Hirschsprung disease in an infant with a contiguous gene syndrome of chromosome 13

Hirschsprung disease is a developmental disorder resulting from the arrest of the craniocaudal migration of enteric neurons from the neural crest alon g gastrointestinal segments of variable length; see Behrman [Nelson textboo k of pediatrics, 1992:954-956]. It is a heterogeneous disorder in which fam ilial cases map to at least three loci whose function is necessary for norm al neural crest-derived cell development. Homozygous mutations in the endot helin-B receptor gene (EDNRB) on 13q22 have been identified in humans and m ice with Hirschsprung disease type 2 (HSCR2). The auditory pigmentary disor der, Waardenburg-Shah syndrome, comprises Waardenburg syndrome and Hirschsp rung disease and has also been mapped to the EDNRB locus. Hirschsprung dise ase, malrotation, isochromia, a profound sensorineural hearing loss, and se veral other anomalies were found in an infant with an interstitial deletion of 13q, suggesting the existence of a contiguous gene syndrome involving d evelopmental genes necessary for the normal growth of the neural crest deri vatives of the eye, inner ear, and colon. We report on an additional patien t with a deletion in 13q and Hirschsprung disease. Congenital anomalies ass ociated with deletions of the distal long arm of chromosome 13 are sufficie ntly consistent to suggest a clinical syndrome. (C) 2001 Wiley-Liss, Inc.