BACKGROUND: Schimke immunoosseous dysplasia (SIOD) is an ultra-rare inherited disease affecting many organ systems. Spondyloepiphyseal dysplasia, T-cell immunodeficiency and steroid resistant nephrotic syndrome are the main symptoms of this disease. CASE PRESENTATION: We aimed to characterize the clinical, pathological and genetic features of SIOD patients received at tertiary Pediatric Nephrology Center, University Hospital Motol, Prague, Czech Republic during the period 2001-2021. The mean age at diagnosis was 21 months (range 18-48 months). All patients presented with growth failure, nephropathy and immunodeficiency. Infections and neurologic complications were present in most of the affected children during the course of the disease. CONCLUSIONS: Although SIOD is a disease characterized by specific features, the individual phenotype may differ. Neurologic signs can severely affect the quality of life; the view on the management of SIOD is not uniform. Currently, new therapeutic methods are required.

• Keywords
• Case series, Chronic kidney disease, Nephropathy, Schimke immunoosseous dysplasia, Transient ischemic attacks, Transplantation,
• MeSH
• Arteriosclerosis MeSH
• Tertiary Care Centers MeSH
• Quality of Life MeSH
• Humans MeSH
• Nephrotic Syndrome * diagnosis   genetics   complications   MeSH
• Osteochondrodysplasias * diagnosis   genetics   therapy   MeSH
• Pulmonary Embolism MeSH
• Primary Immunodeficiency Diseases MeSH
• Immunologic Deficiency Syndromes * diagnosis   genetics   complications   MeSH
• Rare Diseases MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Case Reports MeSH
• Geographicals
• Czech Republic MeSH

Schimke immuno-osseous dysplasia (SIOD) is a rare multisystem disorder with early mortality and steroid-resistant nephrotic syndrome (SRNS) progressing to end-stage kidney disease. We hypothesized that next-generation gene panel sequencing may unsurface oligosymptomatic cases of SIOD with potentially milder disease courses. We analyzed the renal and extrarenal phenotypic spectrum and genotype-phenotype associations in 34 patients from 28 families, the largest SMARCAL1-associated nephropathy cohort to date. In 11 patients the diagnosis was made unsuspectedly through SRNS gene panel testing. Renal disease first manifested at median age 4.5 yrs, with focal segmental glmerulosclerosis or minimal change nephropathy on biopsy and rapid progression to end-stage kidney disease (ESKD) at median age 8.7 yrs. Whereas patients diagnosed by phenotype more frequently developed severe extrarenal complications (cerebral ischemic events, septicemia) and were more likely to die before age 10 years than patients identified by SRNS-gene panel screening (88 vs. 40%), the subgroups did not differ with respect to age at proteinuria onset and progression to ESKD. Also, 10 of 11 children diagnosed unsuspectedly by Next Generation Sequencing were small at diagnosis and all showed progressive growth failure. Severe phenotypes were usually associated with biallelic truncating mutations and milder phenotypes with biallelic missense mutations. However, no genotype-phenotype correlation was observed for the renal disease course. In conclusion, while short stature is a reliable clue to SIOD in children with SRNS, other systemic features are highly variable. Our findings support routine SMARCAL1 testing also in non-syndromic SRNS.

• MeSH
• Arteriosclerosis diagnosis   genetics   pathology   MeSH
• Child MeSH
• DNA Helicases genetics   MeSH
• Adult MeSH
• Phenotype MeSH
• Genetic Testing MeSH
• Genotype MeSH
• Cohort Studies MeSH
• Infant MeSH
• Kidney pathology   MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Mutation MeSH
• Nephrotic Syndrome diagnosis   genetics   pathology   MeSH
• Osteochondrodysplasias diagnosis   genetics   pathology   MeSH
• Pulmonary Embolism diagnosis   genetics   pathology   MeSH
• Child, Preschool MeSH
• Primary Immunodeficiency Diseases MeSH
• Immunologic Deficiency Syndromes diagnosis   genetics   pathology   MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Child, Preschool MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• DNA Helicases MeSH
• SMARCAL1 protein, human MeSH Browser