Clinical Characteristics
Ocular Features
Eyelashes are described as ‘long’, and the eyebrows are bushy. The majority of individuals have poor vision secondary to severe receptor dysfunction. Night blindness and severe photophobia are features in some cases. Both retinal and choroidal atrophy have been diagnosed in the first 5 years of life and most patients have a progressive and extensive pigmentary retinopathy.
Systemic Features
Scalp alopecia and sparse body hair is common in spite of the trichomegaly of the eyebrows and eyelashes. Frontal bossing has been noted in some patients. Pituitary dysfunction is suggested by low growth hormone levels, features of hypogonadotropic hypogonadism, and possibly hypothyroidism.
Some deficit of cognitive function is usually present and a few patients have been described as mentally retarded. There is evidence of progressive neurological damage both centrally and peripherally. Developmental milestones are often achieved late and some individuals have been observed to regress during the first decade of life. The peripheral neuropathy includes both sensory and motor components. Sensory nerve action potentials may be lost in the first decade while early motor functions may regress during the same period. Several patients have had evidence of progressive cerebellar ataxia.
Genetics
Inheritance
Compund heterozygous mutations in PNPLA6 (19p13.2), coding for neuropathy target esterase, have been found in several patients presumed to have this condition. Autosomal recessive inheritance has been proposed on the basis of a single family in which an affected brother and sister were born to first cousin parents.
The relationship of this disorder to that found in two cousins, offspring of consanguineous matings, described as ‘cone-rod congenital amaurosis associated with congenital hypertrichosis: an autosomal recessive condition’ (204110 ) is unknown. They were described as having visual impairment from birth and profound photophobia. Fundus changes were minimal with a bull’s eye pattern of pigment changes in the macula described as indicative of a rod-cone congenital amaurosis. ERG responses were unrecordable. These individuals apparently did not have other somatic, psychomotor or neurologic deficits.
Mutations in PNPLA6 occur in other conditions including a form of Bardet-Biedl Syndrome (209900), and Boucher-Neuhauser Syndrome (215470) also known as Chorioretinopathy, Ataxia, Hypogonadism Syndrome 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.