Möbius sequence, Robin complex, and hypotonia: severe expression of brainstem disruption spectrum versus Carey-Fineman-Ziter syndrome.
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.
Verloes
Alain
A
Clinical Genetic Unit, Hospital Robert Debré, Paris, France. Alain.verloes@rdb.ap-hop-paris.fr
Bitoun
Pierre
P
Heuskin
Anne
A
Amrom
Dina
D
van de Broeck
Hilde
H
Nikkel
Sarah M
SM
Chudley
Albert E
AE
Prasad
Asuri N
AN
Rusu
Cristina
C
Covic
Mircea
M
Toutain
Annick
A
Moraine
Claude
C
Parisi
Melissa A
MA
Patton
Michael
M
Martin
Jean-Jacques
JJ
Van Thienen
Marie-Noelle
MN
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