title: Diagnosis of a terminal deletion of 4p with duplication of Xp22.31 in a patient with findings of Opitz G/BBB syndrome and Wolf-Hirschhorn syndrome.
abstract: Opitz G/BBB syndrome (OS) is a congenital midline malformation syndrome characterized by hypertelorism, hypospadias, cleft lip/palate, laryngotracheoesophageal abnormalities, imperforate anus, developmental delay and cardiac defects. The X-linked form is caused by mutations in the MID1 gene, while no gene has yet been identified for the autosomal dominant form. Here, we report on a 15-year-old boy who was referred for MID1 mutation analysis with findings typical of OS, including apparent hypertelorism, hypospadias, a history of feeding difficulties, dysphagia secondary to esophageal arteria lusoria, growth retardation and developmental delay. No MID1 mutation was found, but subsequent sub-megabase resolution array CGH unexpectedly documented a 2.34 Mb terminal 4p deletion, suggesting a diagnosis of WHS, and a duplication in Xp22.31. Wolf-Hirschhorn syndrome (WHS) is a contiguous gene deletion syndrome involving terminal chromosome 4p deletions, in particular 4p16.3. WHS is characterized by typical facial appearance ("Greek helmet facies"), mental retardation, congenital hypotonia, and growth retardation. While the severity of developmental delay in this patient supports the diagnosis of WHS rather than OS, this case illustrates the striking similarities of clinical findings in seemingly unrelated syndromes, suggesting common or interacting pathways at the molecular and pathogenetic level. This is the first report of arteria lusoria (esophageal vascular ring) in a patient with WHS.
authors: Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors: Joyce
authors: J
authors: So
authors: Ines
authors: I
authors: Müller
authors: Melanie
authors: M
authors: Kunath
authors: Susanne
authors: S
authors: Herrmann
authors: Reinhard
authors: R
authors: Ullmann
authors: Susann
authors: S
authors: Schweiger
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics; D000293:Adolescent; D002872:Chromosome Deletion; D002894:Chromosomes, Human, Pair 4; D041321:Chromosomes, Human, X; D004247:DNA / Q000235:genetics; D020440:Gene Duplication; D006801:Humans; D008297:Male; D009693:Nucleic Acid Hybridization; D010375:Pedigree; D013577:Syndrome
chemical_list: D004247:DNA