J Med Genet 1992: 29: 289-290 289 Annotation J Med Genet: first published as 10.1136/jmg.29.5.289 on 1 May 1992. Downloaded from Cone and cone-rod dystrophies The retinal dystrophies are a genetically het- examination is usually normal. Two main erogeneous group of disorders which may be forms are recognised. In complete achroma- seen as an isolated ocular abnormality or may topsia (rod monochromatism) there are no be associated with other systemic disease. In functioning cone photoreceptors in the retina.4 most disorders the underlying disease mechan- Vision is reduced to the level of about 6/60, ism is not known, so that classification is un- there is no true colour perception, and there satisfactory. There is great clinical heterogen- are normal rod but absent cone responses on eity even among dystrophies which share a electroretinography. Inheritance is autosomal common mode of inheritance. At present, dys- recessive but there may be more than one trophies are most usefully classified according form. Incomplete achromatopsia or blue cone to whether they are stationary or progressive monochromatism is an X linked recessive dis- and whether there is predominantly macular order which presents in a similar fashion but or generalised retinal disease. The latter group has a better visual prognosis.58 Colour vision is subdivided on the basis of whether there is testing and electroretinography show evidence involvement of rod or cone photoreceptors or of normal rod and blue cone function but both. Most disease is progressive and even- absent red and green cone responses."' tually involves both types of photoreceptors. Female heterozygotes may show evidence of Patients with predominantly rod disease com- abnormal cone responses on electroretin- plain of difficulties with night vision and in the ography." Nathans et al,7 in a recent study of early stage of the disease will have normal 12 families with this uncommon disorder, visual acuity and colour vision. Cone dysfunc- found a rearrangement of the red and green tion may be suspected if there is photophobia, cone opsin genes or deletion of an adjacent fine nystagmus, reduced visual acuity, and regulatory region in each case. abnormal colour vision. Although in some cases the diagnosis may be made on the basis of a history and clinical examination alone, Progressive cone and cone-rod further tests of rod and cone function are often dystrophies needed. All regional genetic units should have The progressive cone dystrophies usually pre- http://jmg.bmj.com/ access to a specialised electrodiagnostic service sent in adolescence or early adult life with where isolated cone and rod responses can be reduced vision. Photophobia and nystagmus reliably recorded in both adults and young are common findings and, in contrast to achro- children. This is important for diagnosis but matopsia, there is usually evidence of atrophy also for recognition of the carrier status in X of the retinal pigment epithelium in the macu- linked dystrophies. lar area, giving rise to a so called 'bulls eye' appearance. Colour vision is abnormal at an early stage and the defect is usually of the red- on September 24, 2021 by guest. Protected copyright. Stationary cone dystrophies green type. Electroretinography shows absent Cone dystrophies may be conveniently classi- or substantially abnormal cone responses. fied according to their natural history. The Many patients who present with symptoms stationary cone dystrophies include the com- and signs of a cone dystrophy later develop moner colour vision defects in which there is night blindness and abnormalities of the rod abnormal colour vision but normal visual electroretinogram and are then said to have a acuity, and the different forms of achromatop- cone-rod dystrophy. Cone or cone-rod dys- sia where the colour vision defect is accompan- trophy is usually seen in otherwise normal ied by reduced acuity and nystagmus. Colour subjects but has been reported in association vision in man is trichromatic, that is, there are with the Pierre-Marie type of hereditary three classes of cone photoreceptors that con- ataxia 2 and amelogenesis imperfecta.13 tain visual pigment, maximally sensitive at There are clearly many different disorders 560 nm (red cones), 535 nm (green cones), and with cone dysfunction.'4 15 Some represent 440 nm (blue cones). The genes for the protein pure cone dystrophies but in others, perhaps component (opsin) of the red and green cone the majority, there is later evidence of rod pigments have been localised to adjacent re- dysfunction. At present there is insufficient gions of the long arm of the X chromosome evidence to classify these diseases other than and the blue cone opsin to chromosome 7. 