OMIM ID:
Chorioretinopathy, Ataxia, and Hypogonadism
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
The retinal pigment epithelium changes may be seen as early as the first decade of life with pigment deposition resembling bone spicules. These changes as well as atrophy of the choriocapillaris are most apparent in the posterior pole and extend into the midperiphery. Retinal vessels may be attenuated. Progressive loss of vision, dyschromatopsia, and photophobia are the primary ocular symptoms. Night blindness and constricted visual fields are noted by some patients. The ERG shows subnormal and sometimes absent photopic and scotopic responses. Nystagmus is present in more than half of individuals.
Systemic Features
Difficulties with balance, intention tremors, and scanning speech are evident in adolescence or early adult life. Cerebellar ataxia is present in nearly 40 percent of individuals. However, there is marked variability in the rate of progression. Many patients have atrophy of the superior and dorsal areas of the cerebellar vermis and atrophy of the cerebellar hemispheres as noted on MRIs. Hypogonadotrophic hypogonadism is a feature with delayed puberty noted in 26 percent. In the absence of exogenous hormone administration, secondary sexual characteristics fail to develop.
Genetics
Inheritance
Autosomal recessive inheritance has been suggested on the basis of consanguinity in three families, multiple affected sibs born to normal parents, and a 1:1 sex ratio. Homozygous and compound heterozygous mutations in PNPLA6 (19p13.2) have been found in several patients.
Mutations in PNPLA6 occur in other conditions including a form of Bardet-Biedl Syndrome (209900), and Trichomegaly Plus Syndrome (275400), in this database.
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.