The clinical spectrum of neurofibromatosis 2 (NF2) at the time of presymptomatic DNA diagnosis in at-risk first-degree relatives in five families were studied at the Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, and the Neurofibromatosis Institute, La Crescenta, CA. With molecular genetic analysis, 11 first-degree relatives were predicted to be at high risk, and 20 at low risk of carrying an NF2 mutation. Five mutation carriers, including a 31-year-old, had no clinical manifestations, while 4, including a 7-year-old, had vestibular schwannomas (VS), early-onset cataracts, or both. The identification of presymptomatic NF2 mutation carriers by DNA diagnosis permits improved genetic counselling and clinical management in at-risk subjects. The early detection of VS by gadolinium-enhanced MRI can improve surgical outcome. [1]
COMMENT. In NF2 mutation carriers, DNA testing may lead to early diagnosis, and optimal treatment and counselling. However, ethical factors must be considered in testing children because of health insurance and other discriminating issues.