title: Clinical course, genetic etiology, and visual outcome in cone and cone-rod dystrophy.
abstract: OBJECTIVE
  To evaluate the clinical course, genetic etiology, and visual prognosis in patients with cone dystrophy (CD) and cone-rod dystrophy (CRD).
  
  
  METHODS
  Clinic-based, longitudinal, multicenter study.
  
  
  METHODS
  Consecutive probands with CD (N = 98), CRD (N = 83), and affected relatives (N = 41 and N = 17, respectively) from various ophthalmogenetic clinics in The Netherlands, Belgium, and the United Kingdom.
  
  
  METHODS
  Data on best-corrected Snellen visual acuity, color vision, ophthalmoscopy, fundus photography, Goldmann perimetry, and full-field standard electroretinogram (ERG) from all patients were registered from medical charts over a mean follow-up of 19 years. The ABCA4, CNGB3, KCNV2, PDE6C, and RPGR genes were analyzed by direct sequencing in autosomal recessive (AR) and X-linked (XL), respectively. Genotyping was not undertaken for autosomal-dominant cases.
  
  
  METHODS
  The 10-year progression of all clinical parameters and cumulative lifetime risk of low vision and legal blindness were assessed.
  
  
  RESULTS
  The mean age onset for CD was 16 years (standard deviation, 11), and of CRD 12 years (standard deviation, 11; P = 0.02). The pattern of inheritance was AR in 92% of CD and 90% of CRD. Ten years after diagnosis, 35% of CD and 51% of CRD had a bull's eye maculopathy; 70% of CRD showed absolute peripheral visual field defects and 37% of CD developed rod involvement on ERG. The mean age of legal blindness was 48 (standard error [SE], 3.1) years in CD, and 35 (SE, 1.1; P<0.001) years in CRD. ABCA4 mutations were found in 8 of 90 (9%) of AR-CD, and in 17 of 65 (26%) of AR-CRD. Other mutations were detected in CNGB3 (3/90; 3%), KCNV2 (4/90; 4%), and in PDE6C (1/90; 1%). The RPGR gene was mutated in the 2 XL-CD and in 4 of 5 (80%) of XL-CRD. ABCA4 mutations as well as age of onset <20 years were significantly associated with a faster progression to legal blindness (P<0.001).
  
  
  CONCLUSIONS
  Although CD had a slightly more favorable clinical course than CRD, both disorders progressed to legal blindness in the majority of patients. Mutations in the ABCA4 gene and early onset of disease were independent prognostic parameters for visual loss. Our data may serve as an aid in counseling patients with progressive cone disorders.
authors.affiliation: Department of Ophthalmology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Alberta A H J
authors.initials: AA
authors.lastname: Thiadens
authors.forename: T My Lan
authors.initials: TM
authors.lastname: Phan
authors.forename: Renate C
authors.initials: RC
authors.lastname: Zekveld-Vroon
authors.forename: Bart P
authors.initials: BP
authors.lastname: Leroy
authors.forename: L Ingeborgh
authors.initials: LI
authors.lastname: van den Born
authors.forename: Carel B
authors.initials: CB
authors.lastname: Hoyng
authors.forename: Caroline C W
authors.initials: CC
authors.lastname: Klaver
authors.forename: Susanne
authors.initials: S
authors.lastname: Roosing
authors.forename: Jan-Willem R
authors.initials: JW
authors.lastname: Pott
authors.forename: Mary J
authors.initials: MJ
authors.lastname: van Schooneveld
authors.forename: Norka
authors.initials: N
authors.lastname: van Moll-Ramirez
authors.forename: Maria M
authors.initials: MM
authors.lastname: van Genderen
authors.forename: Camiel J F
authors.initials: CJ
authors.lastname: Boon
authors.forename: Anneke I
authors.initials: AI
authors.lastname: den Hollander
authors.forename: Arthur A B
authors.initials: AA
authors.lastname: Bergen
authors.forename: Elfride
authors.initials: E
authors.lastname: De Baere
authors.forename: Frans P M
authors.initials: FP
authors.lastname: Cremers
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lotery
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000293:Adolescent; D017668:Age of Onset; D001766:Blindness / Q000503:physiopathology; D002648:Child; D003117:Color Vision Defects / Q000503:physiopathology; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6 / Q000235:genetics; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000235:genetics; D004252:DNA Mutational Analysis; D004596:Electroretinography; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009154:Mutation; D009887:Ophthalmoscopy; D016133:Polymerase Chain Reaction; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000503:physiopathology; D015354:Vision, Low / Q000503:physiopathology; D014792:Visual Acuity / Q000502:physiology*; D058609:Visual Field Tests
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters; C415904:CNGB3 protein, human; D054815:Cyclic Nucleotide-Gated Cation Channels; D005136:Eye Proteins; C489610:KCNV2 protein, human; D024642:Potassium Channels, Voltage-Gated; C099929:RPGR protein, human; D054707:Cyclic Nucleotide Phosphodiesterases, Type 6; C096885:PDE6C protein, human