Familial neurofibromatosis type 1: clinical experience with DNA testing

To determine how DNA testing for familial neurofibromatosis type 1 (NF-1) would be used in a clinical setting by patients and physicians, we performed confirmatory DNA testing on 24 individuals with a family history of NF-1 and on nine couples who requested DNA testing for current or future prenatal diagnosis. A further eight families were unsuitable for DNA linkage testing because of their pedigree structure. For the majority of persons the certainty of the test result was 95% to 99%. In five individuals, only one of whom was less than 6 years of age, the DNA-based diagnosis was discrepant with the clinical diagnosis at the time of referral. In all five cases, results of subsequent clinical re-examinations were consistent with the DNA diagnosis. We conclude that DNA testing by linkage analysis may be most useful as an adjunct to the clinical diagnosis of familial NF-1 (1) in children less than 6 years of age in whom the full manifestations may not yet be apparent, (2) in NF-1 families interested in prenatal testing, and (3) when the resources available for a complete clinical examination are limited.