Retinitis Pigmentosa 1

Clinical Characteristics
Ocular Features: 

Night blindness, the predominant presenting symptom, is often noted in the first decade of life but may not be a significant complaint until the third decade.  Concentric peripheral field loss likewise follows a similar timeline.  ERG responses progressively decrease in amplitude and may become undetectable in the second decade.  The retinal disease progresses relentlessly, albeit slowly, as the result of photoreceptor degeneration and most patients have severe visual handicaps by midlife but there is considerable clinical variation.  The pigmentary retinopathy is typical for classical retinitis pigmentosa with vascular attenuation, perivascular bone-spicule pigment clumping, optic atrophy, and generalized retinal atrophy with relative sparing of the macula early in the disease.  Lens opacities are common in late stages of the disease.

Systemic Features: 

No systemic disease is associated with the ocular disorder caused by mutations in RP1.

Genetics

Multiple heterozygous, homozygous, and compound heterozygous mutations in the RP1 gene (8q12.1), sometimes called the oxygen-regulated photoreceptor protein 1 or ORP1 gene, are responsible for this disorder.  The protein product is active specifically in retinal photoreceptors.  Retinitis pigmentosa 1 is generally considered to be an autosomal dominant disorder and accounts for 5-7% of dominantly inherited RP disease.  However, recent reports suggest that some mutations in RP1 are responsible for familial cases transmitted in an autosomal recessive pattern in which the clinical disease is more severe. 

More than 20 different mutant genes have been associated with autosomal dominant RP but many cases lack a family history suggesting additional genetic heterogeneity remains.  Reduced penetrance and variable expressivity characteristic of genetic disease likely contributes to the clinical heterogeneity as well.  For more about autosomal dominant retinitis pigmentosa, see Retinitis Pigmentosa, AD (180380, 268000).  

Treatment
Treatment Options: 

Photoreceptor transplantation has been tried in a number of patients without improvement in central vision or interruption in the rate of vision loss.  Longer term results are needed.  Resensitizing photoreceptors with halorhodopsin using archaebacterial vectors shows promise in mice.  High doses of vitamin A palmitate slow the rate of vision loss but plasma levels and liver function need to be checked at least annually.  Oral acetazolamide can be helpful in reducing macular edema.

Low vision aids and mobility training can be facilitating for many patients.  Cataract surgery may restore several lines of vision at least temporarily.

Several pharmaceuticals should be avoided, including isotretinoin, sildenafil, and vitamin E.

References
Article Title: 

References

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Audo I, Mohand-Sa?Od S, Dhaenens CM, Germain A, Orhan E, Antonio A, Hamel C, Sahel JA, Bhattacharya SS, Zeitz C. RP1 and autosomal dominant rod-cone dystrophy: novel mutations, a review of published variants, and genotype-phenotype correlation. Hum Mutat. 2012 Jan;33(1):73-80.

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Busskamp V, Duebel J, Balya D, Fradot M, Viney TJ, Siegert S, Groner AC, Cabuy E, Forster V, Seeliger M, Biel M, Humphries P, Paques M, Mohand-Said S, Trono D, Deisseroth K, Sahel JA, Picaud S, Roska B. Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa. Science. 2010 Jul 23;329(5990):413-7.

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Berger AS, Tezel TH, Del Priore LV, Kaplan HJ. Photoreceptor transplantation in retinitis pigmentosa: short-term follow-up. Ophthalmology. 2003 Feb;110(2):383-91.

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