Syndromic retinitis pigmentosa.

Marion M Brands, Arthur A Bergen, Mary J van Schooneveld, Nicoline E Schalij-Delfos, Bart P Leroy, Camiel J F Boon, Clara D M van Karnebeek, Ronald J A Wanders, Carel B Hoyng, Jessica S Karuntu, Hind Almushattat, Xuan-Thanh-An Nguyen, Astrid S Plomp, Maria M van Genderen

Journal: Progress in retinal and eye research 2025;107():101324

PMID: 39733931

Free Full Text on Elsevier Science View on PubMed

Abstract

Retinitis pigmentosa (RP) is a progressive inherited retinal dystrophy, characterized by the degeneration of photoreceptors, presenting as a rod-cone dystrophy. Approximately 20-30% of patients with RP also exhibit extra-ocular manifestations in the context of a syndrome. This manuscript discusses the broad spectrum of syndromes associated with RP, pathogenic mechanisms, clinical manifestations, differential diagnoses, clinical management approaches, and future perspectives. Given the diverse clinical and genetic landscape of syndromic RP, the diagnosis may be challenging. However, an accurate and timely diagnosis is essential for optimal clinical management, prognostication, and potential treatment. Broadly, the syndromes associated with RP can be categorized into ciliopathies, inherited metabolic disorders, mitochondrial disorders, and miscellaneous syndromes. Among the ciliopathies associated with RP, Usher syndrome and Bardet-Biedl syndrome are the most well-known. Less common ciliopathies include Cohen syndrome, Joubert syndrome, cranioectodermal dysplasia, asphyxiating thoracic dystrophy, Mainzer-Saldino syndrome, and RHYNS syndrome. Several inherited metabolic disorders can present with RP, including Zellweger spectrum disorders, adult Refsum disease, α-methylacyl-CoA racemase deficiency, certain mucopolysaccharidoses, ataxia with vitamin E deficiency, abetalipoproteinemia, several neuronal ceroid lipofuscinoses, mevalonic aciduria, PKAN/HARP syndrome, PHARC syndrome, and methylmalonic acidaemia with homocystinuria type cobalamin (cbl) C disease. Due to the mitochondria's essential role in supplying continuous energy to the retina, disruption of mitochondrial function can lead to RP, as seen in Kearns-Sayre syndrome, NARP syndrome, primary coenzyme Q10 deficiency, SSBP1-associated disease, and long chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Lastly, Cockayne syndrome and PERCHING syndrome can present with RP, but they do not fit the abovementioned hierarchy and are thus categorized as miscellaneous. Several first-in-human clinical trials are underway or in preparation for some of these syndromic forms of RP.

Address: Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands.; Department of Ophthalmology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.; Department of Human Genetics, Amsterdam Reproduction & Development, Amsterdam UMC, University of Amsterdam, the Netherlands.; Department of Pediatric Nephrology, Emma Children's Hospital, Amsterdam, the Netherlands; Department of Laboratory Medicine, Laboratory Genetic Metabolic Diseases, Amsterdam UMC, Amsterdam, the Netherlands.; Department of Ophthalmology, Radboud University Medical Center, Nijmegen, the Netherlands.; Bartiméus Diagnostic Center for Complex Visual Disorders, Zeist, the Netherlands; Department of Ophthalmology, University Medical Center Utrecht, Utrecht, the Netherlands.; Department of Pediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.; Department of Ophthalmology, Ghent University Hospital, Ghent, Belgium; Department of Head & Skin, Ghent University, Ghent, Belgium; Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium; Division of Ophthalmology and Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.; Department of Pediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Emma Center for Personalized Medicine, Amsterdam UMC, Amsterdam, the Netherlands.; Emma Center for Personalized Medicine, Amsterdam UMC, Amsterdam, the Netherlands; Department of Ophthalmology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands; Department of Human Genetics, Section Ophthalmogenetics, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.; Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands; Department of Ophthalmology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands. Electronic address: [email protected].

DOI: 10.1016/j.preteyeres.2024.101324

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MeSH Terms: Humans, Retinitis Pigmentosa, Syndrome, Ciliopathies