Novel Skeletal Features in Siblings with Schimke Immuno-Osseous Dysplasia

Background: Schimke Immuno-Osseous dysplasia (SIOD) due to SMARCAL1 mutation is an autosomal recessive disorder with a prevalence of one in 1 to 3 million. It is characterised by a diagnostic triad of spondyloepiphyseal dysplasia, T-cell immunodeficiency and progressive renal disease.

Objective: To report novel skeletal features in a sibship with genetically confirmed SIOD.

Methods: Case notes were summarised and a review of previously published cases of SIOD was undertaken.

Results: The female proband presented with failure to thrive in infancy and echocardiogram revealed a perimembranous ventricular septal defect (VSD). Marked proteinuria was identified at age 5 and renal biopsy subsequently confirmed Focal-segmental glomerulosclerosis (FSGS). Physical examination was notable for short stature, dysmorphic features, Klippel-Feil syndrome and a Sprengel shoulder. She progressed to end-stage renal failure in adolescence. Her clinical course also included an ischaemic stroke from cerebral vasculopathy, hypothyroidism and T-cell immunodeficiency. Heterozygous c.2114C>T and c.2070+2_3insT mutations in the SMARCAL1 gene were identified. The probands younger brother had incidental detection of mild proteinuria in early adolescence. His physical and skeletal features are similar to those of the proband. He has subclinical hypothyroidism and laboratory evidence of T-cell immunodeficiency. His renal function is currently normal aged 19 years. Genetic analysis confirmed identical mutations to his sister.

Conclusion: To date, no published case has outlined cardiac septal defects as a clinical feature of SIOD. Klippel-Feil syndrome and Sprengel shoulders in patients with SIOD have not been previously described in the literature, but cardiac abnormalities can be a feature of Klippel-Feil syndrome. In addition, this case series describes both a case of early-onset SIOD with multiple, life-threatening co-morbidities and a case of juvenile-onset SIOD with a significantly milder phenotype despite an identical genotype.