Phenotypic variation in Meckel syndrome

Abstract

Four sibs are described with Meckel syndrome, an autosomal recessive disorder with multiple abnormalities. Each sib manifested only two of the three cardinal signs of Meckel syndrome ‐ encephalocoele and polycystic kidneys, lacking Polydactyly. The literature is examined to assess the phenotypic variation of the condition: 57 % of cases have all the three major abnormalities, 16% have the two found in this family, and the remainder exhibit other variations. In 9 of 17 families where more than one sib is affected, manifestation between sibs is the same, but in the only other two families with as many as four affected sibs, there is variation in expression between sibs.

Meckel–Grüber syndrome: sonography and pathology

“…The first reports included the association of occipital encephalocele, microcephaly, cleft palate, polycystic kidneys and polydactyly1. Since then, other anomalies have been added to the description (posterior fossa, face, heart, spleen, digestive tract, genital tract and limb anomalies)3–6. Phenotypic variability is well‐described even among siblings presenting a recurrence of the disease, rendering a precise diagnosis difficult.…”

Phenotypic variability in Meckel–Gruber syndrome

“…Phenotypic and survival variations of MGS and partial expression in sibships are well documented (Mecke & Passarge 1971, Fitch & Pinsky 1973, Fraser & Lytywn 1981, Seller 1981, Lowry et al 1983, Rapola & Salonen 1985. In a survey of 49 MGS cases, Mecke & Passarge (1971) noted wide phenotypic variability of the MGS gene.…”

“…The fact that polydactyly is lacking in the five Bedouin sibs is quite unusual (P=0.05), and with the lack of most of the "associated" features it raises the question of a possible allelic difference. Sibs lacking polydactyly and families with one sib who had polydactyly and one who did not have been reported (Crawford et al 1978, Friedrich et al 1979, Seller 1981and Lurie et al 1984.…”

Mutations inTMEM231cause Meckel–Gruber syndrome

“…The disease is usually lethal shortly after birth, and affected children typically present with the triad of occipital encephalocele, polydactyly, and polycystic kidney disease, among other associated features. 6 Twelve genes are known to cause this disorder when in EVC2 and EXOC4 may also cause MKS. 7 In this study, we show that TMEM231 is the latest gene to be linked to MKS pathogenesis based on pathogenic mutations we identified in two families.…”