North Carolina macular dystrophy (NCMD, MCDR1) is a congenital autosomal dominant trait that appears to be completely penetrant. It is generally nonprogressive except for the development of choroidal neovascular membranes in some patients. The ophthalmoscopic findings are highly ... North Carolina macular dystrophy (NCMD, MCDR1) is a congenital autosomal dominant trait that appears to be completely penetrant. It is generally nonprogressive except for the development of choroidal neovascular membranes in some patients. The ophthalmoscopic findings are highly variable and are always much more dramatic than one would predict from the relatively good visual acuity level, which ranges from 20/20 to 20/400 (median, 20/60). Patients may have only a few drusen in the central macular region (grade I), confluent drusen confined to the central macular region (grade II), or a severe macular coloboma/staphyloma (grade III) involving 3 to 4 disc areas of the central macular region. Color vision is normal. Electrophysiologic studies are also normal (summary by Small, 1998). - Genetic Heterogeneity of Retinal Macular Dystrophy Retinal Macular Dystrophy-1 (MDCR1), also known as North Carolina macular dystrophy (NCMD) has been mapped to chromosome 6q13-q21. MCDR2 (608051) is caused by mutation in the PROM1 gene (604365) on chromosome 4p15, and MCDR3 (608850) has been mapped to chromosome 5p15-p13. See MAPPING for possible additional loci for MCDR.
Lefler et al. (1971) described a family from North Carolina in which members of 4 generations were affected with what the authors termed 'dominant macular degeneration and amino aciduria.' Onset was late in the first decade of life. ... Lefler et al. (1971) described a family from North Carolina in which members of 4 generations were affected with what the authors termed 'dominant macular degeneration and amino aciduria.' Onset was late in the first decade of life. Color vision remained intact, thus distinguishing the disorder, in the opinion of the authors, from Stargardt disease (see 248200). A random urine of 11 of 17 affected family members showed generalized amino aciduria and increased glycine in 2. It was not made clear whether members without macular dystrophy had amino aciduria. The authors thought the abnormality was different from other reported forms of macular dystrophy. Frank et al. (1974) reported further on this North Carolina kindred and described their disorder as progressive foveal dystrophy. According to them, onset was under 1 year of age and the final stage was reached by the early teens at the latest. The fundus lesions consisted of pigmentary changes and drusen limited to the macula. Advanced foveal changes were always evident before a decrease in visual acuity took place. The amino aciduria was unrelated to the macular degeneration. The disorder is probably distinct from the dominant progressive foveal dystrophy described by Deutman (1971) in which onset and attainment of end stage are later, drusen are not seen, and decrease in visual acuity often precedes visible changes in the macula. The disorder is also distinct from dominant drusen of Bruch membrane (126700). Klein and Bresnick (1982) reported a mother and 3 children. From studies of 22 affected members of the Lefler-Frank kindred with what was called North Carolina macular dystrophy by Gass (1987), Small (1989) concluded that the disorder shows little or no progression and that peripheral retinal drusen are variably present, in contrast to the original description of 'normal peripheral retina.' Small (1989) confirmed that Gass's patients were from the Lefler-Frank kindred. Both Gass (1987) and Small (1989) described some severe macular lesions which were staphylomatous or evacuated in appearance, not flat and atrophic as previously described. Visual acuity was much better than anticipated from the ophthalmoscopic appearance. The worst visual acuity was 20/200; the median was 20/40 to 20/50, and many mildly affected persons were completely asymptomatic with 20/20 vision. Small (1989) extended his examinations to many other members of the kindred with discovery of 68 affected persons. Progression occurred in only 2. Small et al. (1991) described a previously unreported branch of the North Carolina macular dystrophy family, adding another 17 affected members to the kindred. One of the 17 experienced a severe episode of deterioration of central vision with the development of a disciform lesion in the macula. The quality of the photographs in this publication was superior to that in earlier publications. Fetkenhour et al. (1976) and Hermsen and Judisch (1984) had described families with what they considered to be distinct disorders, naming them 'central areolar pigment epithelial dystrophy (CAPED)' and 'central pigment epithelial and choroidal degeneration,' respectively. Small et al. (1992) found definitive genealogic connections of these families with the kindred reported by Lefler et al. (1971) and Frank et al. (1974). All were shown to be descendants of 3 Irish brothers in North Carolina. This finding demonstrated that choroidal neovascular membranes may occasionally develop in NCMD. Small et al. (1992) stated that although the condition is named for the geographic region in which founder effect was observed, unrelated families with this disorder had been identified in Texas, Wisconsin, Canada, England, France, Spain, Belize, and Mexico. Voo et al. (2001) presented the clinical course and ocular histopathology of a woman with the same chromosome 6q16 haplotype as the original MCDR1 family. Light microscopy demonstrated a discrete macular lesion characterized by focal absence of photoreceptors and retinal pigment epithelium with attenuation of the Bruch membrane and focal atrophy of the choriocapillaris. Adjacent to the macular lesion, some lipofuscin was identified in the retinal pigment epithelium, corroborating previous reports of drusen surrounding the macular lesion. Rabb et al. (1998) reported an autosomal dominant macular dystrophy in a family of Mayan Indian descent. The phenotype was clinically indistinguishable from NCMD. Multipoint linkage analysis generated a peak lod score of 5.6 in the MCDR1 region after genotyping 26 individuals of the 56-member family. The haplotype associated with the disease was different from that of the North Carolina family, suggesting that the mutations in MCDR1 occurred independently. Kiernan et al. (2011) reported a 2-stage 30-year follow-up of an African American family with MCDR1, the first from 1970 to 1982 in 10 patients (Leveille et al., 1982) and the second from 2005 to 2009 in 11 patients. Nine of 11 living family members had classic findings ranging from disease grade 2 (confluent foveal drusen, 8 eyes) to grade 3 (central coloboma-like lesion, 10 eyes). Two members developed choroidal neovascularization (CNV), requiring laser ablation, and 1 member developed nonclearing vitreous hemorrhage and underwent 25-gauge pars plana vitrectomy. Another family member developed exotropia and amblyopia in 1 eye by age 7 years. Those without CNV had no significant change in visual acuity over 30 years. Microperimetry analysis of the affected members with grade 3 MCDR1 revealed absent function in the region of the central coloboma-like lesions, corresponding to photoreceptor absence on optical coherence tomography (OCT), although there was preserved foveal function and intact photoreceptors adjacent to the lesion. Kiernan et al. (2011) suggested that eccentric viewing around impaired photoreceptors might explain good acuity in patients with clinical, severe-appearing macular lesions.
In patients from 6q-linked multigenerational families diagnosed with PBCRA (600790) and MCDR1, or in a single patient from an autosomal dominant STGD family, Gehrig et al. (1998) found no disease-associated mutations in the IMPG1 gene (602870).