2 by their mode of inheritance. This may be About 8% of men and about 0 5% of women autosomal recessive,6 17 autosomal domin- have a defect in the red-green system and these ant,'4 1821 or X linked recessive,22-24 but there is colour vision defects are associated with ab- clinical heterogeneity within these subtypes. normalities of the red and green opsin genes. 1-3 Many cases are sporadic but in patients with a Achromatopsia presents in infancy with poor family history autosomal dominant inheritance vision, photophobia, and nystagmus. Fundus is most common. 290 Moore 2 Nathans J, Piantanida TP, Eddy RL, Shows TB, Hogness Specialised electrophysiological'6 and psy- DS. Molecular genetics of inherited variation in human chophysical'7 21 24 tests of rod and cone function colour vision. Science 1986;232:203-10. may help identify specific patterns of disease. 3 Nathans J. The genes for colour vision. Sci Am 1989;260:42-9. Went et al in this issue describe a family with a 4 Sharpe LT, van Norrend D, Nordby K. Pigment regenera- dominant progressive cone dystrophy with tion, visual adaptation and spectral sensitivity in the J Med Genet: first published as 10.1136/jmg.29.5.289 on 1 May 1992. Downloaded from achromat. Clin Vis Sci 1988;3:9-17. early loss of blue cone function and a similar 5 Spivey B. The X linked inheritance of atypical mono- family has been described by Bresnick et al.2' chromatism. Arch Ophthalmol 1965;74:327-33. No mutation of the blue cone opsin gene has 6 Weiss AH, Biersdorf WR. Blue cone monochromatism. J7 Pediatr Ophthalmol 1 989;26:2 18-23. been found to date. However, Reichel et aP4 7 Nathans J, Davenport CM, Maumenee IH, et al. Molecular have described an X linked cone dystrophy in genetics of blue cone monochromacy. Science 1989;245:831-8. which there is early loss of red cone function 8 Alpern M, Lee GB, Spivey B. it 1 cone monochromatism. and a deletion of the red cone opsin gene. Arch Ophthalmol 1965;74:334-7. 9 Berson EL, Sandberg MA, Rosner B, Sullivan PL. Color Similar techniques may be useful in X plates to help identify patients with blue cone mono- linked cone dystrophy in defining the status of chromatism. Am J Ophthalmol 1983;95:741-7. females at risk of inheriting the abnormal 10 Hess RF, Mullen KT, Sharpe LT, Zrenner E. The photo- receptors in incomplete achromatopsia. Physiol 23 2 _7 gene. 24 Female heterozygotes are usually 1989;417: 123-49. asymptomatic and in most cases have a normal 11 Berson EL, Sandberg MA, Maguire A, et al. Electroretino- grams of carriers of blue cone monochromatism. AmJ ocular examination. In this issue van Everd- Ophthalmol 1986;102:254-61. ingen et al report the results of colour vision 12 Bjork A, Lindbau U, Wadensten L. Retinal degenerations in hereditary ataxia. Neurol Neurosurg Psychiatry testing using the Nagel anomaloscope and 1956;19: 186-93. foveal densitometry (which measures the cone 13 Jalili IK, Smith NJD. A progressive cone rod dystrophy pigment density) in a group of obligate hetero- and amelogenesis imperfecta: a new syndrome. .7 Med Genet 1988;25:738-40. zygotes. They were able to identify abnormal- 14 Goodman G. Ripps H, Siegel IM. Cone dysfunction syn- ities in 87%, but these tests remain research dromes. Arch Ophthalmol 1963;70:214-31. 15 Weleber RG, Eisner A. Cone degeneration ("bulls eye techniques that are not routinely available dystrophies") and colour vision defects. In: Newsome even in regional ophthalmology units. Accur- DA, ed. Retinal dystrophies and degenerations. New York: ate genetic counselling will have to await the Raven Press, 1988;233-56. 16 Gouras P, Eggars HM, MacKay CJ. Cone dystrophy, localisation of the abnormal genes. nyctalopia and supernormal rod responses. A new retinal Although patients may be helped sympto- degeneration. Arch Ophthalmol 1983;101:718-24. 17 Yagasaki Y, Jacobson SG. Cone-rod dystrophy. Phenotypic matically by the use of tinted lenses, miotics, diversity by retinal function testing. Arch Ophthalmol and low vision aids there is no proven treatment 1989;107:701-8. 18 Berson EL, Gouras PG, Gunkel RD. Progressive cone of the underlying retinal disease. The dis- degeneration, dominantly inherited. Arch Ophthalmol covery of mutations of the cone opsin genes in 1968;80:77-83. some forms of cone dystrophy724 and the 19 Krill AE, Deutmann AF. Dominant macular degenerations. The cone dystrophies. AmJ Ophthalmol 1972;73:352-69. more recent identification of mutations of the 20 Pearlman JT, Owen GW, Brounley DW, Sheppard JJ. rod opsin gene2526 and the peripherin-RDS Cone dystrophy with dominant inheritance. AmJ7 Oph- gene2728 thalmol 1974;77:293-303. in retinitis pigmentosa make it likely 21 Bresnick GH, Smith VC, Pokorny J. Autosomal domin- that other genes coding for proteins involved antly inherited macular dystrophy with preferential short in cone structure wavelength sensitive cone involvement. Am J Ophthalmol http://jmg.bmj.com/ rod and and function will be 1989;108:265-76.