Möbius sequence, Robin complex, and hypotonia: Severe expression of brainstem disruption spectrum versus Carey-Fineman-Ziter syndrome

• Published in: American journal of medical genetics 2004-06, Vol.127A (3), p.277-287
• Main Authors: Verloes, Alain, Bitoun, Pierre, Heuskin, Anne, Amrom, Dina, Van de Broeck, Hilde, Nikkel, Sarah M., Chudley, Albert E., Prasad, Asuri N., Rusu, Cristina, Covic, Mircea, Toutain, Annick, Moraine, Claude, Parisi, Melissa A., Patton, Michael, Martin, Jean-Jacques, Van Thienen, Marie-Noelle
• Format: Article
• Language: English
• Subjects: Abnormalities, Multiple - physiopathology; Biological and medical sciences; Brain Stem - physiopathology; brainstem disruption; Carey-Fineman-Ziter syndrome; Female; General aspects. Genetic counseling; Humans; Infant, Newborn; Male; Medical genetics; Medical sciences; Mobius Syndrome - physiopathology; Muscle Hypotonia - physiopathology; Möbius sequence; nosology; Pierre Robin Syndrome - physiopathology; Poland anomaly; Robin sequence; Syndrome
• ISSN: 1552-4825; 0148-7299; 1552-4833; 1096-8628
• DOI: 10.1002/ajmg.a.20687

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. © 2004 Wiley‐Liss, Inc.