Assessment of the phenotypic range seen in Doyne honeycomb retinal dystrophy
K. Evans, C. Y. Gregory, S. D. Wijesuriya, S. Kermani, M. R. Jay, C. Plant and A. C. Bird
Department of Clinical Ophthalmology, Moorfields Eye Hospital, London, England. kevans@hgmp.mrc.ac.uk
OBJECTIVE: Using molecular genetics as the basis for diagnosis, to assess
the phenotype in the family originally described as having dominantly
inherited Doyne honeycomb retinal dystrophy (DHRD) linked to chromosome
2p16. DESIGN: Clinical examination including fluorescein angiography was
undertaken in 107 family members. Nine affected patients underwent
electroretinography, perimetry, dark adaptometry, color-contrast
sensitivity measurement, and autofluorescent fundus imaging. PATIENTS: The
disease-associated haplotype used to allocate disease status was based on
our further refinement of the DHRD locus to between loci D2S2739 and
D2S378. The study identified 50 affected patients. In addition, 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
radiated 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 drusen.
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 severity 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.
