A pedigree of Leber's hereditary optic neuropathy with visual loss in childhood, primarily in girls

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 a trophy 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. Conclusion: 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.