SNP Shot: Genomic Insights

Giant axonal neuropathy (GAN) is a genetic disorder distinguished by the presence of unusually large and malfunctioning nerve fibers called giant axons. Axons are vital components of nerve cells (neurons), serving as pathways for the transmission of nerve signals. The initial symptoms often manifest in the peripheral nervous system, where extended axons link the brain and spinal cord (the central nervous system) to muscles and sensory receptors responsible for detecting sensations like touch, pain, temperature, and sound. Ultimately, axons within the central nervous system also become involved.

Typically, the symptoms of GAN emerge in early childhood and progressively worsen. A common initial sign is difficulty walking. Subsequently, individuals may experience a decline in sensation, muscle strength, and reflexes in their extremities. They may also develop problems with coordination (ataxia) and eventually require wheelchair assistance. Scoliosis, an abnormal spinal curvature, is frequently observed. Visual and auditory impairments are also possible. A notable feature in many affected individuals is unusually kinky hair, significantly different from other family members.

GAN can also affect the autonomic nervous system, which regulates involuntary bodily functions. This can lead to complications such as constipation, sensitivity to heat, urinary dysfunction (neurogenic bladder), and a decrease or complete loss of the ability to sweat.

As GAN progresses, more severe issues can arise, including paralysis, seizures, difficulty with breathing or swallowing, and a gradual deterioration of cognitive abilities (dementia). Sadly, most individuals with GAN do not live beyond their twenties.

A less severe presentation of GAN exists, with symptoms appearing later in life. In these cases, movement difficulties are less pronounced, and the condition typically progresses more slowly than the classic form. These individuals often have straight hair and may live into adulthood.

Inheritance:

GAN follows an autosomal recessive inheritance pattern. This means that both copies of the responsible gene in each cell must carry mutations for the condition to develop. Individuals with GAN inherit one mutated gene copy from each parent, who are carriers but usually do not exhibit any signs or symptoms of the disorder themselves.