title: Clinical and molecular characterization of enhanced S-cone syndrome in children.
abstract: OBJECTIVE
  Enhanced S-cone syndrome (ESCS) forms part of the differential diagnosis of night blindness in childhood.
  
  
  OBJECTIVE
  To report in detail the clinical phenotype and molecular genetic findings in a series of children with ESCS.
  
  
  METHODS
  Nine children with ESCS from 5 families underwent full ophthalmic examination, electrophysiological testing, and retinal imaging at a genetic eye disease clinic of a tertiary referral eye hospital. Bidirectional Sanger sequencing of all exons and intron-exon boundaries of NR2E3 was performed.
  
  
  METHODS
  Results of ophthalmic examination and sequence analysis of NR2E3.
  
  
  RESULTS
  In total, 5 girls and 4 boys with a diagnosis of ESCS were included in the study. All patients had developed nyctalopia from early childhood. Visual acuity ranged from 0.00 to 1.20 logMAR (20/20 to 20/320 Snellen). All patients had hyperopia. Three patients had nummular pigmentary lesions along the arcades as typically seen in adults, 4 patients had mild pigmentary disturbance or white dots along the arcades, and 2 patients had a normal retinal appearance, although their fundus autofluorescence imaging demonstrated foci of increased autofluorescence along the arcades. Three patients had macular schisis-like changes on optical coherence tomography. Eight patients had electrophysiological testing at a mean age of 8.6 years (age range, 3-14 years), and in each patient the findings were consistent with the diagnosis of ESCS. Direct sequencing of NR2E3 identified 3 previously described mutations and 4 novel mutations. Seven patients were compound heterozygous for mutations in NR2E3, and 2 additional sibling patients were presumed to be homozygous for a missense change based on parental sequencing.
  
  
  CONCLUSIONS
  In this sample, children with ESCS had an early onset of night blindness and hyperopia but no nystagmus. Based on this study, children with ESCS may initially manifest a normal fundus appearance but later develop mottled retinal pigment epithelium change along the arcades, followed by the appearance of white dots in the same distribution. Fundus autofluorescence imaging is abnormal in children with a normal fundus appearance. The electrophysiological findings are pathognomonic and allow targeted molecular screening and a specific diagnosis.
authors: Inherited Eye Diseases, University College London Institute of Ophthalmology, London, England2Moorfields Eye Hospital, London, England.
authors: Sarah
authors: S
authors: Hull
authors: Inherited Eye Diseases, University College London Institute of Ophthalmology, London, England.
authors: Gavin
authors: G
authors: Arno
authors: Inherited Eye Diseases, University College London Institute of Ophthalmology, London, England2Moorfields Eye Hospital, London, England.
authors: Panagiotis I
authors: PI
authors: Sergouniotis
authors: Sunderland Eye Infirmary, Sunderland, England.
authors: Peter
authors: P
authors: Tiffin
authors: Inherited Eye Diseases, University College London Institute of Ophthalmology, London, England2Moorfields Eye Hospital, London, England.
authors: Arundhati Dev
authors: AD
authors: Borman
authors: Inherited Eye Diseases, University College London Institute of Ophthalmology, London, England2Moorfields Eye Hospital, London, England.
authors: Aman
authors: A
authors: Chandra
authors: Inherited Eye Diseases, University College London Institute of Ophthalmology, London, England2Moorfields Eye Hospital, London, England.
authors: Anthony G
authors: AG
authors: Robson
authors: Inherited Eye Diseases, University College London Institute of Ophthalmology, London, England2Moorfields Eye Hospital, London, England.
authors: Graham E
authors: GE
authors: Holder
authors: Inherited Eye Diseases, University College London Institute of Ophthalmology, London, England2Moorfields Eye Hospital, London, England.
authors: Andrew R
authors: AR
authors: Webster
authors: Inherited Eye Diseases, University College London Institute of Ophthalmology, London, England2Moorfields Eye Hospital, London, England.
authors: Anthony T
authors: AT
authors: Moore
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004596:Electroretinography; D015785:Eye Diseases, Hereditary / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D008297:Male; D008967:Molecular Biology; D009154:Mutation; D009755:Night Blindness / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D057093:Orphan Nuclear Receptors / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012162:Retinal Degeneration / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D041623:Tomography, Optical Coherence; D014786:Vision Disorders / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D014792:Visual Acuity / Q000502:physiology
chemical_list: D005136:Eye Proteins; C403073:NR2E3 protein, human; D057093:Orphan Nuclear Receptors