Schimke immuno-osseous dysplasia (SIOD) is a rare multisystem disorder characterized by spondyloepiphyseal dysplasia (SED) resulting in short stature, progressive nephropathy leading to renal failure, and T-cell deficiency. Most affected individuals have distinctive physical features including, fine hair, a thin upper lip, a broad, low nasal bridge, and bulbous nasal tip. Additional features include excessive inward curvature of the lumbar spine, a protruding abdomen, and hyperpigmented macules on the trunk and occasionally on the neck, face, arms and legs. According to the severity of the clinical features and the age of onset, SIOD has been categorized into an infantile or severe early-onset form and a juvenile or milder late-onset form.
The diagnosis of SIOD is based on clinical findings. Life expectancy is limited to childhood or early adolescence in most patients, due to stroke, severe opportunistic infections, bone marrow failure, complications of kidney failure, congestive heart failure, and unspecified lung disease. Those affected with the juvenile form of the condition can survive into adulthood if renal disease is appropriately treated.
Schimke immunoosseous dysplasia is caused by mutations in the SMARCAL1 gene (2q35), which encodes the chromatin remodeling protein hHARP (also known as the SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1). SNF2 related proteins participate in the DNA nucleosome restructuring which commonly occurs during gene regulation and DNA replication, recombination, methylation, and repair. These mutations include gene deletions, nonsense, frame shift, splicing and missense mutations. Patients who have mutations that cause a complete lack of functional protein have a more severe form of this disorder than those who have mutations that lead to an active but malfunctioning protein.
Taha et al. (2004) described a 5-year-old Saudi boy with Schimke immuno-osseous dysplasia born to first-degree cousins. Since birth he had retarded growth and delayed milestones. He had triangular face, thin hair, short neck and trunk with lumbar lordosis, and protruding abdomen, multiple pigmented macules, enlarged nontender and mobile cervical and axillary lymph nodes. His liver extended 3 cm below the costal margin, and he also had bilateral cryptorchidism. A homozygous mutation the SMARCAL1 gene was identified in the affected child.
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