UC Irvine

Kousseff syndrome was originally described by Boris Kousseff in 1984: Pediatrics 74:395-398 in three siblings whose main features were conotruncal heart defects, neural tube defects, and dysmorphic features. The proband is a white male who has spina bifida, shunted hydrocephalus, cleft palate, short stature, cognitive impairment, and the typical craniofacial features of velo-cardio-facial syndrome (VCFS), including low-set and dysplastic ears, broad base of the nose, narrow alae nasi, and retrognathia. The family history is significant for a brother who died at 2 weeks of age with myelomeningocele, hydrocephalus, transposition of the great vessels, and unilateral renal agenesis, and a sister who died at 11 days of age with myelomeningocele, truncus arteriosus, hypocalcemia, and autopsy findings of absent thymus and parathyroid glands, consistent with DiGeorge anomaly. Given the clinical findings, family history, and recent knowledge that open neural tube defects can occur in VCFS/DiGeorge anomaly, FISH analysis for 22q11-13 deletion was performed on the proband. A deletion was detected in him and subsequently confirmed in his father. Molecular analysis on autopsy material confirmed the deletion in the proband's deceased brother. We suggest that individuals with neural tube defects associated with other anomalies such as congenital heart defects or cleft palate be evaluated for 22q deletions.