OMIM ID:
Chorioretinal dysplasia, lymphedema, and microcephaly
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
The congenital lymphedema results in thickened and ptotic eyelids with prominent epicanthal folds. Congenital ptosis is not uncommon in the general population in the absence of lymphedema so that this feature by itself is insufficient to diagnose this syndrome. Retinal folds with variable degrees of pigmentary changes are often present. Narrowed retinal vessels, atrophic nerve heads and progressive chorioretinopathy have been reported. Visual acuity is often reduced, sometimes severely, and nystagmus may be present.
Systemic Features
Coarse hair follicles over the dorsum of the hands and feet and white nails when combined with the thickened, ptotic eyelids suggest the presence of lymphedema. The hair pattern is often altered on the arms, nape of the neck, and the back. White lines in the palms are also suggestive. The ‘facial phenotype’ includes full cheeks, flat nasal bridge and underdeveloped supraorbital ridges, up slanting palpebral fissures, broad nose with rounded tip, anteverted nares, and a long philtrum, thin upper lip, and sometimes micrognathia. The ears may appear large. Children with this syndrome are often hypotonic during the newborn period but this feature is less evident later in childhood and improves more rapidly than the resolution of the lymphedema. The lymphedema usually improves during early childhood and is often confined to the dorsum of the hands and feet at that time. Psychomotor development is variably delayed and some but not all patients are mentally retarded. Microcephaly is a consistent feature.
Not all features are present in all patients and, specifically, there are often microcephalic relatives who lack other signs.
Genetics
Inheritance
This is an autosomal dominant disorder which may consist of more than one entity but at least some cases result from heterozygous mutations in KIF11 (10q23.33). The gene encodes a member of the kinesin family of proteins responsible for cytoplasmic mechanisms that are essential for spindle assembly and function as well in transportation of other intracellular organelles. Mutations in this gene have also been implicated in familial exudative vitreoretinopathy (FEVR) and there is phenotypic overlap with the condition described here.
It is not unusual for microcephalic individuals to also have chorioretinal dysplasia and/or pigmentary retinopathy. See microcephaly, chorioretinal dysplasia, mental retardation (156590), for a somewhat similar autosomal dominant condition, as well as microcephaly with chorioretinopathy, AR (251270) for an autosomal recessive condition with this combination. Neither of these conditions is associated with congenital lymphedema, however.
Pedigree
Autosomal dominant
Autosomal dominant disorders require only one mutation for the disease to be expressed. Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease. It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).
Autosomal dominant inheritance leads to a vertical pattern of transmission