OMIM ID:
Coloboma, Microphthalmia, Albinism, and Deafness
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
A 5 year old male has been described with uveal colobomas in microphthalmic eyes plus small corneas with a pannus, dense cataracts, translucent irides, and hypopigmentation of the skin, hair and eyes. A brain MRI showed hypoplasia of the optic nerves and chiasm.
A 9 month old female from another family had severe microphthalmia and small optic nerves. The internal ocular features were not reported.
Systemic Features
The complete phenotype is uncertain since it is based on only two reported and unrelated individuals. The head circumference one one patient was consistent with macrocephaly accompanied by frontal bossing, shallow orbits, preauricular pits and posteriorly rotated ears. A skeletal survey revealed evidence for osteopetrosis. He had a sensorineural hearing deficit said to be congenital in onset.
The other patient, a 9 month old female, belonged to another nonconsanguineous family, and had similar skeletal and craniofacial features with the addition of micrognathia and hypotonia. Congenital neurosensory hearing loss and general lack of pigmentation were noted.
All four parents have congenital sensorineural hearing loss, blue irides and fair skin with premature graying of hair. Four sibs in the two families have phenotypes similar to that of the parents. Only one child, a female, had no features of the phenotype.
Genetics
Inheritance
This condition, so far reported only in a male and a female in unrelated families, is the result of doubly heterozygous mutations in the MITF gene (3p13). One mutation that causes Waardenburg syndrome 2 (WS2A) (193510) is combined with a dominant-negative allele (c.952_954delAGA [p.Arg318del]) to produce the phenotype.
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.