J Clin Res Pediatr Endocrinol. Ahead of Print: JCRPE-47113 | DOI: 10.4274/jcrpe.galenos.2024.2024-1-17

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

Ceren Alavanda¹, Þenol Demir², Serçin Güven³, Mehmet Eltan⁴, Sevgi Bilgiç Eltan⁵, Asena Pýnar Sefer⁵, Serim Pul³, Tülay Güran⁴, Harika Alpay³, Ahmet Arman², Pýnar Ata², Serap Turan^4
1Department of Medical Genetics, Van Research and Training Hospital, Van, Türkiye
²Department of Medical Genetics, School of Medicine, Marmara University, Istanbul, Türkiye
³Department of Pediatric Nephrology, School of Medicine, Marmara University, Istanbul, Türkiye
⁴Department of Pediatric Endocrinology, School of Medicine, Marmara University, Istanbul, Türkiye
⁵Department of Pediatric Allergy and Immunology, School of Medicine, Marmara University, Istanbul, Türkiye

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 SMARCAL1 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 SMARCAL1. One hundred twenty-five SIOD cases from 38 literature reporting SMARCAL1 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.

Keywords: SMARCAL1, hypercalcemia, hypophosphatemia, ectopic kidney, gonadal dysfunction

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