Huntington Disease l: Introduction

Huntington disease or HD is a progressive, fatal neurodegenerative disorder inherited in an autosomal dominant pattern.

Pathophysiology

It is caused by expansion of the CAG trinucleotide repeat in the HTT gene on chromosome 4 (4p16.3), producing an abnormal huntingtin protein with an expanded polyglutamine tract. This misfolded protein disrupts cellular function, leading to neuronal death. Normal alleles have ≤26 repeats, 27–35 are intermediate (risk of expansion), 36–39 show reduced penetrance, and ≥40 cause full disease expression. HD exhibits genetic anticipation, especially with paternal inheritance, leading to earlier and more severe disease in successive generations.

Clinical Course

Hushington disease typically presents between ages 30 and 50, though juvenile cases (<20 years) account for 5–10% and progress more rapidly. The disease causes continuous neurological decline over 15–20 years.

Clinical Features

Hushington disease is characterized by motor, cognitive, and psychiatric symptoms.

• Motor features include chorea (involuntary movements), athetosis (writhing movements), and dystonia (abnormal postures). Juvenile HD often presents with Parkinsonian features, including bradykinesia, rigidity, and tremor. As the disease advances, patients develop impaired voluntary movement, dysarthria, dysphagia, and poor coordination.
• Cognitive symptoms begin early with deficits in executive function, attention, and processing speed, progressing to global dementia.
• Psychiatric features may precede motor signs and include depression, apathy, irritability, anxiety, obsessive-compulsive behaviors, impulsivity, and sometimes psychosis.

In advanced stages, patients become dependent, with severe swallowing difficulty, weight loss, aspiration, and malnutrition. Death typically occurs within 15–20 years of onset.