CNS dysplasia in dysencephalia splanchnocystica (Gruber's syndrome)

Abstract

A macrosomic male infant with multiple malformations survived for 4 days. His external dysplasias comprised macrocephalus, cheilopalatoschisis, auricular anomalies, and unilateral hexadactyl; his internal dysplasias included cysts of kidneys and pancreas, and a patent foramen ovale. The child had frequent generalized convulsions and died of bronchopneumonia. Chromosomal analysis was normal. The main neuropathological findings were a cleft foramen magnum, micropolygria and heterotopia of the neocerebrum, hypoplasia of the vermis and central white matter of the cerebellum, diffuse heterotopia of Purkinje cells, and unique heterotopic gray matter in the central cervical cord. The infant's disorder was classified as Gruber's syndrome, and this report may be the first detailed description of CNS malformations in this syndrome which, however, are probably not specific for this syndrome. The neuropathological findings were compatible with a heterochronic pathogenesis. this and the familial occurrence of malformations suggest a genetic nature of the syndrome.

Descriptive epidemiology of holoprosencephaly and arhinencephaly in metropolitan Atlanta, 1968–1992

“…Although we identified no infants with HPE associated with trisomy 21 as others have reported [Pi et al, 1980;Urioste et al, 1988;Epstein et al, 19881, the unavailability of cytogenetic information on all case infants does not allow us to provide any evidence of whether or not an association exists [Martinez-Frias, 19891. We categorized four case infants as having singlegene conditions. One case infant with AR had Meckel syndrome; this condition has previously been associated with HPEIAR [Opitz and Howe, 1969;Hsia et al, 1971;Hori et al, 1980;Leech and Shuman, 1986; Ahdab-Barmada and Claassen, 19901. One infant with HPE had short-rib polydactyly of the Saldino-Noonan type.…”

Dandy–Walker malformation in the Meckel syndrome

“…Although encephalocele, usually in the occipital region, is the classical and most frequently reported neurological component of the Meckel syndrome, phenotypic variation in CNS malformations, as in the syndrome as a whole, is extensive with upward of 25 separate neurological anomalies described to date [Hori et al, 1980;Aleksic et al, 19841. Cerebellar malformations are common, in particular hypoplasia or aplasia of the midline vermis, but in no case since the syndrome was first described has the presence of the DWM been reported.…”

A new syndrome with features of the Smith‐Lemli‐Opitz and Meckel‐Gruber syndromes in a sibship with cerebellar defects

“…Our patient 1 had no hepatic abnormalities; the status of patient 2 in this regard is unknown, and patient 3 showed periportal fibrosis and bile duct accentuation. Cerebellar defects have beeen described infrequently in the SLOS and have included persistence of the external granular layer of the cerebellum [40], hypoplasia [ 1251, asymmetry and increased weight [24], compression atrophy [ 11 11, and partial vermis agenesis [21, 531. In comparison, cerebellar anomalies are more frequent in the MS, with 38 cases noted [3,34,48,60,69,70,73,78,95,98,102,103,106,112,118,122,126,1301, with six having agenesis or hypoplasia of the vermis [3, 69, 95, 1031. In 1969, Joubert et a1 [75] described four sibs born to parents who were remotely consanguineous; two of these sibs had partial and two complete agenesis of the cerebellar vermis. Associated findings were hypotonia, strabismus, mental retardation, periodic breathing, opsoclonus, ataxia, and seizures.…”