Giant axonal neuropathy

Giant axonal neuropathy (GAN) is a rare, progressive, autosomal recessive neurodegenerative disorder. The disease is caused by variations in the gene GAN located on chromosome 16q24. The gene encodes gigaxonin, a protein involved in the dynamics of intermediate filaments and cytoskeletal framework. The defect in gigaxonin leads to an aberrant accumulation of neurofilaments within the axons leading to the development of progressive peripheral and central nervous system manifestations. Clinical features include a severe early-onset peripheral sensory motor neuropathy that might also involve the cranial nerves leading to facial weakness, optic atrophy and ophthalmoplegia. Patients generally present in early childhood with difficulty walking. By late teens, most are wheelchair bound with significant kyphoscoliosis. As the disorder worsens, the central nervous system is involved with intellectual disability, cerebellar ataxia, pyramidal signs and seizures. Visual and hearing disturbances may also develop. The nerves of the autonomic nervous system can become damaged by the accumulation of neurofilaments. Patients characteristically have tightly curled hair and a typical facial phenotype. Treatment is currently symptomatic and the average life expectancy is in the early twenties.