Phenotypic variability in Meckel–Gruber syndrome

Abstract

Five Bedouin sibs are described with Meckel‐Gruber syndrome (MGS), an autosomal recessive disorder with multiple abnormalities. Each affected sib manifested only two of the three cardinal signs of MGS: occipital encephalocele and polycystic kidneys, lacking polydactyly. The phenotypic variability of the MGS pleiotropic gene is briefly discussed.

Meckel–Grüber syndrome: sonography and pathology

“…Inadequate tissue recognition or lack of corporeal determinism have been suggested7, 14. Genetic mapping of the syndrome is still incomplete and several loci have been proposed, which may, in part, explain the observed phenotypic variability8, 9, 15; this variability has been underlined in many reports3, 6, 16–18, particularly the study of 67 cases by Salonen16.…”

Meckel–Gruber Syndrome: a population-based study on prevalence, prenatal diagnosis, clinical features, and survival in Europe

“…9 There is evidence that the prevalence is higher in populations with higher consanguinity rates, as in India, 8,10 Pakistan, 11 Kuwait and other Arab countries. 12,13 In Europe, high rates were found in Belgium 14 and in Finland, 15 but there are currently no population-based epidemiologic data available for Europe or worldwide.…”

Combination of Cor Triatriatum Sinistrum and Hypoplastic Left Heart Syndrome in Meckel-Gruber Syndrome: A Case Report

“…The most frequent findings include central nervous malformations with occipital encephalocele (90% of cases), cerebral and cerebellar hypoplasia, and microphthalmia; facial abnormalities with sloping forehead, cleft palate, and micrognathia; ductal plate abnormality of the liver; multicystic dysplastic kidneys (100%); and postaxial polydactyly (83%). Less common abnormalities include Dandy-Walker malformation, midline cleft lip, cleft epiglottis, neonatal teeth, webbed neck, gut malrotation, external genital ambiguity in males, syndactyly, clinodactyly, club feet, short limb, and single umbilical artery [3,7,9,15]. Minimum criteria for diagnosis of MKS have been suggested as at least 2 of the following: bilateral cystic renal dysplasia, hepatic ductal plate malformation, neural tube defects, and postaxial polydactyly [7]; some reports do not include the hepatic lesion [8,10].…”

“…The identification of causative genes in some of these syndromes has provided new insight both into the variability of specific syndromes and the relationships between different syndromes. In the case of MKS, the wide variety of clinical features can be explained partly by genetic heterogeneity [5,15,35,36]. To date, six loci are associated with MKS: MKS1 (on 17q21-24), MKS3/ TMEM67 (on 8q22.1), MKS4/CEP290 (on 12q21.32), MKS5/RPGRIP1L (on 16q12.2), and MKS6/CC2D2A (on 4p15.3) [3,23,37,38].…”