Establishing the genetic heterogeneity of familial hemiplegic migraine

In this issue of Brain Thomsen and colleagues present data representing several important developments in the field of familial hemiplegic migraine (FHM) with their investigation of the genetic spectrum and prevalence of this disorder (Thomsen et al ., 2006). The authors have performed the first population-based sampling strategy to obtain complete case ascertainment of this rare disease (Lykke Thomsen et al ., 2002) and followed this initial effort with a complete molecular genetic analysis of the collected samples, both by searching for mutation at the three identified FHM loci (Ophoff et al ., 1996; De Fusco et al ., 2003; Dichgans et al ., 2005) and also by performing a genome wide linkage scan. These data allow expansion and refinement of the genetic etiology of FHM within the relatively homogenous Danish population. Specifically, they clarify the penetrance of each mutation, population prevalence of mutations in genes known to cause this disorder, identify novel mutations and also show data that suggest additional as yet unidentified genetic lesions underlying this disorder. From a clinical perspective the study provides valuable data on the potential contribution of these mutations in defining the phenotypic (clinical) spectrum of this disorder. The hope is that these innovations will someday be extended to FHM's highly prevalent cousin, the common migraine.The extent of sampling in this study distinguishes it from others since the aim was to capture every FHM family in Denmark by systematic selection through the national patient registry, headache clinics, and advertising in national journals to physicians and headache patients. Sampling for families …