title: Rhombencephalosynapsis and related anomalies: a neuropathological study of 40 fetal cases.
abstract: Rhombencephalosynapsis is an uncommon cerebellar malformation defined by vermian agenesis with fusion of the hemispheres and of the dentate nuclei. Embryologic and genetic mechanisms are still unknown, and to date, no animal models are available. Ultrasound diagnosis is generally suspected after 22 weeks of gestation, and usually the abnormality is suggested by ventriculomegaly. Morphological analysis of 40 fetuses after medical termination of pregnancy allowed us to confirm that rhombencephalosynapsis was always associated with other brain abnormalities or malformations: Purkinje cell heterotopias, fusion of colliculi, forking and/or atresia of the aqueduct and of the third ventricle resulting in a fusion of the thalami, agenesis of the corpus callosum, lobar holoprosencephaly and neural tube defects. Pons and medulla were very infrequently abnormal. Furthermore, complete autopsy made it possible to separate either pure neurologic phenotypes, or associated with extraneural anomalies from syndromic forms: Gomez-Lopez-Hernandez syndrome (1 case) and VACTERL-H syndrome (6 cases). The number of our fetal cases strongly suggests that VACTERL-H association related with rhombencephalosynapsis emerges as a non-random association. Furthermore, recurrence and consanguinity were noted in two different families, which argue for a sporadic or inherited cause. From our results, it could be suggested that rhombencephalosynapsis may be due to defective genes regulating formation of the roof plate and the development of midline cerebellar primordium at the junction of the mesencephalon and of the first rhombomere.
authors.affiliation: Medical Genetics Unit, Rennes University Hospital, Rennes, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Pasquier
authors.forename: Pascale
authors.initials: P
authors.lastname: Marcorelles
authors.forename: Philippe
authors.initials: P
authors.lastname: Loget
authors.forename: Fanny
authors.initials: F
authors.lastname: Pelluard
authors.forename: Dominique
authors.initials: D
authors.lastname: Carles
authors.forename: Marie-Josée
authors.initials: MJ
authors.lastname: Perez
authors.forename: Claude
authors.initials: C
authors.lastname: Bendavid
authors.forename: Céline
authors.initials: C
authors.lastname: de La Rochebrochard
authors.forename: Mathilde
authors.initials: M
authors.lastname: Ferry
authors.forename: Véronique
authors.initials: V
authors.lastname: David
authors.forename: Sylvie
authors.initials: S
authors.lastname: Odent
authors.forename: Annie
authors.initials: A
authors.lastname: Laquerrière
mesh_terms: D000015:Abnormalities, Multiple / Q000196:embryology* / Q000473:pathology; D001921:Brain / Q000002:abnormalities* / Q000196:embryology / Q000473:pathology; D002531:Cerebellum / Q000002:abnormalities* / Q000196:embryology / Q000473:pathology; D002552:Cerebral Ventricles / Q000002:abnormalities* / Q000196:embryology / Q000473:pathology; D019465:Craniofacial Abnormalities / Q000196:embryology / Q000473:pathology; D005260:Female; D005333:Fetus / Q000002:abnormalities*; D006801:Humans; D006849:Hydrocephalus / Q000196:embryology / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D013577:Syndrome