Question 1

What genetic mutation causes Huntington disease?

Accepted Answer

Huntington disease results from expansion of CAG trinucleotide repeats in the HTT gene on chromosome 4. Normal alleles contain 26 or fewer repeats, but 40 or more repeats cause full disease expression. This abnormal repeat expansion produces a misfolded huntingtin protein with an expanded polyglutamine tract that disrupts cellular function and leads to neuronal death.

Question 2

How does genetic anticipation affect Huntington disease severity?

Accepted Answer

Genetic anticipation causes Huntington disease to become earlier in onset and more severe in successive generations, particularly with paternal inheritance. Juvenile-onset cases, occurring before age 20 and accounting for 5-10% of cases, progress more rapidly than adult-onset disease. This phenomenon reflects the tendency for CAG repeat expansions to increase when transmitted through generations.

Question 3

What motor symptoms characterize Huntington disease?

Accepted Answer

Huntington disease presents with involuntary jerky movements called chorea, slow writhing motions known as athetosis, and sustained muscle contractions called dystonia. Juvenile-onset cases often resemble Parkinsonism with bradykinesia, rigidity, and tremor. As disease progresses, voluntary motor control declines, causing slurred speech, difficulty swallowing, and poor coordination related to alterations in muscle tone.

Question 4

What cognitive and psychiatric symptoms develop in Huntington disease?

Accepted Answer

Cognitive symptoms progress from early deficits in executive function, attention, and processing speed to global dementia. Psychiatric features include depression, anxiety, obsessive-compulsive behaviors, apathy, irritability, and impulsivity, which may precede motor signs. These neuropsychiatric manifestations significantly impact quality of life and often require clinical management alongside motor symptoms.

Question 5

When does Huntington disease typically present and how long does it progress?

Accepted Answer

Huntington disease typically presents between ages 30 and 50, though juvenile cases occur before age 20 and progress more rapidly. The disease causes continuous neurological decline over 15-20 years, with death typically occurring within this timeframe of symptom onset. Advanced stages involve severe swallowing difficulty, weight loss, aspiration, and malnutrition.

Question 6

How does the abnormal huntingtin protein damage neurons in Huntington disease?

Accepted Answer

The expanded polyglutamine tract in the abnormal huntingtin protein causes the protein to misfold, disrupting normal cellular function. This misfolded protein accumulates in neurons, leading to cellular dysfunction and ultimately neuronal death. The progressive neuronal loss throughout the brain causes the characteristic motor, cognitive, and psychiatric decline observed in Huntington disease.

Question 7

What is the inheritance pattern of Huntington disease?

Accepted Answer

Huntington disease is inherited in an autosomal dominant pattern, meaning a single mutated HTT gene copy from either parent causes disease. Each child of an affected parent has a 50% chance of inheriting the mutation. The disease is progressive and fatal, with no cure currently available, making genetic counseling important for at-risk family members.

Choroba Huntingtona I: Wprowadzenie

Browse More Videos