Retinitis Pigmentosa
Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal dystrophies characterized by progressive degeneration of photoreceptor cells, primarily rods followed by cones, leading to visual impairment and eventual blindness. The pathogenesis of RP involves mutations in genes crucial for photoreceptor structure and function, resulting in apoptosis of these cells and subsequent loss of retinal pigment epithelium integrity. This degeneration manifests clinically as night blindness, constricted visual fields, and, in advanced stages, central vision loss. The health impacts of RP are profound, encompassing significant morbidity due to visual disability, psychosocial burden, and reduced quality of life. The disease typically presents in childhood or adolescence, though onset and progression can vary widely depending on the genetic subtype. Over time, affected individuals may experience severe limitations in daily activities and independence, necessitating comprehensive medical, rehabilitative, and social support.
This form of RP is inherited in an autosomal dominant manner, meaning only one mutated allele is sufficient to cause the disease. adRP typically presents with a milder and more slowly progressive course compared to other forms. Patients often retain useful vision into middle age. Mutations in genes such as RHO, PRPH2, and RP1 are commonly implicated. Family history is usually positive for similar visual symptoms across successive generations.
arRP requires biallelic pathogenic variants, with both parents typically being asymptomatic carriers. This form often presents earlier in life and progresses more rapidly than the dominant form. Mutations in genes such as USH2A, PDE6A, and CRB1 are frequently observed. The absence of a family history of RP is common, except in the context of consanguinity.
This type is inherited via mutations on the X chromosome, predominantly affecting males, while female carriers may have mild or subclinical features. xlRP is often associated with an earlier onset and a more aggressive progression, frequently leading to significant vision loss by the third or fourth decade of life. The RPGR and RP2 genes are the most commonly implicated.
In this category, RP occurs as part of a broader syndrome with extraocular manifestations. The most notable example is Usher syndrome, which combines RP with sensorineural hearing loss. Bardet-Biedl syndrome and Refsum disease are other syndromic forms, presenting with a constellation of systemic features such as obesity, polydactyly, renal anomalies, and neurological deficits.
This encompasses all forms of RP that are limited to the retina without systemic involvement. Non-syndromic RP can be inherited in autosomal dominant, autosomal recessive, or X-linked patterns, and its clinical course is determined by the specific genetic defect.
Retinitis pigmentosa is the most common group of inherited retinal degenerations, with a global prevalence estimated at approximately 1 in 3,000 to 1 in 5,000 individuals. The disease affects all ethnicities and both sexes, though X-linked forms are more prevalent in males. RP accounts for up to 20% of cases of legal blindness in working-age adults in developed countries. The age of onset varies, but most patients develop symptoms before the age of 20. The prevalence of syndromic forms, such as Usher syndrome, is lower, with Usher syndrome accounting for about 10% of all RP cases. Family history is present in roughly 50–60% of cases, reflecting the high genetic heterogeneity of the disease. Advances in genetic testing have led to the identification of over 80 causative genes, though a significant proportion of cases still lack a molecular diagnosis.
The diagnosis of retinitis pigmentosa is established through a combination of clinical evaluation, functional testing, and genetic analysis. Initial assessment includes a detailed patient and family history, focusing on the onset and progression of night blindness, peripheral visual field loss, and any associated systemic symptoms. Funduscopic examination typically reveals characteristic findings such as bone spicule pigmentation, attenuation of retinal vessels, and optic disc pallor. Functional testing is performed using electroretinography (ERG), which demonstrates reduced or extinguished rod and cone responses, confirming photoreceptor dysfunction. Visual field testing, such as Goldmann or Humphrey perimetry, documents the extent of peripheral vision loss. Optical coherence tomography (OCT) provides high-resolution imaging of retinal layers, revealing thinning and loss of the outer retina. Genetic testing, including targeted gene panels or whole exome sequencing, is increasingly utilized to identify pathogenic variants and establish the inheritance pattern. Additional investigations may include audiometry and systemic evaluation for syndromic forms. Diagnostic criteria are based on typical clinical features, supportive electrophysiological and imaging findings, and confirmation of a disease-causing genetic mutation where possible.
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