Generalized Choriocapillaris Dystrophy, a Distinct Phenotype in the Spectrum of ABCA4-Associated Retinopathies

TY - JOUR

T1 - Generalized Choriocapillaris Dystrophy, a Distinct Phenotype in the Spectrum of ABCA4-Associated Retinopathies

AU - Bertelsen, Mette

AU - Zernant, Jana

AU - Larsen, Michael

AU - Duno, Morten

AU - Allikmets, Rando

AU - Rosenberg, Thomas

PY - 2014/4/8

Y1 - 2014/4/8

N2 - PURPOSE: We describe a particular form of autosomal recessive generalized choriocapillaris dystrophy phenotype associated with ABCA4 mutations.METHODS: A cohort of 30 patients with identified ABCA4 mutations and a distinct phenotype was studied. A retrospective review of history, fundus photographs, electroretinography, visual field testing, dark adaptometry, and optical coherence tomography was performed. Genetic analyses were performed by ABCA4 microarray analysis, high resolution melting, and/or next generation sequencing of all protein-coding sequences of the ABCA4 gene.RESULTS: The earliest recorded manifestation of ABCA4-associated disease was a central bull's eye type of macular dystrophy that progressed to chorioretinal atrophy of the macula with coarse rounded hyperpigmentations and expanding involvement of the periphery. The mean age at first presentation was 10.3 years, the longest follow-up was 61 years. All patients had two ABCA4 mutations identified, confirming the molecular genetic diagnosis of an ABCA4-associated disease. Most patients harbored at least one mutation classified as "severe," the most common of which was the p.N965S variant that had been found previously at a high frequency among patients with ABCA4-associated retinal dystrophies in Denmark.CONCLUSIONS: Generalized choriocapillaris dystrophy is a progressive ABCA4-associated phenotype characterized by early-onset macular dystrophy that disperses and expands to widespread end-stage chorioretinal atrophy with profound visual loss. All cases in this study were confirmed as harboring two ABCA4 mutations. Most of the ABCA4 mutations were classified as "severe" explaining the early onset, panretinal degeneration, and fast progression of the disease.

AB - PURPOSE: We describe a particular form of autosomal recessive generalized choriocapillaris dystrophy phenotype associated with ABCA4 mutations.METHODS: A cohort of 30 patients with identified ABCA4 mutations and a distinct phenotype was studied. A retrospective review of history, fundus photographs, electroretinography, visual field testing, dark adaptometry, and optical coherence tomography was performed. Genetic analyses were performed by ABCA4 microarray analysis, high resolution melting, and/or next generation sequencing of all protein-coding sequences of the ABCA4 gene.RESULTS: The earliest recorded manifestation of ABCA4-associated disease was a central bull's eye type of macular dystrophy that progressed to chorioretinal atrophy of the macula with coarse rounded hyperpigmentations and expanding involvement of the periphery. The mean age at first presentation was 10.3 years, the longest follow-up was 61 years. All patients had two ABCA4 mutations identified, confirming the molecular genetic diagnosis of an ABCA4-associated disease. Most patients harbored at least one mutation classified as "severe," the most common of which was the p.N965S variant that had been found previously at a high frequency among patients with ABCA4-associated retinal dystrophies in Denmark.CONCLUSIONS: Generalized choriocapillaris dystrophy is a progressive ABCA4-associated phenotype characterized by early-onset macular dystrophy that disperses and expands to widespread end-stage chorioretinal atrophy with profound visual loss. All cases in this study were confirmed as harboring two ABCA4 mutations. Most of the ABCA4 mutations were classified as "severe" explaining the early onset, panretinal degeneration, and fast progression of the disease.

KW - ATP-Binding Cassette Transporters

KW - Adolescent

KW - Adult

KW - Alleles

KW - Child

KW - Choroid

KW - DNA

KW - DNA Mutational Analysis

KW - Female

KW - Fluorescein Angiography

KW - Follow-Up Studies

KW - Fundus Oculi

KW - Genotype

KW - Humans

KW - Macular Degeneration

KW - Male

KW - Middle Aged

KW - Mutation

KW - Pedigree

KW - Time Factors

KW - Tomography, Optical Coherence

KW - Young Adult

U2 - 10.1167/iovs.13-13391

DO - 10.1167/iovs.13-13391

M3 - Journal article

C2 - 24713488

SN - 0146-0404

VL - 55

SP - 2766

EP - 2776

JO - Investigative Ophthalmology & Visual Science

JF - Investigative Ophthalmology & Visual Science

IS - 4

ER -