Researchers at Wayne State University School of Medicine, Detroit, MI, identified distinguishing clinical and physiological features of subtypes of Charcot-Marie-Tooth (CMT) disease among 787 patients that could be used to direct genetic testing. A total of 527 patients with CMT (67%) received a genetic subtype, while 260 had no identifiable mutation. The most common CMT subtypes were CMT1A, CMT1X, hereditary neuropathy with pressure palsies (HNPP), CMT1B, and CMT2A. Other subtypes accounted for <1% each. Eleven patients had >1 genetically identified subtype of CMT. Genetically identified CMT patients were separable into specific groups based on age of onset and degree of slowing of motor nerve conduction velocities. A focused approach based on phenotype, physiology and prevalence is proposed for genotyping. With a genetic diagnosis made in a patient, other family members can be identified by clinical and neurophysiology evaluation, and costly genetic tests may be unnecessary. [1]

COMMENT. CMT affecting 1 in 2500 population is the most common inherited neurological disorder. Generally autosomal dominant in inheritance, some cases are X-linked or autosomal recessive inheritance. Demyelinating neuropathy is most common, but one-third are primary axonal disorders [2, 3]. CMT is a heterogeneous disorder, and more than 30 genes have been identified that cause various clinical and physiological subtypes. The focused approach to diagnosis outlined by the above authors should facilitate family planning, prognosis, and treatment.

X-linked CMT disease in childhood. A retrospective review of 17 children with CMTX at children’s hospitals in Melbourne and Sydney, Australia, showed that 15 were symptomatic before 5 years of age. The CMT typical phenotype in some was complicated by delayed motor development, sensorineural hearing loss, tremor, and pathological fractures. Axonal loss affected all patients. An X-linked dominant inheritance and carrier females with abnormal exam correlated with a connexin 32 mutation in all but 2 pedigrees. The clinical phenotype for CMTX1 is broader than previously recorded. [4]