OMIM ID:
Retinitis Pigmentosa, AR
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
The term retinitis pigmentosa is applied to a large group of disorders with great clinical and genetic heterogeneity. The ocular disease is characterized by night blindness, field constriction, and pigmentary changes in the retina. The latter is sometimes described as having a ‘bone corpuscle’ appearance with a perivascular distribution. A ring scotoma is usually evident. Age of onset and rate of progression is highly variable, even within families. The rods are impacted early but cone deterioration with loss of central vision usually follows. Some patients complain of dyschromatopsia and photophobia. The ERG generally documents this progression but the mfERG shows wide variations in central cone functioning. Legal blindness is common by the 5thdecade of life or later. The course of clinical and ERG changes is more aggressive in the X-linked form than in the autosomal dominant disease. The final common denominator for all types is first rod and then cone photoreceptor loss through apoptosis.
As many as 50% of patients develop posterior subcapsular cataracts. The vitreous often contains cells and particulate debris. Retinal arterioles are often attenuated and the optic nerve may have a waxy pallor, especially late in the disease. Occasional patients have cysts in the macula. Some patients experience continuous photopsia.
Systemic Features
The ‘simple’ or nonsyndromal type of RP described here has no systemic features. However, the retinopathy is seen in a number of syndromes and, of course, in some infectious diseases as well. It is more accurate to label the fundus finding as 'pigmentary retinopathy' in such cases.
Genetics
Inheritance
A significant proportion of RP cases occur sporadically, i.e., without a family history. Mutations in more than 30 genes cause autosomal recessive RP disorders and these account for more than half of all cases of retinitis pigmentosa. More than 100 mutations have been identified in the RHO gene (3q21-q24) alone. Mutations in some genes cause RP in both autosomal recessive and autosomal dominant inheritance patterns. Compound heterozygosity is relatively common in autosomal recessive disease. See OMIM 268000 for a complete listing of mutations.
Many genes associated with retinitis pigmentosa have also been implicated in other pigmentary retinopathies. In addition, numerous phenocopies occur, caused by a variety of drugs, trauma, infections and numerous neurological disorders. To make diagnosis even more difficult, the fundus findings and ERG responses in nonsyndromic RP in most patients are too nonspecific to be useful for classification. Extensive systemic and ocular evaluations are important and should be combined with genotyping in both familial and nonfamilial cases to determine the diagnosis and prognosis.
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.