Cone Rod Dystrophy
A rare genetic isolated inherited retinal disorder characterized by primary cone degeneration with significant secondary rod involvement, with a variable fundus appearance. Typical presentation includes decreased visual acuity, central scotoma, photophobia, color vision alteration, followed by night blindness and loss of peripheral visual field.
Epidemiology
The prevalence is estimated at 1 in 40,000 in Europe.
Clinical description
Cone rod dystrophy (CRD) is characterized by primary cone involvement or, occasionally, by concomitant loss of both cones and rods, explaining the predominant symptoms of CRDs: decreased visual acuity, color vision defects, photoaversion and decreased sensitivity in the central visual field, later followed by progressive loss in peripheral vision and night blindness. The fundus appearance is varaible ranging from normal in the early stages, with only subtle temporal optic nerve pallor, macular pigment migration and atrophy or a bull's-eye maculopathy, to peripheral retinal pigment epithelium atrophy, intra retinal pigmentation migration, arteriolar attenuation, and optic disc pallor as disease progresses. Cone-rod dystrophy (CRD) should be distinguished from rod-cone dystrophy (RCD), also known as retinitis pigmentosa. Unlike RCD, which typically start with night blindness and progressive visual field constriction while central vision is preserved until late stages, CRD is characterized by a primary decrease in central vision leading to earlier legal blindness. At end stage, however, CRDs do not differ from end stage RCDs. CRDs are most frequently nonsyndromic, however they may also be part of several syndromes, such as Alström syndrome, Bardet-Biedl syndrome and Spinocerebellar Ataxia Type 7.
Etiology
Nonsyndromic CRDs are genetically heterogeneous (28 genes have been identified). The four most commonly mutated genes are ABCA4 (1p22.1) responsible for 30 to 60% of autosomal recessive CRDs, CRX (19q13.33) and GUCY2D (17p13.1) responsible for many reported cases of autosomal dominant CRDs, and RPGR (Xp11.4) responsible for X-linked CRDs.
Diagnostic methods
The diagnosis of CRD is based on clinical history, fundus examination, autofluorescence imaging, optical coherence tomography and full field electroretinogram. Molecular diagnosis can be made for some genes. Fundus examination can be normal at the early stages with only subtle temporal optic disc pallor or may show macular pigment migrations and atrophy or a bull's-eye maculopathy. Late stage findings include peripheral retinal pigment epithelium atrophy, intraretinal pigment migration, arteriolar attenuation, and optic disc pallor.
Differential diagnosis
Differential diagnosis includes other hereditary cone disorders (including achrompatopsia and allied cone dysfunction syndromes, cone dystrophy and Stargardt disease) and the rod-cone dystrophy, also known asretinitis pigmentosa, which is distinguished by the sequence of photoreceptor involvement (rod photoreceptors followed by cone photoreceptors).
Genetic counseling
Inheritance patterns depend on the gene involved and can be autosomal dominant, autosomal recessive or X-linked recessive. Genetic counseling is always advised.
Management and treatment
Currently, there is no therapy that stops evolution of the disease or that restores vision. Management aims at slowing down the degenerative process, treating the complications, visual rehabilitation and helping patients to cope with the social and psychological impact of blindness.
Prognosis
Visual prognosis is variable, with early central vision loss and progressive visual dysfunction leading to legal blindness before 40 years of age in most cases.