Retinitis Pigmentosa & Related Dystrophies

Overview & Clinical Features

Retinitis pigmentosa (RP) is a genetically heterogeneous group of inherited photoreceptor dystrophies that affects rod photoreceptors first. Rods are concentrated in the mid-periphery and drive dark-adapted vision, so the earliest symptom is classically nyctalopia (night blindness). Peripheral visual field constriction follows gradually. Central vision stays intact until late in the disease, when cone function finally begins to fail too.

The fundus exam shows a classic triad. Peripheral bone-spicule pigmentation appears as dark, branching perivascular deposits, formed as RPE cells migrate into the retina while photoreceptors degenerate. Retinal arterioles attenuate as metabolic demand falls with the dying photoreceptors. The optic disc develops a waxy, yellowish pallor, distinct from the paler disc seen in optic atrophy from other causes, reflecting chronic photoreceptor loss and gliosis.

Inheritance Patterns

Nonsyndromic RP can follow nearly any Mendelian pattern. Autosomal recessive inheritance accounts for the largest share of cases, followed by autosomal dominant, then X-linked disease. X-linked RP is the least common of the three but tends to produce the most severe phenotype.

In autosomal dominant RP, mutations in rhodopsin (RHO) are the single most common cause, accounting for roughly a quarter of AD-RP cases. RHO encodes the light-sensing photopigment in rod outer segments. In X-linked RP, mutations in RPGR account for approximately 70% of cases and produce a particularly severe phenotype in affected males.

Visual Field & ERG Findings

Beyond the earliest night-blindness stage, peripheral field loss develops a characteristic pattern. A ring scotoma forms in the mid-periphery and progressively constricts inward and outward, eventually producing tunnel vision as central vision is finally threatened.

Electroretinography reflects the same rod-first logic. The scotopic (dark-adapted, rod-driven) response is diminished or extinguished earlier and more severely than the photopic (cone-driven) response. This finding is key for diagnosis and staging, especially before fundus changes become obvious.

Syndromic RP

Usher Syndrome

Usher syndrome is the most common cause of combined deafness and blindness, pairing sensorineural hearing loss with progressive RP. It is subdivided into types 1, 2, and 3 by the severity and age of onset of both the auditory and retinal components.

Bardet-Biedl Syndrome

Bardet-Biedl syndrome is a ciliopathy, caused by mutations in any of numerous BBS genes that disrupt primary cilium function, a structure photoreceptors depend on heavily. The resulting phenotype combines retinal dystrophy with obesity, polydactyly, and renal anomalies, and shows substantial genetic heterogeneity across the different BBS loci.

Related Inherited Retinal Conditions

Cone-Rod Dystrophy

Cone-rod dystrophy is distinguished from RP by which photoreceptor class fails first: central vision loss, dyschromatopsia, and photophobia appear early, while night vision and the peripheral field stay relatively intact until much later. Electroretinography confirms the pattern, with photopic (cone-driven) amplitudes dropping out of proportion to scotopic (rod-driven) responses. A patient who loses central acuity and color vision before developing night blindness points toward cone-rod dystrophy rather than RP, even before fundus changes appear.

Choroideremia

Choroideremia is an X-linked disorder caused by mutations in CHM, which encodes Rab escort protein 1 (REP1), required for prenylation of the Rab GTPases that drive intracellular trafficking in the RPE and photoreceptors. Loss of this trafficking function leads to progressive degeneration of the choroid, RPE, and photoreceptors. The resulting picture overlaps with RP but with more prominent choroidal involvement.

Gyrate Atrophy

Gyrate atrophy is autosomal recessive and results from deficiency of ornithine aminotransferase (OAT), the enzyme that normally breaks down ornithine. Plasma ornithine accumulates, and the hyperornithinemia drives progressive, well-demarcated scalloped atrophy of the choroid and retina starting in the midperiphery, an appearance that can be mistaken for choroideremia on fundus exam. Night blindness and high myopia present first, usually in adolescence, with central vision lost by the fourth or fifth decade. An arginine-restricted diet combined with pyridoxine (vitamin B6) lowers plasma ornithine and has slowed progression in some reported cases.

X-Linked Juvenile Retinoschisis

X-linked juvenile retinoschisis is caused by mutations in RS1, which encodes retinoschisin, a protein important for maintaining the retina's structural integrity. Loss of function splits the retinal layers themselves (schisis) and produces a classic macular "spoke-wheel" pattern on exam.

Leber Hereditary Optic Neuropathy

Leber hereditary optic neuropathy (LHON) is included here as a related hereditary condition, despite being primarily an optic neuropathy rather than a retinal dystrophy. It results from point mutations in mitochondrial DNA and is transmitted maternally, since mitochondria are inherited almost exclusively from the mother. That inheritance pattern is sharply different from the nuclear-gene Mendelian patterns governing RP and its relatives above.

High-Yield Pearls

• Deafness + RP = Usher syndrome; obesity + polydactyly + renal anomalies + RP = Bardet-Biedl (a ciliopathy).
• Choroideremia (CHM/REP1) and XLRS (RS1) are both X-linked but are mechanistically distinct from RPGR-related X-linked RP.
• LHON's maternal, mitochondrial inheritance pattern is a common distractor gene/inheritance-matching item.

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