thus, this report expands both the phenotypic and genotypic spectrum of SIOD.
Keywords: SMARCAL1, hypercalcemia, hypophosphatemia, ectopic kidney, gonadal dysfunction
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