title: A pedigree of Leber's hereditary optic neuropathy with visual loss in childhood, primarily in girls.
abstract: BACKGROUND
  Leber's hereditary optic neuropathy (LHON) mostly affects young males. In patients carrying one of the primary mutations the risk to develop LHON is 50% for males and 10% for females. We report a family with predominantly young girls affected.
  
  
  METHODS
  In a family with 14 known maternal relatives (11 females, 3 males) 9 patients in 4 generations developed LHON. Eight of the 9 patients were females. Three affected females could be examined and followed.
  
  
  RESULTS
  The only affected male showed the typical course of LHON with acute visual loss in both eyes (20/400-20/800) within 6 weeks at 20 years of age. Eight of 9 females developed signs of LHON. In these females acute visual loss occurred at about 10 years of age. Final visual acuity was about 20/200. Central or paracentral scotomata, color vision defects and delayed P100 latencies in the VEP were seen. Ophthalmoscopy showed hyperemic discs in the acute stage and optic atrophy in later stages. Molecular genetic analysis revealed the presence of the mtDNA ND4/np11778 mutation in this family. Specific clinical or additional molecular genetic risk factors could not be detected.
  
  
  CONCLUSIONS
  Families with LHON may show considerable variations of the clinical course and the gender- or age-specific risk. We present a family with a high disease penetrance of 64% and a 2 times higher risk for young females than for males. Furthermore, early visual loss in this family is permanent.
authors.affiliation: Eye Department, Universitäts-Klinikum Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, D-12200 Berlin, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Thieme
authors.forename: B
authors.initials: B
authors.lastname: Wissinger
authors.forename: C
authors.initials: C
authors.lastname: Jandeck
authors.forename: M
authors.initials: M
authors.lastname: Christ-Adler
authors.forename: H
authors.initials: H
authors.lastname: Kraus
authors.forename: U
authors.initials: U
authors.lastname: Kellner
authors.forename: M H
authors.initials: MH
authors.lastname: Foerster
mesh_terms: D000328:Adult; D002648:Child; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D006801:Humans; D008297:Male; D015418:Optic Atrophies, Hereditary / Q000150:complications* / Q000235:genetics; D010375:Pedigree; D014786:Vision Disorders / Q000209:etiology* / Q000503:physiopathology; D014792:Visual Acuity; D014794:Visual Fields
chemical_list: D004272:DNA, Mitochondrial