Clinical and immunohistochemical evidence for an X linked retinitis pigmentosa syndrome with recurrent infections and hearing loss in association with an RPGR mutation

Retinitis pigmentosa (RP) is the most common form of hereditary retinal degeneration, affecting approximately 1 in 3500 individuals.1,2 Classical RP is characterised by progressive night blindness and constriction of the peripheral visual fields, ultimately causing deterioration of the central vision in many patients. These symptoms are accompanied by ophthalmoscopically detectable degenerative and pigmentary changes of the retinal tissue and by reductions of the electrical retinal response to flashes of light using an electroretinogram (ERG). ERG abnormalities are typically present before any detectable retinal change becomes visible to clinical examination. RP can be transmitted by all inheritance modes, with X linked recessive RP (XLRP) accounting for 10–20% of genetically identifiable cases and being reportedly among the most severe forms.1,2 To date, two of the genes responsible for XLRP have been cloned: RP2 3 and the retinitis pigmentosa GTPase regulator, RPGR .4,5 RPGR accounts for the majority of XLRP.6,7 RP or RP-like retinopathies can also be part of syndromic conditions—that is, associated with extra-ocular manifestations. The most common are Bardet-Biedl and Usher syndromes.1,8–11 Usher syndrome is characterised by the association of RP with sensorineural hearing loss of variable severity, and has three broad clinical phenotypes, with types I and II being the most common.9,11 Type I is characterised by profound congenital non-progressive hearing loss, marked speech impediment, and vestibular dysfunction. The hearing loss of Usher syndrome type II is typically mild to moderate, limited to high frequencies, non-progressive in nature, associated with speech abnormalities commensurate to the hearing defect, and with normal or minimally abnormal vestibular function. Usher syndrome is inherited as an autosomal recessive trait, although a pseudo-dominant Usher syndrome-like phenotype due to a mutation in the mitochondrial MTTS2 gene has been described.12,13 Some reports have …