Elsevier

Survey of Ophthalmology

Volume 51, Issue 3, May–June 2006, Pages 232-258
Survey of Ophthalmology

Current Research
Progressive Cone and Cone-Rod Dystrophies: Phenotypes and Underlying Molecular Genetic Basis

https://doi.org/10.1016/j.survophthal.2006.02.007Get rights and content

Abstract

The cone and cone–rod dystrophies form part of a heterogeneous group of retinal disorders that are an important cause of visual impairment in children and adults. There have been considerable advances made in recent years in our understanding of the pathogenesis of these retinal dystrophies, with many of the chromosomal loci and causative genes having now been identified. Mutations in 12 genes, including GUCA1A, peripherin/RDS, ABCA4 and RPGR, have been described to date; and in many cases detailed functional assessment of the effects of the encoded mutant proteins has been undertaken. This improved knowledge of disease mechanisms has raised the possibility of future treatments for these disorders, for which there are no specific therapies available at the present time.

Section snippets

Photoreception

Cone and rod photoreceptors differ in their photopigment content, physiology, spatial arrangement, and morphology. Rods have long, thin, cylindrical outer segments, whereas cones have shorter conical outer segments. The rod outer segment contains a stack of discs, formed from invaginations of the cell's plasma membrane, and it is within these discs that rod photopigment composed of rod opsin plus chromophore is located. There is a constant process of disc renewal that takes place, with the

The Cone Dysfunction Syndromes

The stationary cone disorders are better described as cone dysfunction syndromes, with the term dystrophy being reserved for progressive inherited conditions. These different syndromes encompass a wide range of clinical, electrophysiological, and psychophysical findings.116 The stationary cone dysfunction syndromes are congenital and have normal rod function; whereas in progressive cone dystrophies, symptoms usually start in childhood or early adult life and most patients usually develop rod

Progressive Cone and Cone–Rod Dystrophies

The inherited cone dystrophies are a heterogeneous group of disorders, with autosomal recessive, autosomal dominant, and X-linked recessive inheritance all having been reported. The functional deficit is confined to the photopic system in some forms of cone dystrophy but in others, perhaps the majority, there is later evidence of rod dysfunction (cone–rod dystrophy).

In this review cone–rod dystrophy (CORD) will be used to describe those retinal disorders in which subjects have significant

Management of Progressive Cone and Cone–Rod Dystrophies

There is currently no specific treatment for any of the progressive cone and cone–rod dystrophies. Nevertheless, it is important that the correct diagnosis is made at an early stage, in order to be able to provide accurate information on prognosis and to be able to offer informed genetic counseling. Molecular genetic diagnosis often facilitates genetic counseling and advice on prognosis; for example, the identification of mutations in GUCY2D or CRX would predict severe visual impairment, and

Conclusion and Future Persepctives

The cone and cone–rod dystrophies form part of a heterogeneous group of retinal disorders that are a major cause of blindness in children and young adults. The purpose of this review has been to describe in detail the phenotypes of several of these progressive dystrophies and their underlying molecular genetic basis. It is hoped that a better understanding of the characteristics, natural history, and disease mechanisms of these conditions will result in improved advice on prognosis and genetic

Method of Literature Search

The authors undertook a MEDLINE search (1966–2005) of articles using the following key words: cone dystrophy, cone–rod dystrophy, cone disorders, cone dystrophy genetics, cone–rod dystrophy genetics, cone dystrophy phenotype, cone–rod dystrophy phenotype. The search was restricted to publications in English or with English abstracts. Inclusion or exclusion of the articles was based on relevance to the subject and the need to avoid redundancy.

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    This work was supported by a grant from the Guide Dogs for the Blind Association and the Wellcome Trust (065454/Z/01/Z). The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this article.

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