The clinical, electrophysiological and genetic features of 93 patients (41 males, 52 females) from 37 unrelated families with X-linked dominant Charcot-Marie-Tooth (CMTX) disease are reported from the Hopital de la Salpetriere, Paris, France. Age at onset was younger in males than females: 15.4 +/-9.6 yrs vs 18.7 +/-13.1 yrs. The respective age ranges of onset were 1-40 yrs in males and 1-56 yrs in females (P=0.22). Onset before age 10 years occurred in 27% of males and 15% of females. Disease duration at time of examination was shorter in males than females: 18.3 +/- 14.6 yrs in males and 23.9 +/- 13.7 yrs in females (P=0.11). Males were more severely affected than females and had higher functional disability scores; they had more frequent muscle weakness, amyotrophy, proprioception loss, upper limb areflexia, and pes cavus. Females were more frequently asymptomatic than males (29% vs 11%). Motor nerve conduction velocities, distal motor latencies, and compound muscle action potentials were slower, longer and lower, respectively, in males compared to females. In molecular genetic testing, 27 different CX32 mutations and one entire deletion of the CX32 coding sequence were present in the 37 families. Patients with age at onset before 10 years presented nonfunctional mutations, and the type of mutation influences the phenotype. [1]

COMMENT. In this large series of patients with CMTX, differences between male and female patients are more apparent than in previous studies. Males are more severely affected than females, and onset before 10 years is also more frequent in males than females, occurring in 27% and 15% of patients, respectively. Patients with early onset present nonfunctional genetic mutations. These gender differences are also reflected in electrophysiological findings.