OMIM ID:
Chorioretinopathy with Microcephaly 3
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
The eyes are not notably small although several patients have been reported to have significant hyperopia. Vision can be impaired and some individuals have early-onset nystagmus. The ERG responses are attenuated and may be absent. The retina is dysplastic with multiple atrophic punched-out lesions, attenuated retinal vessels, and sparse pigmentation. Large retinal folds have been described and one patient developed a retinal detachment. Optic atrophy was noted in one individual.
Systemic Features
Microcephaly of 3-4 standard deviations below normal is a constant feature. Motor and language abilities can be mildly delayed and several patients have had mild learning difficulties. Brain imaging has been normal in most individuals but a shortened and thin corpus callosum was present in one patient.
Genetics
Inheritance
Family and genetic evidence suggest autosomal recessive inheritance. Compound heterozygous mutations in the TUBGCP4 gene (15q15.3) code for part of a protein complex involved in microtubule organization.
For a somewhat similar condition with a different mutation involving the same microtubule complex see Chorioretinopathy with Microcephaly 1 (251270).
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.