What Is GAN-1?
GAN-1 is a type of CMT caused by autosomal recessive mutations in the GAN gene. This gene provides instructions for making gigaxonin, a protein that regulates the organization and turnover of the neurofilament network that gives nerve axons their structure. Mutations in the GAN gene disrupt this function, leading to impaired nerve signal transmission.
GAN-1 is autosomal recessive, meaning that both copies of the gene must have a mutation to cause this subtype.
Clinical Features
Symptoms of GAN-1 typically begin in early childhood and affect both the peripheral and central nervous systems. The disease is defined by the formation of abnormally enlarged nerve axons swollen with disorganized neurofilaments. Nerve conduction studies reflect a severe axonal process.
GAN-1 symptoms may include:
- Tightly curled, kinky hair that differs from the parents
- Progressive weakness and muscle atrophy of the limbs
- Reduced sensation in the hands and feet
- Reduced or absent reflexes
- Difficulty walking and coordination problems
- Central nervous system involvement, which may include seizures and cognitive impairment
- Foot drop
- Additional symptoms not listed here
Disease Course
GAN-1 is a severe, progressive disease of childhood onset. Both the peripheral and central nervous systems are affected, and most individuals lose the ability to walk during childhood or adolescence. The disease course is serious, with progression continuing over time.
