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Schimke Immunoosseous Dysplasia.

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GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
2002 Oct 1 [updated 2016 Feb 11].

Author information

1
Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada
2
Department of Pediatrics, Division of Allergy, Immunology, and Rheumatology, Stanford University School of Medicine, Stanford, California
3
Department of Neuropediatrics, Children’s Hospital, University of Bochum, Bochum, Germany

Excerpt

CLINICAL CHARACTERISTICS:

Schimke immunoosseous dysplasia (SIOD) is an autosomal recessive multisystem disorder characterized by spondyloepiphyseal dysplasia (SED) resulting in short stature, nephropathy, and T-cell deficiency. Radiographic manifestations of SED include ovoid and mildly flattened vertebral bodies, small deformed capital femoral epiphyses, and shallow dysplastic acetabular fossae. Adult height is 136-157 cm for men and 98.5-143 cm for women. Nearly all affected individuals have progressive steroid-resistant nephropathy, usually developing within five years of the diagnosis of growth failure and terminating with end-stage renal disease (ESRD). The majority of tested individuals have T-cell deficiency and an associated risk for opportunistic infection, a common cause of death. SIOD involves a spectrum that ranges from an infantile or severe early-onset form with death early in life to a juvenile or milder later-onset form with survival into adulthood if renal disease is appropriately treated.

DIAGNOSIS/TESTING:

The diagnosis of SIOD is established in a proband with the characteristic clinical and radiographic features. Identification of biallelic pathogenic variants in SMARCAL1 on molecular genetic testing establishes the diagnosis if clinical features are inconclusive.

MANAGEMENT:

Treatment of manifestations: Renal transplantation as indicated using mild immunosuppressive therapy; hip replacement as needed in older individuals; granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor for neutropenia; bone marrow transplantation as indicated; immunosuppressive therapy for those with autoimmune manifestations; acyclovir for recurrent herpetic infections; imiquimod and cidofovir for severe disseminated cutaneous papilloma virus infections; agents that improve blood flow or decrease coagulability to treat transient ischemic attacks or strokes; standard treatment for hypothyroidism. Prevention of secondary complications: Vaccinations according to the protocol for other T-cell immunodeficiencies (i.e., an avoidance of live attenuated vaccines) in individuals with severe early-onset disease; prophylaxis against Pneumocystis jirovecii pneumonia; prophylactic acyclovir or valacylovir if recurrent oral herpetic infections or shingles occur. Surveillance: Regular monitoring of the hips; annual monitoring of renal, immune, and hematologic status. Agents/circumstances to avoid: Hypertension; heat, stress, and lack of sleep; live attenuated immunizations in those who are T-cell deficient; DNA damaging anti-cancer therapies.

GENETIC COUNSELING:

SIOD is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing and prenatal testing are possible if both pathogenic variants in the family are known.

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