title: Autosomal recessive bestrophinopathy: differential diagnosis and treatment options.
abstract: OBJECTIVE
  To describe the clinical and genetic characteristics of patients with autosomal recessive bestrophinopathy (ARB).
  
  
  METHODS
  Retrospective case series.
  
  
  METHODS
  Ten patients with ARB from 7 different families.
  
  
  METHODS
  All patients underwent a complete ophthalmic examination, including dilated fundus examination, fundus photography, and fluorescein angiography (FA). In all probands, fundus autofluorescence (FAF) imaging, spectral-domain optical coherence tomography (OCT), full-field electroretinography (ERG), electro-oculography (EOG), and Goldmann perimetry were performed. In selected patients, multifocal ERG was performed. Blood samples were obtained to analyze the BEST1 gene for biallelic mutations that confirmed the diagnosis of ARB.
  
  
  METHODS
  Age at onset; visual acuity; fundus appearance; characteristics on FA, FAF, OCT, full-field ERG, and EOG; BEST1 gene mutations; and genotype-phenotype correlation.
  
  
  RESULTS
  The age at onset varied widely, from 2 to 54 years. A spectrum of fundus abnormalities was observed, such as multifocal yellowish subretinal deposits, subretinal fibrous scars, and cystoid intraretinal fluid collections in the macula. All ARB patients were hyperopic, and some had shallow anterior chamber angles that predisposed them to angle-closure glaucoma. The EOG results were abnormal in all patients. The full-field ERG results were abnormal in 8 ARB patients, whereas 2 patients demonstrated normal cone and rod responses on full-field ERG. Nine ARB patients carried biallelic mutations in the BEST1 gene, and in 1 patient with a characteristic ARB phenotype, only 1 mutation could be identified. Seven different mutations were detected, including 4 novel mutations.
  
  
  CONCLUSIONS
  Autosomal recessive bestrophinopathy is a recognizable phenotype caused by autosomal recessively inherited mutations in the BEST1 gene. A differential diagnosis with other conditions can be made on the basis of marked autofluorescence changes in combination with an absent light rise on the EOG that outweighs the full-field ERG abnormalities, which point to the BEST1-related hereditary nature of the disease. A number of currently available therapeutic options should be considered in ARB, a disease that seems to be a suitable candidate for future gene therapy.
authors.affiliation: Department of Ophthalmology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. c.boon@ohk.umcn.nl
authors.forename: Camiel J F
authors.initials: CJ
authors.lastname: Boon
authors.forename: L Ingeborgh
authors.initials: LI
authors.lastname: van den Born
authors.forename: Linda
authors.initials: L
authors.lastname: Visser
authors.forename: Jan E E
authors.initials: JE
authors.lastname: Keunen
authors.forename: Arthur A B
authors.initials: AA
authors.lastname: Bergen
authors.forename: Judith C
authors.initials: JC
authors.lastname: Booij
authors.forename: Frans C
authors.initials: FC
authors.lastname: Riemslag
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Florijn
authors.forename: Mary J
authors.initials: MJ
authors.lastname: van Schooneveld
mesh_terms: D000293:Adolescent; D000328:Adult; D000075002:Bestrophins; D002648:Child; D002675:Child, Preschool; D018118:Chloride Channels / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D004585:Electrooculography; D004596:Electroretinography; D015785:Eye Diseases, Hereditary / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D056726:Genetic Association Studies; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D012160:Retina / Q000473:pathology* / Q000503:physiopathology; D012164:Retinal Diseases / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy*; D012189:Retrospective Studies; D041623:Tomography, Optical Coherence; D014792:Visual Acuity; D055815:Young Adult
chemical_list: C113133:BEST1 protein, human; D000075002:Bestrophins; D018118:Chloride Channels; D005136:Eye Proteins; D004247:DNA