Clinical characteristics: Hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC), a neurodevelopmental and neurodegenerative disorder, is characterized by severe progressive sensorimotor neuropathy with resulting hypotonia, areflexia, and amyotrophy, and by variable degrees of dysgenesis of the corpus callosum. Mild-to-severe intellectual disability and "psychotic episodes" during adolescence are observed. Sensory modalities are moderately to severely affected beginning in infancy. The average age of onset of walking is 3.8 years; the average age of loss of walking is 13.8 years; the average age of death is 33 years.
Diagnosis/testing: The diagnosis of HMSN/ACC is established in a proband with suggestive findings and biallelic pathogenic variants in SLC12A6 identified by molecular genetic testing.
Management: Treatment of manifestations: Walking aids such as canes or walkers are required. As the disease progresses, orthoses for upper and lower limbs and physiotherapy are needed to prevent contractures. Early developmental/educational intervention addresses cognitive delays. Depending on severity, individuals with HMSN/ACC usually require corrective surgery for scoliosis. Neuroleptics may be used to treat psychiatric manifestations, usually during adolescence.
Surveillance: Monitor in the early teens for scoliosis and in the late teens for psychiatric manifestations.
Genetic counseling: HMSN/ACC is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Heterozygotes (carriers) are asymptomatic. Once the SLC12A6 pathogenic variants have been identified in an affected family member, carrier testing for at-risk family members and prenatal and preimplantation genetic testing are possible.
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