title: Möbius sequence, Robin complex, and hypotonia: severe expression of brainstem disruption spectrum versus Carey-Fineman-Ziter syndrome.
abstract: We report on nine unrelated children fitting a diagnosis of Carey-Fineman-Ziter syndrome (CFZS). All children presented with Möbius sequence, Pierre Robin complex (6/9) or micrognathia, and hypotonia. Some had primary hypoventilation, delayed development, and acral anomalies. The neuropathological investigations performed in two patients showed a combination of dysplastic lesions (neuronal heterotopias) and encephaloclastic changes consisting of small foci of necrosis with microcalcifications. The mother of a third child had severe trauma during her 2nd month of pregnancy. Based on a review of the literature on MS and CFZS, we suggest designating as "Robin-Möbius phenotype" a distinct clinical variant of MS with extensive brainstem involvement, Robin complex, hypotonia without specific muscle disorder, clubfeet and variable acral anomalies. This condition appears to bear a higher risk of mental handicap and perhaps a higher recurrence risk than "common" MS. Neuropathology and neuroimaging are suggestive, at least in some cases, of a vascular disruption, which could be exogenous, or secondary to a genetic predisposition. Etiologic heterogeneity seems likely and, in that respect, the original CFZS family could represent a private syndrome fitting on the "Robin-Möbius" spectrum. Despite the existence of two familial reports, recurrence risk is probably much lower than 25%, although exact figures cannot be extracted from the available literature.
authors.affiliation: Clinical Genetic Unit, Hospital Robert Debré, Paris, France. Alain.verloes@rdb.ap-hop-paris.fr
authors.forename: Alain
authors.initials: A
authors.lastname: Verloes
authors.forename: Pierre
authors.initials: P
authors.lastname: Bitoun
authors.forename: Anne
authors.initials: A
authors.lastname: Heuskin
authors.forename: Dina
authors.initials: D
authors.lastname: Amrom
authors.forename: Hilde
authors.initials: H
authors.lastname: van de Broeck
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Nikkel
authors.forename: Albert E
authors.initials: AE
authors.lastname: Chudley
authors.forename: Asuri N
authors.initials: AN
authors.lastname: Prasad
authors.forename: Cristina
authors.initials: C
authors.lastname: Rusu
authors.forename: Mircea
authors.initials: M
authors.lastname: Covic
authors.forename: Annick
authors.initials: A
authors.lastname: Toutain
authors.forename: Claude
authors.initials: C
authors.lastname: Moraine
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Parisi
authors.forename: Michael
authors.initials: M
authors.lastname: Patton
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Martin
authors.forename: Marie-Noelle
authors.initials: MN
authors.lastname: Van Thienen
mesh_terms: D000015:Abnormalities, Multiple / Q000503:physiopathology*; D001933:Brain Stem / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D020331:Mobius Syndrome / Q000503:physiopathology*; D009123:Muscle Hypotonia / Q000503:physiopathology*; D010855:Pierre Robin Syndrome / Q000503:physiopathology*; D013577:Syndrome