title: CHARGE syndrome: report of 47 cases and review.
abstract: The acronym CHARGE refers to a syndrome of unknown cause. Here we report on 47 CHARGE patients evaluated for the frequency of major anomalies, namely coloboma (79%), heart malformation (85%), choanal atresia (57%), growth and/or mental retardation (100%), genital anomalies (34%), ear anomalies (91%), and/or deafness (62%). In addition, we comment on anomalies observed very frequently in neonates and infants with the CHARGE syndrome, including, minor facial anomalies, neonatal brain stem dysfunction with cranial nerve palsy, and, mostly, internal ear anomalies such as semicircular canal hypoplasia that were found in each patient that could be tested. We propose several criteria for poor survival including male gender, central nervous system and/or oesophageal malformations, and bilateral choanal atresia. No predictive factor regarding developmental prognosis could be identified in our series. A significantly higher mean paternal age at conception together with concordance in monozygotic twins and the existence of rare familial cases support the role of genetic factors such as de novo mutation of a dominant gene or subtle sub-microscopic chromosome rearrangement. Finally, the combination of malformations in CHARGE syndrome strongly supports the view that this multiple congenital anomalies/mental retardation syndrome is a polytopic developmental field defect involving the neural tube and the neural crests cells.
authors.affiliation: Département de Génétique et Unité de Recherches sur les Handicaps Génétiques de l'Enfant, INSERM U-393, Hôpital Necker-Enfants-Malades, Paris, France.
authors.forename: A L
authors.initials: AL
authors.lastname: Tellier
authors.forename: V
authors.initials: V
authors.lastname: Cormier-Daire
authors.forename: V
authors.initials: V
authors.lastname: Abadie
authors.forename: J
authors.initials: J
authors.lastname: Amiel
authors.forename: S
authors.initials: S
authors.lastname: Sigaudy
authors.forename: D
authors.initials: D
authors.lastname: Bonnet
authors.forename: P
authors.initials: P
authors.lastname: de Lonlay-Debeney
authors.forename: M P
authors.initials: MP
authors.lastname: Morrisseau-Durand
authors.forename: P
authors.initials: P
authors.lastname: Hubert
authors.forename: J L
authors.initials: JL
authors.lastname: Michel
authors.forename: D
authors.initials: D
authors.lastname: Jan
authors.forename: H
authors.initials: H
authors.lastname: Dollfus
authors.forename: C
authors.initials: C
authors.lastname: Baumann
authors.forename: P
authors.initials: P
authors.lastname: Labrune
authors.forename: D
authors.initials: D
authors.lastname: Lacombe
authors.forename: N
authors.initials: N
authors.lastname: Philip
authors.forename: M
authors.initials: M
authors.lastname: LeMerrer
authors.forename: M L
authors.initials: ML
authors.lastname: Briard
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: S
authors.initials: S
authors.lastname: Lyonnet
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis*; D002490:Central Nervous System / Q000002:abnormalities; D002648:Child; D002675:Child, Preschool; D002754:Choanal Atresia / Q000175:diagnosis; D003051:Cochlea / Q000002:abnormalities; D003103:Coloboma / Q000175:diagnosis; D003391:Cranial Nerves / Q000002:abnormalities; D003638:Deafness / Q000175:diagnosis; D004423:Ear / Q000002:abnormalities; D005145:Face / Q000002:abnormalities; D005183:Failure to Thrive / Q000175:diagnosis; D005260:Female; D005835:Genitalia / Q000002:abnormalities; D006330:Heart Defects, Congenital / Q000175:diagnosis; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011379:Prognosis; D013577:Syndrome; D014722:Vestibule, Labyrinth / Q000002:abnormalities