Patients with Schinzel-Giedion syndrome (SGS) have characteristic facial features, midface retraction, skull anomalies abnormal genitalia, and cardiac and renal malformations. SGS is a lethal condition, as most patients die in infancy of respiratory failure or infections. Most patients have profound developmental delay. Characteristic facial features include large fontanelles, prominent forehead, hypertelorism, shortened and retracted midface, macroglossia, and a short neck. Failure to thrive, seizures, vision and hearing problems are also very common. Patients with SGS also have an increased risk for tumors, particularly neuroepithelial neoplasia.
Mutations of the SETBP1 gene were identified in four patients with SGS by whole exome sequencing. Additional sequencing of the SETBP1 gene in individuals with SGS identified mutations in 8/9. All 13 patients in this study met Lehman’s diagnostic criteria (see information sheet). SETBP1 has 6 coding exons and all mutations reported to date have been de novo missense mutations within a stretch of 11 base pairs in exon 4.