Clinical Guidance

The early-onset, more severe phenotype has been associated with truncating SMARCAL1 variants that lead to absence of protein product. It has been suggested that compound heterozygous missense variants that result in present but unstable protein may cause a milder nonrenal phenotype. However, no genotype-phenotype correlations have been confirmed; there was no association between type/severity of disease-causing variant and severity of renal disease .

Source: GeneReviews — "Schimke Immunoosseous Dysplasia"

Diagnostic Criteria

No consensus clinical diagnostic criteria for Schimke immunoosseous dysplasia (SIOD) have been published.

Suggestive Findings

SIOD should be suspected in individuals with the following clinical, laboratory, and radiographic features.

Clinical features

Source: GeneReviews — "Schimke Immunoosseous Dysplasia"

Differential Diagnosis

The differential diagnosis of Schimke immunoosseous dysplasia (SIOD) depends on the presenting features in the individual. lists hereditary osteochondrodysplasias associated with nephrotic syndrome; lists hereditary osteochondrodysplasias associated with immune defects. The co-occurrence of disproportionate short stature with spondyloepiphyseal dysplasia, progressive nephropathy, and T cell deficiency is unique to SIOD.

Table 3a.

Differential Diagnosis of Schimke Immunoosseous Dysplasia: Hereditary Osteochondrodysplasias Associated with Nephrotic Syndrome

Gene | Syndrome | MOI | Comment

IFT140

| Conorenal syndrome (OMIM 266920) | AR | Cone shaped epiphyses w/constricted short ribs; retinal disease; renal pathology of variable causes (vs in SIOD, in which the cause is nephrotic syndrome); lack o...

Source: GeneReviews — "Schimke Immunoosseous Dysplasia"

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with Schimke immunoosseous dysplasia (SIOD), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with Schimke Immunoosseous Dysplasia

Source: GeneReviews — "Schimke Immunoosseous Dysplasia"

Clinical Guidance

Avoid the following:

• Hypertension. Poor blood pressure control can exacerbate or evoke cerebral ischemia. In particular, the hypertension arising from using high-dose steroids for empiric treatment of the nephrotic syndrome can evoke cerebral ischemia.

• Heat, stress, and lack of sleep. Individuals with transient neurologic attacks that are not of an ischemic origin have found that heat, stress, and lack of sleep can precipitate the attacks.

• Vaccinations with live vaccines. The T cell deficiency is substantial and there have been serious infections in some individuals. Therefore, in those with T cell immunodeficiency, vaccination with all live vaccines should be avoided, including rotavirus, measles-mumps-rubella (MMR), varicella, bacillus Calmette-Gurin (BCG), oral Salmonella typhi, and yellow fever virus vaccines.

Note: Cells from individuals with SIOD and model organisms are hypersensitive to DNA-damaging agents [, , , , , , ].

Source: GeneReviews — "Schimke Immunoosseous Dysplasia"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Schimke Immunoosseous Dysplasia"

Surveillance Guidelines

Table 6. Recommended Surveillance for Individuals with Schimke Immunoosseous Dysplasia

Source: GeneReviews — "Schimke Immunoosseous Dysplasia"