Clinical features and a follow‐up study in a family with X‐linked progressive cone‐rod dystrophy

Abstract

ABSTRACT.Purpose: To study a large family with X-linked progressive cone-rod dystrophy. Methods: There were 128 members in the family. Of these, 45 had an ophthalmological examination and 3 gave their permission to use the results of their recent ophthalmological examination. In addition to the usual eye examination, visual fields, colour vision, dark adaptation and electroretinogram (ERG) were examined. Results: Ten affected men aged 6 to 81 years were found in the family. The visual acuities varied from counting fingers (cf) 10 cm to 0.5 in the right eye (RE) and from cf 30 cm to 0.4 in the left eye (LE). The refraction was myopic in all affected members, varying from ª1.5 to ª24.0 D (RE) and from ª2.0 to ª20.25 D (LE). In visual functions, central scotomas and concentric constriction in the visual fields, red or red-green defects in colour vision, abnormal cone and rod dark adaptation and affected cone response in ERG were found. The 6 obligate carriers were aged 17 to 77 years. Their visual acuities varied from 0.05 (strabismic amblyopia) to 1.25(RE) and from 0.7 to 1.25 (LE), and refraction from ∫0 to π6.0 D (RE) and from ª0.5 to π5.0 D (LE). Their visual fields and colour vision were normal. The non-affected men were aged 13 to 55 years, their visual acuity was normal in both eyes, and refraction varied from ª5.0 to π1.5 D (RE) and from ª5.5 to π1.75 (LE). The result of the eye examination was normal except in colour vision: two men were congenitally deuteranomalous. The women who were not obligate carriers were aged 10 to 77 years, their visual acuity was from 0.3 to 1.6 in both eyes, and refraction from ª5.5 to π4.75 (RE) and from ª5.25 to π4.0 (LE). Two women had one amblyopic eye. Otherwise the eye examination was normal. Conclusions:The clinical diagnosis of X-linked cone dystrophy 1 (COD1) is based on progressive loss of visual acuity, moderate or high myopia, red colour vision defect and affected cone response or cone and rod response in ERG. The future identification of the COD1 gene will confirm the diagnosis of the disease and help in genetic counseling of the family.

A new genetic locus for X linked progressive cone-rod dystrophy

“…2 However, in this study we could observe two distinct non-recombinant haplotypes (and one recombinant haplotype), in addition to the disease haplotype, in obligate carriers of the second generation, indicating that the disease haplotype was inherited from the father I.1 (fig 1).…”

A new genetic locus for X linked progressive cone-rod dystrophy

“…2 However, in this study we could observe two distinct non-recombinant haplotypes (and one recombinant haplotype), in addition to the disease haplotype, in obligate carriers of the second generation, indicating that the disease haplotype was inherited from the father I.1 (fig 1).…”

Towards Uncovering the Role of Incomplete Penetrance in Maculopathies through Sequencing of 105 Disease-Associated Genes

“…Multifocal ERG (mfERG) showed that the responses were marginally reduced relative to normal. The clinical diagnosis for this patient was inconclusive, which may be in line with a mild phenotype associated with an X-linked carrier phenotype [ 37 , 38 ]. Thus, we consider this patient to be possibly solved.…”

Tilted disc syndrome and colour vision

“…The colour vision defects found in patients with tilted disc syndrome were red, green, blue and mostly mixed defects. All these defects have been reported in both retinal and optic nerve diseases (Pinckers et al 1993;Small & Gehrs 1996;Schneck & Haegesrstrom-Portnoy 1997;Maaranen et al 2000;Ma¨ntyja¨rvi et al 2001;Puomila et al 2005). One theory suggests that tilted disc syndrome is a form of congenital coloboma of the optic nerve caused by malclosure of the embryonic ocular fissure (Riise 1975;Young et al 1976).…”

A new genetic locus for X linked progressive cone-rod dystrophy

“…2 However, in this study we could observe two distinct non-recombinant haplotypes (and one recombinant haplotype), in addition to the disease haplotype, in obligate carriers of the second generation, indicating that the disease haplotype was inherited from the father I.1 (fig 1).…”

Towards Uncovering the Role of Incomplete Penetrance in Maculopathies through Sequencing of 105 Disease-Associated Genes

“…Multifocal ERG (mfERG) showed that the responses were marginally reduced relative to normal. The clinical diagnosis for this patient was inconclusive, which may be in line with a mild phenotype associated with an X-linked carrier phenotype [ 37 , 38 ]. Thus, we consider this patient to be possibly solved.…”

Tilted disc syndrome and colour vision

“…The colour vision defects found in patients with tilted disc syndrome were red, green, blue and mostly mixed defects. All these defects have been reported in both retinal and optic nerve diseases (Pinckers et al 1993;Small & Gehrs 1996;Schneck & Haegesrstrom-Portnoy 1997;Maaranen et al 2000;Ma¨ntyja¨rvi et al 2001;Puomila et al 2005). One theory suggests that tilted disc syndrome is a form of congenital coloboma of the optic nerve caused by malclosure of the embryonic ocular fissure (Riise 1975;Young et al 1976).…”

A new genetic locus for X linked progressive cone-rod dystrophy

“…2 However, in this study we could observe two distinct non-recombinant haplotypes (and one recombinant haplotype), in addition to the disease haplotype, in obligate carriers of the second generation, indicating that the disease haplotype was inherited from the father I.1 (fig 1).…”

Towards Uncovering the Role of Incomplete Penetrance in Maculopathies through Sequencing of 105 Disease-Associated Genes

“…Multifocal ERG (mfERG) showed that the responses were marginally reduced relative to normal. The clinical diagnosis for this patient was inconclusive, which may be in line with a mild phenotype associated with an X-linked carrier phenotype [ 37 , 38 ]. Thus, we consider this patient to be possibly solved.…”

Tilted disc syndrome and colour vision

“…The colour vision defects found in patients with tilted disc syndrome were red, green, blue and mostly mixed defects. All these defects have been reported in both retinal and optic nerve diseases (Pinckers et al 1993;Small & Gehrs 1996;Schneck & Haegesrstrom-Portnoy 1997;Maaranen et al 2000;Ma¨ntyja¨rvi et al 2001;Puomila et al 2005). One theory suggests that tilted disc syndrome is a form of congenital coloboma of the optic nerve caused by malclosure of the embryonic ocular fissure (Riise 1975;Young et al 1976).…”