Expanding the Clinical Features of Schimke Immuno-Osseous Dysplasia: A New Patient with a Novel Variant and Novel Clinical Findings

• Published in: Journal of clinical research in pediatric endocrinology
• Main Authors: Alavanda, Ceren, Demir, Şenol, Güven, Serçin, Eltan, Mehmet, Bilgiç Eltan, Sevgi, Sefer, Asena Pınar, Pul, Serim, Güran, Tülay, Alpay, Harika, Arman, Ahmet, Ata, Pınar, Turan, Serap
• Format: Journal Article
• Language: English
• Published: Turkey 08-08-2024
• Subjects: hypercalcemia; SMARCAL1; ectopic kidney; hypophosphatemia; gonadal dysfunction
• ISSN: 1308-5727; 1308-5735; 1308-5735
• DOI: 10.4274/jcrpe.galenos.2024.2024-1-17

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 and spondyloepiphyseal dysplasia and facial dysmorphism. Biallelic variants in the
gene cause SIOD. The five-and-half-year-old female patient was evaluated because of short stature, dysmorphism, hypercalcemia, hypophosphatemia and elevated FSH levels. Karyotype analysis and array-CGH testing were normal. Clinical Exome Sequencing was performed via next-generation sequencing to analyze genes associated with hypophosphatemia. No pathogenic variant was detected. The subsequent detection of proteinuria during her follow-up for cross-fused ectopic left kidney ultimately facilitated the diagnosis of SIOD, although no obvious spondyloepiphyseal dysplasia was detected. Re-analysis of CES revealed a novel homozygous c.2422_2427+9delinsA pathogenic variant in the
. One hundred twenty-five SIOD cases from 38 literature reporting
gene pathogenic variants were 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 time these findings had been reported in a SIOD patient. This report expands not only the phenotypic but also genotypic spectrum of SIOD.