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Kearns–Sayre syndrome
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
Pigmentary degeneration of the retina may take the pattern of salt and pepper retinopathy in which there are regions of hyper- and hypopigmentation or a bone spicule appearance of retinitis pigmentosa [8]. The Kearns–Sayre triad is ptosis, ophthalmoplegia, and pigmentary retinopathy. There may be optic atrophy. Some patients have had an eventual loss of the pigment epithelium. Others have had a choroideremia pattern in which there is complete choroid atrophy [9]. Supratentorial and cerebellar atrophy have been observed [10].
The eye
Published in Angus Clarke, Alex Murray, Julian Sampson, Harper's Practical Genetic Counselling, 2019
Choroideraemia is a specific X-linked disorder that may be confused with retinitis pigmentosa, especially in its early stages. It is infrequently associated with more generalised, and often severe, developmental problems as part of a contiguous gene deletion syndrome. Norrie disease is the severe end of a spectrum associated with mutation in the NDP gene, which also causes the milder X-linked familial exudative retinopathy. It is associated with progressive deafness and more generalised developmental difficulties in 30%–50% of those affected. Retinoschisis is yet another X-linked disorder, with retinal degeneration associated with a characteristic splitting of the retina, where specific molecular analysis is possible.
How to master MCQs
Published in Chung Nen Chua, Li Wern Voon, Siddhartha Goel, Ophthalmology Fact Fixer, 2017
In choroideremia, ocular albinism and retinitis pigmentosa, pigmentary changes may be observed in the peripheral retina of the female carrier. Retinoschisis and Nome's disease are not associated with abnormal retinal findings in the female carriers.
An optometrist’s guide to the top candidate inherited retinal diseases for gene therapy
Published in Clinical and Experimental Optometry, 2021
Fleur O’Hare, Thomas L Edwards, Monica L Hu, Doron G Hickey, Alexis C Zhang, Jiang-Hui Wang, Zhengyang Liu, Lauren N Ayton
Choroideremia is an X-linked IRD caused by mutations in the CHM gene on the X chromosome, which encodes Rab escort protein-1 (REP1), a protein involved in intracellular transport.48 This condition is an ideal target for gene augmentation therapy as the rate of degeneration is relatively slow, central retinal sensitivity is retained until late stages, and the gene is small enough to be packaged into a carrier viral vector.16 Given its X-linked mode of inheritance, choroideremia principally affects males, with female carriers generally showing milder signs of the disease (as they have a second, normal, copy of the CHM gene on their second X chromosome).49 REP1 deficiency leads to a progressive chorioretinal degeneration that primarily affects the retinal pigment epithelium, with secondary degeneration of the outer retina and choroid.50 Initially retinal thickening occurs, followed by photoreceptor degeneration, RPE depigmentation and finally loss of the RPE and choriocapillaris.51
Progress in the development of novel therapies for choroideremia
Published in Expert Review of Ophthalmology, 2019
Jasmina Cehajic Kapetanovic, Maria I Patrício, Robert E MacLaren
Choroideremia is an X-linked recessive inherited retinal degeneration caused by the loss of function or absence of Rab escort protein 1 (RPE1) which is encoded by the CHM gene [1,2]. There are currently no approved treatments for choroideremia. Gene therapy is a very attractive treatment option for this monogenic eye disorder using an adeno-associated viral vector (AAV), which can easily contain the CHM cDNA cargo of 1.9kB. Proof-of-concept animal [3,4] and in-vitro studies [5–8] have demonstrated efficacy and restoration of REP1 expression, leading to multiple clinical trials [9–16]. This review discusses the progress in pre-clinical research and the development of an in-vitro functional assay that can be used to confirm the diagnosis in challenging cases and to test the vector potency currently used in gene therapy clinical trials [17]. The advances in ongoing clinical trials are also reviewed in view of the recently published reports from the leading centers in choroideremia research [11–14]. Finally, we offer expert opinion on considerations necessary for regulatory approval of gene therapy for choroideremia and discuss the development of alternative therapies including optogenetics for more advanced stages of the disease.
Presence of corneal crystals confirms an unusual presentation of Bietti’s retinal dystrophy
Published in Ophthalmic Genetics, 2019
Won Kyung Song, Penny Clouston, Robert E. MacLaren
With the advent of gene therapy clinical trials, the correct identification of the genetic cause of inherited retinal degenerations has become of paramount importance. Here we report a case of a middle-aged man with a clinical phenotype similar to an advanced choroideremia, but whose father had a clinical picture of a macular dystrophy. The presence of corneal and retinal crystals in both led to the provisional diagnosis of pseudodominantly inherited BCD, which was confirmed by identification of a homozygous mutation in CYP4V2 by segregation analysis. This report highlights that corneal findings may be helpful in confirming the aetiology of missense changes in CYP4V2. Furthermore, a detailed corneal examination should be considered in patients who have an unusual clinical phenotype resembling choroideremia but inconclusive genetic testing.