PATERNAL AGE AND SPORADIC NEUROFIBROMATOSIS .1. A CASE-CONTROL STUDY AND CONSIDERATION OF THE METHODOLOGIC ISSUES

Sporadic neurofibromatosis 1 (NF1) occurs in the absence of a family h istory of the disease and usually results from a new mutation in the g erm cell of one of the parents, most commonly the father. Older patern al age may increase the risk for a new germinal NF1 mutation, but the results of studies to address this question conflict. We investigated paternal age in sporadic NF1 by using a case-control study design. Pat ients who were seen at two specialty NF clinics in Houston, Texas, bor n between 1970 and 1992 and living in the Houston area and surrounding counties, were studied. Birth certificates with information on the fa ther were found for 89 cases. For each case, two birth certificates we re chosen at random from the same year and county of birth. In this wa y, the control group of 178 individuals was formed. Fathers of patient s with NF1 were 1.5 years older than fathers of control subjects at th e birth of the child, but the difference was only of borderline statis tical significance (P = 0.07). This paternal age difference was not ch anged by adjustment for socioeconomic status or maternal age. These an d previous data are consistent with either a small paternal age effect in sporadic NF1 or a bias such as that resulting from the selection o f cases and/or controls. (C) 1997 Wiley-Liss, Inc.