From the Guidelines
Retinitis pigmentosa is commonly associated with several conditions, including Usher syndrome, Bardet-Biedl syndrome, and Refsum disease, as well as other syndromes such as Kearns-Sayre syndrome, Leber congenital amaurosis, and Alström syndrome, and mevalonate kinase deficiency (MKD) which may also present with hearing loss and require ophthalmologic evaluations as clinically indicated 1.
Conditions Associated with Retinitis Pigmentosa
The associations between retinitis pigmentosa and other conditions occur due to genetic mutations affecting retinal photoreceptors that often impact other body systems, particularly when mitochondrial function or ciliary structures are involved.
- Usher syndrome: combines retinitis pigmentosa with hearing loss
- Bardet-Biedl syndrome: characterized by retinitis pigmentosa, obesity, polydactyly, intellectual disability, and kidney abnormalities
- Refsum disease: features retinitis pigmentosa, peripheral neuropathy, cerebellar ataxia, and elevated phytanic acid levels
- Kearns-Sayre syndrome: progressive external ophthalmoplegia and heart conduction defects
- Leber congenital amaurosis: severe early-onset retinal dystrophy
- Alström syndrome: obesity, diabetes, and hearing loss
- Mevalonate kinase deficiency (MKD): rare MKD-associated manifestations include retinitis pigmentosa and hearing loss 1
Importance of Comprehensive Evaluation
Patients with retinitis pigmentosa should undergo comprehensive evaluation to identify any associated conditions, as early detection can improve management of both ocular and systemic manifestations. This evaluation should include ophthalmologic assessments, as well as screenings for other potential associated conditions, such as hearing loss and systemic diseases. It is also worth noting that retinitis pigmentosa has been associated with disorders related to abnormal retinal function and oculodigital stimulation, including albinism, Bardet-Biedl syndrome, Leber congenital amaurosis, tapetoretinal degeneration, and Kurz syndrome 1. However, the most recent and highest quality study 1 highlights the importance of considering mevalonate kinase deficiency (MKD) in patients with retinitis pigmentosa, particularly those with hearing loss, and emphasizes the need for ophthalmologic evaluations as clinically indicated.
From the Research
Conditions Associated with Retinitis Pigmentosa
- Retinitis pigmentosa (RP) can be associated with various syndromic forms, including Bardet-Biedl syndrome (BBS) and Usher syndrome (USH) 2
- BBS is characterized by retinopathy, obesity, hypogonadism, renal dysfunction, postaxial polydactyly, and mental retardation, while USH is marked by congenital or early-onset sensorineural deafness, RP, and variable degrees of vestibular dysfunction 2
- Other conditions associated with RP include:
- Usher syndrome type IIa, which has a worse visual prognosis than non-syndromic RP 3
- Retinal ciliopathies, such as Leber congenital amaurosis, Senior-Loken syndrome, and Joubert syndrome 4
- Systemic disorders, including Alstrom, Edwards-Sethi, Ellis-van Creveld, Jeune, Meckel-Gruber, Orofaciodigital Type 9, and Gurrieri syndromes 4
Genetic Associations
- USH2A mutations are a common cause of RP, with or without congenital sensorineural hearing impairment 3
- Different variants in individual RP genes can alter the clinical phenotype, making diagnosis challenging 5
- USH2A variants can give rise to non-syndromic and syndromic RP, with distinct retinal phenotypes observed in disease-specific organoids 5
Clinical Characteristics
- Patients with USH2A-associated RP often experience severe visual impairment by age 50 3
- Those with Usher syndrome type IIa tend to have an earlier decline in visual function and a higher cumulative risk of visual impairment than those with non-syndromic RP 3
- Macular atrophy is more common in USH individuals than in RP individuals 5