EPILEPSY AND MENTAL-RETARDATION IN A SUBSET OF EARLY-ONSET 4Q35-FACIOSCAPULOHUMERAL MUSCULAR-DYSTROPHY

The gene for facioscapulohumeral muscular dystrophy (FSHD) has been ma pped to chromosome 4q35. In most patients with FSHD, a deletion of 3.3 kb tandemly repeated units within the EcoRI fragment that can be dete cted by probe p13E-11 is associated with the disease. To elucidate the relation between the phenotype and the genotype in FSHD, we examined 91 Japanese unrelated families with a clinical diagnosis of FSHD (140 patients, 205 healthy individuals). Of these, 78 families (86%) had 4q 35-FSHD (127 patients), in which 20 patients (20/127, 16%) were classi fied as early onset FSHD. We found that all nine patients with the sma llest EcoRI fragments (10 to 11 kb) were classified among the early on set group (9/20, 45%), and these patients showed a high frequency of b oth epilepsy (4/9, 44%) and mental retardation (8/9, 89%). In contrast , none of the remaining patients with 4q35-FSHD had epilepsy or mental retardation. We conclude that FSHD patients with a large gene deletio n in the FSHD gene region tend to have a higher chance of showing seve re clinical phenotypes with CNS abnormalities. This finding may have p ractical implications for genetic counseling, although the molecular g enetic background remains unclear.