title: Early-onset stargardt disease: phenotypic and genotypic characteristics.
abstract: OBJECTIVE
  To describe the phenotype and genotype of patients with early-onset Stargardt disease.
  
  
  METHODS
  Retrospective cohort study.
  
  
  METHODS
  Fifty-one Stargardt patients with age at onset ≤10 years.
  
  
  METHODS
  We reviewed patient medical records for age at onset, medical history, initial symptoms, best-corrected visual acuity (BCVA), ophthalmoscopy, fundus photography, fundus autofluorescence (FAF), fluorescein angiography (FA), spectral-domain optical coherence tomography (SD-OCT), and full-field electroretinography (ffERG). The ABCA4 gene was screened for mutations.
  
  
  METHODS
  Age at onset, BCVA, fundus appearance, FAF, FA, SD-OCT, ffERG, and presence of ABCA4 mutations.
  
  
  RESULTS
  The mean age at onset was 7.2 years (range, 1-10). The median times to develop BCVA of 20/32, 20/80, 20/200, and 20/500 were 3, 5, 12, and 23 years, respectively. Initial ophthalmoscopy in 41 patients revealed either no abnormalities or foveal retinal pigment epithelium (RPE) changes in 10 and 9 patients, respectively; the other 22 patients had foveal atrophy, atrophic RPE lesions, and/or irregular yellow-white fundus flecks. On FA, there was a "dark choroid" in 21 out of 29 patients. In 14 out of 50 patients, foveal atrophy occurred before flecks developed. On FAF, there was centrifugal expansion of disseminated atrophic spots, which progressed to the eventual profound chorioretinal atrophy. Spectral-domain OCT revealed early photoreceptor damage followed by atrophy of the outer retina, RPE, and choroid. On ffERG in 26 patients, 15 had normal amplitudes, and 11 had reduced photopic and/or scotopic amplitudes at their first visit. We found no correlation between ffERG abnormalities and the rate of vision loss. Thirteen out of 25 patients had progressive ffERG abnormalities. Finally, genetic screening of 44 patients revealed ≥2 ABCA4 mutations in 37 patients and single heterozygous mutations in 7.
  
  
  CONCLUSIONS
  In early-onset Stargardt, initial ophthalmoscopy can reveal no abnormalities or minor retinal abnormalities. Yellow-white flecks can be preceded by foveal atrophy and may be visible only on FAF. Although ffERG is insufficient for predicting the rate of vision loss, abnormalities can develop. Over time, visual acuity declines rapidly in parallel with progressive retinal degeneration, resulting in profound chorioretinal atrophy. Thus, early-onset Stargardt lies at the severe end of the spectrum of ABCA4-associated retinal phenotypes.
authors.affiliation: Department of Ophthalmology, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Stanley
authors.initials: S
authors.lastname: Lambertus
authors.affiliation: Department of Ophthalmology, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Ramon A C
authors.initials: RA
authors.lastname: van Huet
authors.affiliation: Department of Ophthalmology, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Nathalie M
authors.initials: NM
authors.lastname: Bax
authors.affiliation: Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Lies H
authors.initials: LH
authors.lastname: Hoefsloot
authors.affiliation: Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands; Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: Frans P M
authors.initials: FP
authors.lastname: Cremers
authors.affiliation: Department of Ophthalmology, Radboud university medical center, Nijmegen, The Netherlands; Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Camiel J F
authors.initials: CJ
authors.lastname: Boon
authors.affiliation: Department of Ophthalmology, Radboud university medical center, Nijmegen, The Netherlands.
authors.forename: B Jeroen
authors.initials: BJ
authors.lastname: Klevering
authors.affiliation: Department of Ophthalmology, Radboud university medical center, Nijmegen, The Netherlands. Electronic address: Carel.Hoyng@radboudumc.nl.
authors.forename: Carel B
authors.initials: CB
authors.lastname: Hoyng
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005260:Female; D005451:Fluorescein Angiography; D005838:Genotype; D006801:Humans; D007223:Infant; D008268:Macular Degeneration / Q000151:congenital* / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009887:Ophthalmoscopy; D010641:Phenotype; D012189:Retrospective Studies; D000080362:Stargardt Disease; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology; D055815:Young Adult
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters