Giant Axonal Neuropathy (GAN)

Description

Giant Axonal Neuropathy (GAN) is a rare, inherited neurological disorder that affects the peripheral nervous system. This condition causes progressive nerve damage, leading to a wide range of symptoms, including muscle weakness, sensory impairments, and even cognitive difficulties. While there is currently no cure for GAN, understanding its causes, diagnosis, and management options can empower individuals to live fulfilling lives despite the challenges it presents.

Genes Involved

GAN is caused by mutations in the GAN gene, which provides instructions for producing a protein called gigaxonin. Gigaxonin is crucial for the proper formation and maintenance of the cytoskeleton, a network of fibers within cells that provides structural support. Mutations in the GAN gene disrupt gigaxonin function, leading to the accumulation of abnormal protein aggregates in nerve cells, ultimately causing nerve damage.

Recognizing the Signs and Symptoms

GAN symptoms typically emerge in childhood or adolescence, though they can sometimes appear later in life. The severity and progression of symptoms can vary greatly among individuals. Common signs and symptoms include:

Muscle weakness and atrophy: Particularly in the legs and feet, leading to difficulty walking and balance issues.
Sensory impairments: Numbness, tingling, or pain in the extremities, often described as a ‘stocking and glove‘ distribution.
Delayed reflexes: A slower response to stimuli, especially in the limbs.
Vision problems: Optic atrophy, leading to blurred vision, color blindness, or even blindness in severe cases.
Cognitive difficulties: Learning disabilities, speech delays, and behavioral issues may occur in some individuals.
Other symptoms: Seizures, hearing loss, and gastrointestinal problems may also be present in some cases.

Causes

GAN is an autosomal recessive disorder, meaning that an individual must inherit two copies of the mutated GAN gene, one from each parent, to develop the condition. Parents who carry one copy of the mutated gene are considered carriers but do not typically experience symptoms themselves.

Inheritance/recurrence risk

Inheritance or Recurrence Risk

If both parents are carriers of the mutated GAN gene, there is a 25% chance that each of their children will inherit two copies of the mutated gene and develop GAN. There is also a 50% chance that each child will inherit one copy of the mutated gene and become a carrier. The remaining 25% chance is that a child will inherit two normal copies of the gene and not be affected by GAN.

WES Whole Exome Sequencing