SNP Shot: Genomic Insights

Huntington's disease (HD) is a brain disorder that progressively impairs movement, emotions, and cognitive functions like thinking and reasoning.

The most prevalent form, adult-onset HD, typically manifests in a person's 30s or 40s. Initial symptoms may include irritability, depression, minor involuntary movements, poor coordination, and difficulty learning or making decisions. Many individuals with HD develop chorea, characterized by involuntary jerking or twitching. As the disease advances, these movements become more severe. Patients may experience difficulty walking, speaking, and swallowing. Personality changes and a decline in cognitive abilities are also common. Those with adult-onset HD generally survive for approximately 15 to 20 years following the appearance of initial symptoms.

A less common form, juvenile HD, begins during childhood or adolescence. It similarly involves movement problems along with mental and emotional changes. Other symptoms specific to juvenile HD include slowed movements, clumsiness, frequent falls, rigidity, slurred speech, and excessive drooling. Academic performance deteriorates as cognitive skills decline. Seizures occur in 30% to 50% of children affected. Juvenile HD tends to progress more rapidly than the adult-onset form, with affected individuals typically surviving 10 to 15 years after the onset of symptoms.

Inheritance:

HD follows an autosomal dominant inheritance pattern. This means that having only one copy of the mutated gene in each cell is enough to cause the disorder. Usually, an affected individual inherits the gene from one affected parent. Rarely, someone with HD has no family history of the disease. The HTT gene contains a repeating segment called a CAG trinucleotide repeat. The size of this repeat often expands as the altered HTT gene is passed down through generations. A larger number of repeats is typically linked to an earlier onset of signs and symptoms, a phenomenon called anticipation. People with adult-onset HD usually have 40 to 50 CAG repeats in the HTT gene, while those with juvenile HD tend to have more than 60. Individuals with 27 to 35 CAG repeats in the HTT gene will not develop HD themselves but face the risk of having children who will. When the gene passes from parent to child, the CAG repeat size may expand into the range (36 repeats or more) that causes Huntington's disease.