Genetics of the Meckel Syndrome (Dysencephalia Splanchnocystica)

Seven cases in two families are reported of the Meckel syndrome; two sets of male identical twins in one family, and three affected siblings in another. The key features of this syndrome are occipital encephalocele, cleft lip and palate, polydactyly, and polycystic kidneys. Additional malformations frequently found include microcephaly, micrognathia, absence of the olfactory lobes, microphthalmia, absent pituitary with consequent thyroid hypoplasia and suprarenal agenesis, short-limbed dwarfism, microgenitalia or ambiguous genitalia, and accessory spleen. No chromosomal abnormality has been found in this syndrome, although it is otherwise remarkably similar to the trisomy D1 syndrome. More than 50 cases have been described in the literature that are recognizable as having the Meckel syndrome. Almost half of these were familial, being clustered in sibships. Eight cases tested have all had normal chromosomes. The concordant involvement of identicial twins, and consanguinity of some parents provide further evidence strongly supporting the hypothesis that the Meckel syndrome is a recessively inherited condition which is determined by homozygous expression of a single autosomal gene. Recognition of this syndrome is important for proper genetic counseling of parents having this risk. This mutant gene may disrupt normal fetal development by affecting an embryonic organizer system.