Assessment of the Phenotypic Range Seen in Doyne Honeycomb Retinal Dystrophy Kevin Evans, MD; Cheryl Y. Gregory, PhD; Sujeewa D. Wijesuriya, PhD; Sana Kermani; Marcelle R. Jay, PhD; Catherine Plant; Alan C. Bird, MD Objective: Using molecular genetics as the basis for di- agnosis, to assess the phenotype in the family originally described as having dominantly inherited Doyne hon- eycomb retinal dystrophy (DHRD) linked to chromo- some 2p16. Design: Clinical examination including fluorescein an- giography was undertaken in 107 family members. Nine affected patients underwent electroretinography, perim- etry, dark adaptometry, color-contrast sensitivity mea- surement, and autofluorescent fundus imaging. Patients: The disease-associated haplotype used to al- locate disease status was based on our further refine- ment of the DHRD locus to between loci D2S2739 and D2S378. The study identified 50 affected patients. In ad- dition, previously published information on a further 8 individuals was used. The study population represented 6 generations of a 9-generation pedigree. Results: Three types of deposits were seen: large, soft drusen at the macula and abutting the optic nerve head; small, hard deposits that in some patients radi- ated from the macula; and autofluorescent deposits. Most younger affected individuals exhibited small hard drusen only at the macula and had normal visual function. Information on 2 patients suggested that DHRD can be a cause of childhood-onset blindness. Advanced disease was associated with severe visual loss and posterior pole atrophy without signs of dru- sen. Advanced age was not invariably associated with severe visual loss. Conclusions: Previously identified characteristics of DHRD were confirmed and new features identified. Contrary to previous reports, the constancy and sever- ity of radial (basal laminar) drusen seen clinically are the only features that can be used to differentiate between DHRD and malattia leventinese. The highly variable phenotype suggests that the influence of the DHRD-mutant gene may be modulated by other genetic and/or environmental factors. Arch Ophthalmol. 1997;115:904-910 THE DOMINANT drusen pheno¬ type represents an unknown number of genetically dis¬ tinct entities, some of which have been labeled as epony¬ mous diseases. ' The first of these to convinc¬ ingly demonstrate autosomal dominant in¬ heritance was Doyne honeycomb retinal dys¬ trophy (DHRD), described by Robert W. Doyne in 1899.2 Further studies have con¬ firmed and extended this initial work.3"9 Recently, DHRD has been mapped to chromosome 2pl6,10 overlapping the re¬ gion previously ascribed to contain the ge¬ netic mutation causing malattia leventi¬ nese,11 another autosomal dominant drusen phenotype. This has raised the pos¬ sibility that these 2 conditions may de¬ rive from allelic mutations of the same gene. It has also been suggested that the 2 conditions may in fact be clinically in¬ distinguishable.11 Genealogy has established that 4 of the originally described DHRD families9 are in fact branches of 1 large pedigree.12 Working with this extended pedigree, a 2-part study was undertaken. First, using molecular genetic haplotype data as the ba¬ sis for disease-status allocation, the range of phenotypic expression was assessed. Second, detailed clinical information was compared with published data on the clini¬ cal characteristics of malattia leventinese to determine whether these 2 epony¬ mous phenotypes are actually clinically distinct. The importance of these disor¬ ders lies in their potential homology with age-related macular degeneration. RESULTS Fifty individuals who carried the disease- associated haplotype between marker loci D2S2739 and D2S378 were allocated as From the Departments of Clinical Ophthalmology (Drs Evans, Jay, and Bird and Ms Plant) and Molecular Genetics (Drs Gregory and Wijesuriya and Ms Kermani), Institute of Ophthalmology and Moorfields Eye Hospital, London, England. Downloaded From: http://archopht.jamanetwork.com/ by a University of British Columbia Library User on 02/18/2014