Summary
The clinical course of defective vision and blindness has been investigated in relation to different modes of genetic transmission in a large series of 93 families with retinitis pigmentosa (RP). For autosomal dominant RP, two clinical subtypes could be distinguished according to the delay in macular involvement. In the severe form, macular involvement occurred within 10 years, while in the mild form, macular involvement occurred after 20 years. Interestingly, a significant increase of mean paternal age (38.8 years, mean controls in France = 29.1 years, P < 0.001) was found in this form of RP, a feature which is suggestive of new mutations. For autosomal recessive RP, four significantly different clinical subtypes could be recognized, according to both age of onset and the pattern of development (P < 0.001), namely cone-rod dystrophy and early-onset severe forms on the one hand (mean age of onset = 7.6 years), late-onset mild forms and senile forms on the other. Similarly, two significantly different clinical subtypes could be recognized in X-linked RP, according to both mode and age of onset, which were either myopia (mean age = 3.5±0.5 years) or night blindness (mean age = 10.6±4.1 years, P < 0.001). By contrast, no difference was noted regarding the clinical course of the disease, which was remarkably severe whatever the clinical subtype (blindness before 25 years). In addition, all obligate carriers in our series were found to have either severe myopia or pigment deposits in their peripheral retina. Finally, sporadic RP represented the majority of cases in our series (42%). There was a considerable heterogeneity in this group, and at least three clinical forms could be recognized, namely cone-rod dystrophy, early onset-severe forms and late onset moderate forms. At the beginning of the disease, the hereditary nature of the sporadic forms was very difficult to ascertain (especially between 7–10 years) and only the clinical course could possibly provide information regarding the mode of inheritance. However, the high level of consanguinity, and the high sex ratio in early onset and severe sporadic forms (including cone-rod dystrophy), was suggestive of an autosomal or X-linked recessive inheritance, while increased paternal age in late onset forms was suggestive of autosomal dominant mutations.
Similar content being viewed by others
References
Berson EL, Rosner B, Simonof E (1980) Risk factors for genetic typing and detection in retinitis pigmentosa. Am J Ophthalmol 89:763–775
Bhattacharya SS, Wright AF, Clayton JF, Price WH, Phillips CI, McKeown CME, Jay M, Bird AC, Pearson PL, Southern EM, Evans HJ (1984) Close genetic linkage between X-linked retinitis pigmentosa and a restriction fragment length polymorphism identified by a recombinant DNA probe L1–28. Nature 309:253–255
Bhattacharya SS, Clayton JF, Harper PS, Hoare GW, Jay MR, Lyness AL, Wright AF (1985) A genetic linkage study of a kindred with X-linked retinitis pigmentosa. Br J Ophthalmol 69:340–347
Boughman JA, Caldwell RJ (1982) Assessment of clinical variables and counseling needs in patients with retinitis pigmentosa. Am J Med Genet 12:185–193
Boughman JA, Fishman GA (1983) A genetic study of retinitis pigmentosa. Br J Ophthalmol 67:449–454
Boughman JA, Connfally PM, Nance WE (1980) Population genetic studies of retinitis pigmentosa. Am J Hum Genet 32:223–235
Briard ML, Feingold J, Bonaiti-Pellie C, Lapeyre F, Frezal J, Varangot J (1975) Fréquence des malformations à la naissance. Etude d'une maternité parisienne. Arch Fr Pediatr 32:123–128
Bundey S, Crews J (1984) A study of retinitis pigmentosa in the city of Birmingham. I. Prevalence. J Med Genet 21:417–420
Bundey S, Crews J (1984) A study of retinitis pigmentosa in the city of Birmingham. II. Clinical and genetic heterogeneity. J Med Genet 21:421–428
Bunker CH, Berson EL, Bromley WC, Hayes RP, Roderick TH (1984) Prevalence of retinitis pigmentosa in Maine. Am J Ophthalmol 97:357–365
Chen JD, Dickinson P, Gray R, Constable I, Sheffield L, Denton MJ (1989) Non allelic mutations in X-linked retinitis pigmentosa. Clin Genet 35:338–342
Farber MD, Fishman GA, Weiss RA (1985) Autosomal dominant inherited retinitis pigmentosa visual acuity loss by subtype. Arch Ophthalmol 103:524–528
Feingold J, Briard ML, Kaplan J, Bonaiti C, Crouzet J, Demailly ML, Morel J, Delthil S (1976) Fréquence des affections héréditaires dans les instituts de déficients visuels. J Genet Hum 24:85–91
Fishman GA (1978) Retinitis pigmentosa: visual loss. Arch Ophthalmol 96:1185–1188
Fishman GA, Weinberg AG, McMahon TT (1986) X-linked recessive retinitis pigmentosa. Clinical characteristics of carriers. Arch Ophthalmol 104:1329–1335
Fishman GA, Farber MD, Derlack DJ (1988) X-linked retinitis pigmentosa. Profile of clinical findings. Arch Ophthalmol (1988) 106:369–375
Grondahl J (1987) Autosomal recessive inheritance in “senile” retinitis pigmentosa. Acta Ophthalmol 67:231–236
Heckenlively JR, Yoser SL, Friedman LH, Oversier JJ (1988) Clinical findings and common symptoms in retinitis pigmentosa. Am J Ophthalmol 105:504–514
Jay M (1982a) Figures and fantasies: the frequencies of the different genetic forms of retinitis pigmentosa. Birth Defects 18:167–173
Jay M (1982b) On the heredity of retinitis pigmentosa. Br J Ophthalmol 66:405–416
Lyness AL, Ernst W, Quinlan MP, Clover GM, Arden GB, Carter RM, Bird AC, Parker JA (1985) A clinical, psychophysical, and electroretinographic survey of patients with autosomal dominant retinitis pigmentosa. Br J Ophthalmol 69:326–329
Marmor MF, Aguirre G, Arden G, Berson E, Birch DG (1983) Retinitis pigmentosa, a symposium on terminology and methods of examination. Ophthalmology 90:126–131
Massof RW, Finkelstein D (1981) Two forms of autosomal dominant primary retinitis pigmentosa. Doc Ophthalmol 51:289–346
McWilliam P, Farrar GJ, Kenna P, Bradley DG, Humphries MM, Sharp EM, McConnell DJ, Lawler M, Sheils D, Ryan C, Stevens K, Daiger SP, Humphries P (1989) Autosomal dominant retinitis pigmentosa (ADRP): localization of an ADRP gene to the long arm of chromosome 3. Genomics 5:619–622
Pagon RA (1988) Retinitis pigmentosa. Surv Ophthalmol 33:137–177
Penrose LS (1955) Parental age and mutation. Lancet II:312–313
Wirth B, Denton MJ, Chen JD, Neugebauer M, Halliday FB, Van Schoonveld M, Donald J, Bleeker-Wargemakers EM, Pearson PL, Gail A (1988) Two different genes for X-linked retinitis pigmentosa. Genomics 2:263–266
Wright AF, Bhattacharya SS, Jay M, Carothers AD, Bird AC, Jay B, Evans HJ (1989) Heterogeneity in X-linked retinitis pigmentosa. (10th International Workshop on Human Gene Mapping) Cytogenet Cell Genet 51
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kaplan, J., Bonneau, D., Frézal, J. et al. Clinical and genetic heterogeneity in retinitis pigmentosa. Hum Genet 85, 635–642 (1990). https://doi.org/10.1007/BF00193589
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00193589