SMARCAL1 mutations: a cause of prepubertal idiopathic steroid-resistant nephrotic syndrome

Pediatr Res. 2009 May;65(5):564-8. doi: 10.1203/PDR.0b013e3181998a74.


Schimke immuno-osseous dysplasia (SIOD) is a rare autosomal-recessive multisystem disorder with disproportionate growth failure, impaired T cell function, and steroid-resistant nephrotic syndrome. Recently, we presented the typical anthropometric features of SIOD. We now present data on two siblings who were initially classified as suffering from familial steroid-resistant nephrotic syndrome of unknown genetic origin. Apart from growth failure, no syndrome-specific symptoms were found until the age of 10 y. However, serial anthropometric examinations showed the development of a SIOD-like pattern with a decreased ratio of trunk to leg length in early adolescence. The growth pattern was significantly different from that seen in children with chronic renal failure of other origins. In prepuberty the siblings had proportionate short stature but developed disproportion only during adolescence. Molecular genetic analysis revealed compound heterozygosity for a known and a new mutation in the SMARCAL1 gene.

Conclusion: the disease spectrum associated with SMARCAL1 mutations includes previously undescribed milder phenotypes that may be clinically overlooked, particularly before puberty. Serial anthropometric assessment can eventually identify patients with a growth pattern similar to that of SIOD. These patients should be tested for SMARCAL1 mutations to avoid overtreatment with immunosuppressive agents.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • DNA Helicases / genetics*
  • DNA Mutational Analysis
  • Drug Resistance*
  • Female
  • Genetic Predisposition to Disease
  • Growth Disorders / genetics
  • Hip Dislocation, Congenital / genetics
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Kidney Transplantation
  • Mutation*
  • Nephrotic Syndrome / diagnosis
  • Nephrotic Syndrome / genetics*
  • Nephrotic Syndrome / therapy
  • Phenotype
  • Renal Dialysis
  • Risk Factors
  • Sexual Development*
  • Steroids / therapeutic use*
  • Treatment Failure
  • Young Adult


  • Immunosuppressive Agents
  • Steroids
  • SMARCAL1 protein, human
  • DNA Helicases