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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.
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.
This is an autosomal dominant disorder 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 as transportation of other intracellular organelles.
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.
No treatment is known.
The ocular phenotype has not been well defined in this condition since few families have been reported. Microphthalmia is present in some patients. The corneas may be small and there is often some conjunctival growth over the limbus.
The retinal features consist of lacunar depigmentation of the RPE and in some cases resemble the lesions of congenital toxoplasmosis. Eighty to 90 per cent of patients have areas of atrophic and dysplastic-appearing lesions of the retina and choroid with vascular attenuation. The edges of lacunae may have patchy hyperpigmentation. These lesions are usually static but may show mild progression. Visual acuity is generally stable or only mildly progressive. However, other patients have a severe reduction in acuity. ERG responses are reduced.
The amount of microcephaly may be minimal and at least some patients have ‘bulging’ foreheads. The amount of mental deficiency varies from mild to severe. IQ levels are generally in the range of 60-70. Hypotonia has been reported in more severe cases. Skull size is usually 2-3 standard deviations below the mean and generally has some frontal prominence.
This seems to be an autosomal dominant disorder although no loci or mutations have been identified. It is likely that the category of disease known as microphthalmia-chorioretinal dysplasia consists of a heterogeneous group of disorders. For other disorders in this database having a somewhat similar phenotype see: microcephaly, lymphedema, chorioretinopathy syndrome (152950) and the microcephaly with chorioretinopathy, AR syndrome (251270). As yet no universally acceptable criteria have been proposed to delineate these entities.
Treatment is supportive. Low vision aids may be helpful.