SNP Shot: Genomic Insights

Ataxia neuropathy spectrum is a type of POLG-related disorder, a collection of conditions sharing similar symptoms that affect muscles, nerves, and the brain. This spectrum now encompasses what were previously known as mitochondrial recessive ataxia syndrome (MIRAS) and sensory ataxia neuropathy dysarthria and ophthalmoplegia (SANDO).

Individuals with ataxia neuropathy spectrum characteristically experience issues with coordination and balance (ataxia) and nerve problems (neuropathy). This neuropathy can be sensory, affecting sensations; motor, affecting movement; or mixed, affecting both. Sensory neuropathy leads to numbness, tingling, or pain in the limbs, while motor neuropathy affects nerves controlling muscle movement.

Encephalopathy, indicating significant brain dysfunction, and seizures are also common in individuals with ataxia neuropathy spectrum. Some may also exhibit ophthalmoplegia, causing weakness in eye muscles and leading to ptosis, or drooping eyelids. Additional symptoms can include involuntary muscle twitching (myoclonus), liver problems, depression, migraine headaches, and vision loss.

Inheritance:

The inheritance pattern of ataxia neuropathy spectrum varies depending on the gene involved. Mutations in the POLG gene result in an autosomal recessive form, requiring both copies of the gene in each cell to be mutated for the condition to manifest. In this case, both parents are carriers, each possessing one mutated copy of the gene, but typically do not exhibit symptoms themselves. Conversely, mutations in the TWNK gene lead to an autosomal dominant form, where only one altered copy of the gene in each cell is enough to cause the disorder.