Retinitis pigmentosa with or without skeletal anomalies is a condition caused by pathogenic variants of the CWC27 gene, characterized by the combination of the progressive vision loss typical of retinitis pigmentosa and various skeletal anomalies, especially short stature and abnormally short fingers and toes or brachydactyly.
Retinitis Pigmentosa with or without Skeletal Abnormalities
The CWC27 gene provides instructions for making a protein that is an essential component of the spliceosome. The spliceosome is a complex molecular machine within our cells that processes messenger RNA (mRNA) in a critical step of gene expression called splicing. The process of splicing plays a fundamental role in generating the protein diversity needed to establish the complex structures and functions found in all eukaryotes. When mutations in both copies of the CWC27 gene alter its function, the efficiency and accuracy of the spliceosome are affected.
This defect in splicing is particularly detrimental to highly specialized cells that depend on the correct expression of many complex genes, such as photoreceptor cells in the retina and developing bone cells (osteoblasts).
The condition is inherited in an autosomal recessive pattern, meaning an individual must inherit a mutated gene from both parents to be affected.
Symptoms
The symptoms are divided into two main categories. Ocular symptoms are those of typical retinitis pigmentosa, with onset of night blindness (nyctalopia) in childhood or adolescence, followed by a gradual but progressive loss of the peripheral visual field. Skeletal abnormalities are also present from an early age and commonly include disproportionate short stature and brachydactyly.
Disease management
There is no cure for this condition; therefore, management focuses on monitoring symptoms and providing supportive care. This involves regular follow-up with an ophthalmologist to monitor the progression of retinitis pigmentosa. An orthopedic evaluation is recommended to manage any significant skeletal issues, such as scoliosis. Genetic counseling is an important resource for affected individuals and their families to understand the inheritance and implications of the disorder.
Genes analyzed
Bibliography
Xu M, Xie YA, Abouzeid H, et al. Mutations in the Spliceosome Component CWC27 Cause Retinal Degeneration with or without Additional Developmental Anomalies. Am J Hum Genet. 2017 Apr 6.100(4):592-604. doi: 10.1016/j.ajhg.2017.02.008.
Yassin SH, Henderson R, Lenberg J, et al. Further delineation of the CWC27-associated spliceosomeopathy: Case report and review of the literature. Am J Med Genet A. 2023 May.191(5):1378-1383.
