Retinitis pigmentosa (RP) refers to a heterogeneous group of inherited ocular diseases that result in a progressive retinal degeneration affecting 1 in 3,000 to 5,000 people (Veltel et al., 2008). Symptoms include night blindness, the development of tunnel ... Retinitis pigmentosa (RP) refers to a heterogeneous group of inherited ocular diseases that result in a progressive retinal degeneration affecting 1 in 3,000 to 5,000 people (Veltel et al., 2008). Symptoms include night blindness, the development of tunnel vision, and slowly progressive decreased central vision starting at approximately 20 years of age. Upon examination, patients have decreased visual acuity, constricted visual fields, dyschromatopsia (tritanopic; see 190900), and the classic fundus appearance with dark pigmentary clumps in the midperiphery and perivenous areas ('bone spicules'), attenuated retinal vessels, cystoid macular edema, fine pigmented vitreous cells, and waxy optic disc pallor. RP is associated with posterior subcapsular cataracts in 39 to 72% of patients, high myopia, astigmatism, keratoconus, and mild hearing loss in 30% of patients (excluding patients with Usher syndrome; see 276900). Fifty percent of female carriers of X-linked RP have a golden reflex in the posterior pole (summary by Kaiser et al., 2004). - Juvenile Retinitis Pigmentosa Autosomal recessive childhood-onset severe retinal dystrophy is a heterogeneous group of disorders affecting rod and cone photoreceptors simultaneously. The most severe cases are termed Leber congenital amaurosis (see 204000), whereas the less aggressive forms are usually considered juvenile retinitis pigmentosa (Gu et al., 1997). Autosomal recessive forms of juvenile retinitis pigmentosa can be caused by mutation in the SPATA7 (609868), LRAT (604863), and TULP1 (602280) genes (see LCA3, 604232, LCA14, 613341, and LCA15, 613843, respectively). An autosomal dominant form of juvenile retinitis pigmentosa (see 604393) is caused by mutation in the AIPL1 gene (604392).
Retinitis pigmentosa is characterized by constriction of the visual fields, night blindness, and fundus changes, including 'bone corpuscle' lumps of pigment. Many cases in successive generations have been reported, e.g., Ayres (1886) 4 generations, Bordley (1908) 5 generations, ... Retinitis pigmentosa is characterized by constriction of the visual fields, night blindness, and fundus changes, including 'bone corpuscle' lumps of pigment. Many cases in successive generations have been reported, e.g., Ayres (1886) 4 generations, Bordley (1908) 5 generations, Allan and Herndon (1944) 5 generations, Heuscher-Isler et al. (1949) 11 cases in 3 generations, and Rehsteiner (1949) 16 cases in 4 generations. The most extensively affected family reported is probably that studied by Beckershaus (1925). Sunga and Sloan (1967), who described a family with 13 affected in 3 generations, including 2 instances of male-to-male transmission, remarked on the wide variability in the rate of visual deterioration among individuals of the same family. The pathophysiology of retinitis pigmentosa was discussed by Dowling (1966), who presented experiments suggesting that exposure to bright light may accelerate the degenerative process. In a survey of retinitis pigmentosa in 5 Swiss cantons, Ammann et al. (1961) found congenital deafness associated in 16 of 118 living cases (see 276900). Kaplan et al. (1990) reviewed 93 cases of retinitis pigmentosa. Sporadic cases represented the major category (42%). In this group, at least 3 clinical forms could be recognized: cone-rod dystrophy, early-onset severe forms, and late-onset moderate forms. At the beginning of the disease, the hereditary nature of the sporadic forms was difficult to ascertain, especially between 7 and 10 years of age, and only the clinical course could possibly provide information regarding the mode of inheritance. A high level of consanguinity and a preponderance of males in the early-onset, severe sporadic forms (including cone-rod dystrophy) suggested autosomal or X-linked recessive inheritance, while increased paternal age in late-onset forms was suggestive of autosomal dominant mutations. Ben-Arie-Weintrob et al. (2005) reviewed the published histopathologic findings of patients with retinitis pigmentosa or an allied disease in whom the responsible gene defect had been identified. Janaky et al. (2007) analyzed multifocal electroretinograms (mfERGs) in patients with RP with various forms of inheritance and duration of disease, with constricted visual fields and visual acuity satisfactory for steady fixation. Their results suggested highly variable central responses and groups of cones with preserved function in areas previously considered nonresponsive. The authors noted that the high variability of the central responses could have been the result of variable foveal cone density, with differences in inheritance- and duration-related cone degeneration at the time of examination. Janaky et al. (2007) stressed the value of step-by-step analysis of the trace array of the mfERGs, which could reveal the groups of cones that were still functioning. Macrae (1982) tabulated the percentage frequency of the 3 mendelian forms of retinitis pigmentosa, as observed in 5 studies including his own in Ontario. Autosomal dominants varied from 9% (in Switzerland) to 39% (in the U.K.); autosomal recessives from 90% (in Switzerland) to 15% (in the U.K.) and X-linked from 1% (in Switzerland and Russia) to 15% (in the U.K.). In the City of Birmingham, England, Bundey and Crews (1984) found a prevalence of retinitis pigmentosa for all ages of 1 in about 5,000. By clinical, electrophysiologic, and psychophysical criteria, Fishman et al. (1985) discerned 4 types of autosomal dominant RP among 84 patients. Type 1 showed diffuse fundus pigmentary changes and nondetectable cone and rod functions by electroretinogram (ERG). Types 2 and 3 showed more apparent pigmentary changes in the inferior retina. Type 2 showed marked loss of rod ERG function with prolonged cone implicit times, whereas type 3 patients showed substantial rod function and normal cone implicit times. Type 4 had funduscopically and functionally 'delimited' disease. Galbraith et al. (1986) studied 34 patients with RP: 23 sporadic, 3 autosomal dominant, 7 autosomal recessive, and 1 X-linked. Antibodies reactive with heterologous neural tissue were found in 17 of the 34, in 1 of 30 normal controls, and also in disease-free first-degree relatives and spouses of RP patients. The antibodies were specific for high molecular weight protein subunits of neurofilaments. These workers thought that release of piled-up neurofilaments from damaged neurons in RP triggers B lymphocytes autoreactive to neurofilament antigens. In Norway, Grondahl (1987) found retinitis pigmentosa in 101 persons in 53 families. The prognosis for visual function was most favorable for the autosomal dominant group (38 patients from 8 families). The autosomal recessive group (40 patients from 25 families) and the 19 solitary cases were heterogeneous, with prognosis ranging from favorable to very bad. Intrafamilial correlation was higher in the autosomal recessive group than in the autosomal dominant group. The overall prevalence of RP in Norway was 1/4,440, the autosomal dominant form being the most frequent. Atypical RP occurs in a number of other conditions, the Flynn-Aird syndrome (136300) being an autosomal dominant example. A clinically distinct variant referred to as type II ADRP was found to segregate independently of chromosome 3q markers (Inglehearn et al., 1990; Farrar et al., 1990; Blanton et al., 1990, 1991). Field et al. (1982) had presented data that excluded an autosomal dominant RP gene from nearly 40 cM around the transferrin (TF; 190000) locus, at 3q21. In 2 families with late-onset, moderately severe RP, Kaplan et al. (1990) excluded linkage to a marker close to rhodopsin (180380). Massof and Finkelstein (1981) had suggested that autosomal dominant retinitis pigmentosa can be divided into type I (early onset) with night blindness before 10 years, and type II (late onset) beginning in the third decade. These 2 types can be further distinguished on the basis of persistence of a measurable rod electroretinogram (Arden et al., 1983) and also on the distribution of pigmentation in the affected retina in the early stages of the disease (Lyness et al., 1985). Classification on the latter basis gives the diffuse (D) and regional (R) types, which correspond to the early (type I) and late (type II) onset categories of Massof and Finkelstein (1981), respectively. Blanton et al. (1991) commented, however, that there was 'no remarkable clinical disparity in the expression of disease caused by the different loci' identified by linkage studies.
For a discussion of the molecular genetics of particular forms of retinitis pigmentosa, see the pertinent entries, listed in the INHERITANCE section.
Sohocki et al. (2001) screened for mutations in 5 genes in a large number ... For a discussion of the molecular genetics of particular forms of retinitis pigmentosa, see the pertinent entries, listed in the INHERITANCE section. Sohocki et al. (2001) screened for mutations in 5 genes in a large number of individuals with retinitis pigmentosa and other inherited retinopathies. In the retinitis pigmentosa group there were 423 tested individuals, of which 206 had autosomal dominant RP, 138 had isolated/recessive RP, and 79 had RP of unknown nature because of unavailability of family history. Mutations in the rhodopsin gene (180380) were found in 59 of the 423 patients. Nineteen had mutations in the peripherin/RDS gene. Eight had mutations in the RP1 gene (603937). Two had mutations in the CRX gene (602225), and none had mutations in the AIPL1 gene (604392), which has been found to be mutant in cases of Leber optic atrophy and in retinal disorders with cone involvement. Kondo et al. (2004) used an established strategy of flexible, multiplexed, microsatellite-based homozygosity mapping to identify mutations in known candidate genes in 59 patients with autosomal recessive or simplex retinitis pigmentosa. Of the 59 probands examined (12 consanguineous and 47 nonconsanguineous), 24 had a mean of 1.4 genes showing homozygosity for all markers within the corresponding gene region. Subsequent direct sequencing revealed 3 homozygous mutations. Two of them were novel mutations in the genes TULP1 (602280.0006) and CNGB1 (600724.0002). The other was a mutation in the RPE65 gene (180069.0008) that was known to cause Leber congenital amaurosis (204000). The clinical features of each patient, together with the cosegregation analysis, strongly supported the pathogenicity of these mutations. Coppieters et al. (2007) noted RetNet (the Retinal Information Network) as recording 17 autosomal dominant loci, 25 autosomal recessive loci, and 6 X-linked recessive loci causing retinitis pigmentosa. Autosomal dominant retinitis pigmentosa (adRP) represents a genetically heterogeneous group of retinal dystrophies in which 54% of all cases can be attributed to 17 disease loci.