Clinical Characteristics
Ocular Features
Persistence and hyperplasia of the embryonic vitreous in most individuals results in significant ocular morbidity. It results from a transcription factor deficiency in retinal ganglion cells which in turn negatively impacts development of the retinal vasculature. As a consequence, the fetal hyaloid vasculature fails to regress and its persistence leads to a retrolental mass.
PHPV usually occurs unilaterally and affected eyes are generally blind from birth. Leukocoria secondary to the presence of a retrolental fibrovascular stalk is easily visible. Nystagmus is frequently present and some patients have microphthalmos. The anterior segment may also be involved as evidenced by the presence of peripheral anterior synechiae, corneal opacities, cataracts, and glaucoma. Contracture of the retrolental tissue In the posterior chamber results in the ciliary processes being pulled centrally and can lead to hemorrhage and retinal detachment.
The clinical manifestations can make it difficult to distinguish from Norrie disease.
Systemic Features
No consistent systemic signs have been reported in PHPV individuals.
Genetics
Inheritance
The majority of PHPV cases occur sporadically, but families with transmission patterns compatible with both autosomal recessive and autosomal dominant patterns have been reported.
A six-generation family has been reported in which affected members had homozygous mutations in ATOH7 (10q21.3). Based on mouse studies, this gene is expressed in the developing optic cup at the time that coincides with retinal ganglion cell formation. Mice with absence of functioning Atoh7 lack retinal ganglion cells and optic nerves and develop PHPV.
A single family with presumed bilateral PHPV in 3 generations in a pattern consistent with autosomal dominant inheritance has been reported (611308). However, no genotyping was reported and only the proband and his father had ophthalmologic examinations.
Pedigree
Autosomal dominant
Autosomal dominant disorders require only one mutation for the disease to be expressed. Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease. It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).
Autosomal dominant inheritance leads to a vertical pattern of transmission
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.