Giant axonal neuropathy

Giant axonal neuropathy (GAN) is a rare autosomal recessive disorder characterized by the disorganization of neurofilaments, structural elements crucial for neuron shape and function. A distinctive feature is the presence of kinky or curly hair, leading to the alternate name GAN with curly hair.

Signs and symptoms typically emerge in infancy or early childhood and include low muscle tone (hypotonia), muscle weakness, decreased reflexes, impaired coordination (ataxia), seizures, and intellectual disability. The disorder progresses, affecting both the peripheral and central nervous systems, often resulting in sensory issues, mobility problems, and a gradual decline in mental function.

GAN arises from mutations in the GAN gene, which encodes the gigaxonin protein. These mutations disrupt protein interactions necessary for neuron structural organization, causing axons to accumulate excess neurofilaments. This leads to axonal enlargement and dysfunction, impairing nerve signal transmission and eventually resulting in neuronal deterioration.

As an autosomal recessive disorder, both parents must carry at least one copy of the defective gene to pass it on to their child. Affected individuals experience a range of neurological issues, with abnormally kinky hair being a nearly universal characteristic. Early signs often involve peripheral nervous system dysfunction, followed by central nervous system involvement as the disease progresses.