Giant axonal neuropathy (GAN) is characterized by a severe early-onset peripheral motor and sensory neuropathy, central nervous system involvement (intellectual disability, seizures, cerebellar signs, and pyramidal tract signs), and characteristic tightly curled hair. Most individuals become wheelchair dependent in the second decade of life and eventually bedridden with severe polyneuropathy, ataxia, and dementia. Death usually occurs in the third decade.
The diagnosis of GAN is established by clinical findings including nerve conduction velocity (NCV), brain MRI, and peripheral nerve biopsy. The pathologic hallmark is so-called giant axons caused by the accumulation of neurofilaments. GAN is caused by mutations in GAN, encoding the protein gigaxonin. GAN is the only gene in which mutation is currently known to be associated with GAN; however, evidence exists for genetic heterogeneity. Molecular genetic testing of GAN is available.
GAN 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. Once an at-risk individual is known to be unaffected, the chance of his/her being a carrier is 2/3. Individuals with GAN usually do not reproduce. Prenatal testing may be available through laboratories offering custom prenatal testing if the disease-causing mutations in a family are known.