Aims

To report the clinical phenotype in a series of four children from three families with the rare association of high myopia, central macular atrophy, and normal full-field electroretinography (ERG).

Methods

Four male patients were ascertained with reduced vision, nystagmus, and atrophy of the macula from early childhood. Patients underwent full ophthalmic examination, electrophysiological testing, and retinal imaging.

Results

Minimum duration of follow-up was 8 years. At last review, visual acuity ranged from 0.22 to 1.20 logMAR (6/9.5-6/95 Snellen) at a mean age of 10.5 years (median 9.5 years, range 9-14 years). Refractive error ranged from a spherical equivalent of -7.40 D to -24.00 D. Three had convergent squint. Fundus examination and imaging demonstrated bilateral macular atrophy in all patients that varied from mild atrophy of the retinal pigment epithelium (RPE) to well-demarcated, punched-out atrophic lesions of retina, RPE, and choroid. Flash ERG was normal under photopic and scotopic conditions in all patients. Pattern ERG, performed in three patients, was consistent with mild to severe macular dysfunction. Progression of the area of atrophy was evident in one patient and of the myopia in two patients but all patients had stable visual acuity.

Conclusions

Patients with congenital high myopia and macular atrophy present in infancy with reduced visual acuity and nystagmus. The macular atrophic lesions vary in size and severity but electrophysiological testing is consistent with dysfunction confined to the macula. There was no deterioration in visual acuity over 8-10 years of monitoring.

Purpose

The purpose of this study is to describe the phenotype of a family with de novo mutation in the GUCY2D.

Materials and methods

Five subjects, including two monozygotic twins, underwent ophthalmic clinical examination while some had autofluorescence imaging (AF) and optical coherence tomography (OCT). Symptomatic individuals underwent electrophysiological testing. The youngest subject (21 years) was also evaluated psychophysically. DNA obtained from the individuals was screened for mutations in GUCY2D. Microsatellite markers were used to determine the haplotype of 17p surrounding the GUCY2D gene.

Results

The youngest subject had 6/18 visual acuity, an annulus of hyper-autofluorescence in the perifoveal region, and a subfoveal absence of outer segments on OCT. In the older individuals, severe thinning of inner retina and a patchy loss of photoreceptors and retinal pigment epithelium were observed in the perifoveal region. All three showed generalised cone system dysfunction with preserved rod function on electrophysiology. Psychophysical evaluation was consistent with poor cone function. Screening of the GUCY2D gene revealed the mutation p.R838H in all the affected individuals and was absent in the asymptomatic patients. Haplotyping showed that the mutation originated from the unaffected mother.

Conclusions

Autosomal dominant cone dystrophy due to GUCY2D can occur without a history in the antecedents due to a de novo mutation. This is important to consider in any simplex case with a similar phenotype. The phenotype description of this disorder is expanded with detailed description of the OCT findings. This paper describes the concordance of the phenotypic findings in the monozygotic twins.

Leber inherited optic neuropathy (LHON) is characterized by subacute bilateral loss of central vision due to dysfunction and loss of retinal ganglion cells (RGCs). Comprehensive visual electrophysiological investigations (including pattern reversal visual evoked potentials, pattern electroretinography and the photopic negative response) performed on 13 patients with acute and chronic LHON indicate early impairment of RGC cell body function and severe axonal dysfunction. Temporal, spatial and chromatic psychophysical tests performed on 7 patients with acute LHON and 4 patients with chronic LHON suggest severe involvement or loss of the midget, parasol and bistratified RGCs associated with all three principal visual pathways.

To describe the clinical and molecular characteristics of patients with childhood-onset Stargardt disease (STGD).Retrospective case series.Forty-two patients who were diagnosed with STGD in childhood at a single institution between January 2001 and January