OMIM ID:
Chorioretinopathy with Microcephaly 1
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
The ocular features have not been well described. Small corneas, hyperopia, pale optic nerves and a variety of pigmentary changes in the retina have been reported. The latter may consist of diffuse, fine or granular pigmentary changes. Areas of pigmentary atrophy are often associated with patchy areas of pigmentary clumping. These changes are usually located posterior to the equator. Choroidal vessels may be sparse where the RPE is absent. It has been suggested that the patchy pattern of retinal pigmentation resembles ocular toxoplasmosis. Strabismus is common. One report suggests microphthalmos in a patient. Vision has been reported as subnormal from the first year of life but no quantitative data are available.
Systemic Features
Microcephaly is a consistent feature. The forehead is steeply sloped but facial size appears normal. The palate is highly arched. Patients often have hyperactive deep tendon reflexes and walk with a shuffling gait. Children are often hyperactive and highly social. Intelligence quotients are usually subnormal. No lymphedema has been reported. At least some patients have cutis marmorata.
On MRI diffuse pachygryria is seen. The vermis is hypoplastic and the surface area of the corpus callosum is reduced to half of normal.
Genetics
Inheritance
Parental consanguinity was present in two reported families and pedigrees are consistent with autosomal recessive inheritance with homozygous mutations of TUBGCP6 (22p22) responsible.
This presumed recessive disorder appears to be different than the autosomal dominant disorder of lymphedema, microcephaly, and chorioretinal dysplasia (MCLMR) (152950) although molecular confirmation is lacking.
For somewhat similar disorder see Chorioretinopathy with Microcephaly 2 (616171).
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.