The epidemiological, clinical, and molecular genetic aspects of hereditary motor and sensory neuropathy and agenesis of the corpus callosum (HMSN/ACC) are reviewed by neurologists at McGill University, Montreal, Canada. Rarely reported worldwide, HMSN/ACC is prevalent in the Saguenay-Lac-St-Jean region of Quebec, Canada. In this area, the incidence at birth is 1 in 2,117 live births and the carrier rate is 1 in 23 inhabitants. A set of 22 founders originating from France was common to all of the cases. First described in 1966 (LeBlanc et al), the autosomal recessive inheritance was recognized in 1972 (Andermann et al). The clinical manifestations have an early onset with delay in developmental milestones, a severe sensory-motor polyneuropathy with areflexia, agenesis of the corpus callosum, amyotrophy, hypotonia, cognitive impairment, and psychoses. The average age of walking is 3.8 years, scoliosis appears at age 10.4 years, the ability to walk is lost by 13.8 years, and the average age of death is 24.8 years (33 years in a more recent unpublished study by the authors). The gene defect is a mutation in SLC12A6, which codes for the cotransporter protein KCC3. [1]

COMMENT. HMSN/ACC is rare but is considered of interest because the SLC12A6 gene defect is causing both developmental (callosal agenesis) and degenerative abnormalities (progressive neuropathy, cognitive deficits, and psychoses) of central and peripheral nervous systems.