OMIM ID:
Meckel Syndrome
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
The ocular phenotype is highly variable. The globe is often malformed or may be clinically absent. Cryptophthalmos, clinical anophthalmia, and microphthalmos with sclerocornea and microcornea have been reported. Posterior staphylomas, retinal dysplasia, partial aniridia, cataracts, and hypoplasia or absence of the optic nerve are sometimes seen. Some patients have incompletely formed eyes with shallow anterior chambers, angle anomalies, and a persistent tunica vasculosa with lens opacification. Histopathology may reveal thinning of the nerve fiber layer and a paucity of retinal ganglion cells. The retina has been described as dysplastic with foci of rosette-like structures and abundant glial cells.
Systemic Features
Meckel or Meckel-Gruber syndrome is a clinically and genetically heterogeneous group of disorders with severe multisystem manifestations. The triad of cystic renal disease, polydactyly (and sometimes syndactyly), and a skull malformation (usually an encephalocele) is considered characteristic of MKS. However, these signs are variable and only about 60% of patients have all three features. Many patients have additional signs such as malformations of the biliary tree, cleft palate (and/or lip), sloping forehead, low-set ears, short neck, low-set ears, ambiguous genitalia, and short, bowed limb bones. Pulmonary hypoplasia is common which, together with kidney and liver disease, is responsible for the poor prognosis of most infants.
Many clinical abnormalities resemble those present in the Smith-Lemli-Opitz syndrome (270400) and in Joubert syndrome (213300).
Genetics
Inheritance
Most conditions in this group are inherited in an autosomal recessive pattern. Mutations in 9 genes have been identified as responsible for some variant of MKS in which there is a considerable range of clinical expression. There is significant clinical overlap with Joubert syndrome and it is not surprising that at least 5 of these mutations have been identified in both conditions. Further nosological confusion is generated by those who consider patients with the severe, lethal phenotype to have Meckel syndrome while those with milder disease are labeled Joubert syndrome, regardless of genotype.
Rare heterozygotes have been reported with isolated features such as polydactyly.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.