Characteristically small round white spots (drusen) involving the posterior pole of the eye, including the areas of the macula and optic disc, appear in early adult life. Progression to form a mosaic pattern which Doyne (1899) aptly termed ... Characteristically small round white spots (drusen) involving the posterior pole of the eye, including the areas of the macula and optic disc, appear in early adult life. Progression to form a mosaic pattern which Doyne (1899) aptly termed 'honeycomb' occurs thereafter. Doyne considered it to represent 'choroiditis.' However, Collins (1913) showed that the changes consisted of swelling in the inner part of Bruch membrane. Failing vision usually developed considerably later than the ophthalmologic change. Robert Walter Doyne (1857-1916) was an ophthalmologist in Oxford, England. Pearce (1967) did an extensive study of 6 kindreds living near Oxford. Some and possibly all may have been descendants from a common ancestor. Dominant inheritance with complete manifestation of the trait in persons surviving beyond early adult life was found. Families living elsewhere than England have been reported (see references given by Pearce, 1968). Hutchinson and Tay (1875) gave one of the first descriptions of the constellation of clinical findings later known as age-related macular degeneration. Three of the 10 patients they described were sisters affected with whitish spots (drusen) in the macula. Doyne (1899) reported a similar disorder in which the abnormal spots were nearly confluent, such that the macula had a 'honeycomb' appearance. Collins (1913) described histopathologic findings indicating that the abnormality in one of Doyne's patients consisted of hyaline thickenings of Bruch membrane. Vogt (1925) published the first description of the ophthalmoscopic appearance of a form of familial drusen that had been observed in patients living in the Leventine valley in the Ticino canton of southern Switzerland. The autosomal dominant inheritance was established. Waardenburg (1948) concluded there was little reason to make a distinction between malattia leventinese and the condition described by Doyne (1899). Forni and Babel (1962) found that the histopathologic features of leventinese disease are indistinguishable from those of Doyne honeycomb choroiditis. Piguet et al. (1995) pointed out that the drusen in families with malattia leventinese are frequently distributed in a radial pattern. Although it is unknown what fraction of late-onset macular degeneration is caused by the gene or genes involved in malattia leventinese or Doyne disease, the clinical and histopathologic features suggest the diagnosis of age-related macular dystrophy. Gregory et al. (1996) noted that Doyne honeycomb retinal dystrophy (DHRD) and malattia leventinese are both characterized by drusen. They cited reports describing the lesions of malattia leventinese as small discrete drusen which radiate into the peripheral retina; later, confluent soft drusen develop at the macula. Histopathologic studies established that the radial deposits are continuous with or internal to the basement membrane of the retinal pigment epithelium. In DRHD, large soft drusen deposits affecting the macula and peridiscal areas are seen. Histologically these deposits are external to the basement membrane of the retinal pigment epithelium and occupy the entire thickness of the Bruch membrane. Radial drusen extending into the periphery have not been found in DHRD. Zech et al. (1999) provided a 25-year follow-up of a woman diagnosed with malattia leventinese at the age of 30 years. At that time, her vision was 20/20. Eight years later, subfoveal neovascularization led to an irreversible decrease in visual acuity in her right eye, down to 20/1,000. Twenty-three years later, a dense right vitreous hemorrhage led to a further decrease in visual acuity. At that time, the left eye had a visual acuity of 20/30, and fundus examination revealed a macula identical to that of the right eye, without complication. Fu et al. (2007) studied a consanguineous Indian family in which a mother and father and their 2 sons had macular degeneration. The 2 sons exhibited significantly more severe phenotypes than either parent, particularly the older son whose retina demonstrated drusen extending beyond the posterior pole, with associated retinal degeneration.
In 5 families with Doyne honeycomb retinal dystrophy, Stone et al. (1999) found an arg345-to-trp (R345W; 601548.0001) mutation in the EFEMP1 gene. Matsumoto and Traboulsi (2001) reported a North American family with dominant radial drusen due to the ... In 5 families with Doyne honeycomb retinal dystrophy, Stone et al. (1999) found an arg345-to-trp (R345W; 601548.0001) mutation in the EFEMP1 gene. Matsumoto and Traboulsi (2001) reported a North American family with dominant radial drusen due to the R345W mutation in the EFEMP1 gene. Tarttelin et al. (2001) identified the R345W mutation in the EFEMP1 gene (601548.0001) in 7 of 10 families with Doyne honeycomb retinal dystrophy and 1 of 17 sporadic patients. No other mutations were identified. Of the 3 families without an EFEMP1 mutation, 2 were linked to 2p16. Haplotype data in the family not linked to 2p16 suggested possible linkage to a locus at 6q14. In a Swiss-Italian family in which 5 members in 3 generations had malattia leventinese, Toto et al. (2002) identified the R345W mutation in the EFEMP1 gene in 2. No mutation was identified in the EFEMP1 or the EFEMP2 gene in the other 3. Fu et al. (2007) analyzed the EFEMP1 gene in a branch of 1 of the DHRD families originally described by Stone et al. (1999) and in a consanguineous Indian family with early-onset macular degeneration, and identified the R345W mutation in affected members of both families. The sons of the Indian family, who were more severely affected than their parents, were found to be homozygous for the mutation. The haplotype of the first family was identical to all previously reported haplotypes associated with the R345W mutation, whereas the disease haplotype in the Indian family was distinctly different, suggesting that the mutation arose independently.