Huntington Disease —

Clinical Correlations and Patient Presentation

Lectures 31-32

Lecture will be followed by case presentation

December 7 (Friday), 2001

Required Reading: Principles of Medical Genetics

Gelerhter TD, Collins FS, Ginsburg D

1998 Williams and Wilkins

Pages: review 217-220

This Handout!

  • Know the basic inheritance pattern and symptoms of Huntington disease:

  • It is an autosomal dominant disorder with high penetrance.

  • It is a neurodegenerative disorder that most often progresses over a 10-25 years

  • Symptoms generally appear between 30-50 years of age, but have appeared as old as 90 and as young as two years of age.

  • Symptoms include:

- Involuntary choreiform movements.

- Ataxic gait.

- Psychiatric symptoms including depression, mood swings.

- Swallowing difficulties (dysphasia).

- Speech difficulties (dysarthria).

  • Approximately 1 in 10,000 individuals will develop HD -- currently over 30,000 individuals have the disease and over 150,000 individuals are at risk of inheriting the disorder in the United States alone.

  • It affects all races and ethnic groups.

  • Understand the basic genetic etiology and genetic abnormality:

  • The gene was mapped to 4p in 1983 and cloned in 1993.

  • The HD gene contains a CAG trinucleotide repeat:

- Normal individuals have 10-33 copies of this repeat on both HD alleles.

- Affected individuals generally have over 39 copies of the repeat on one allele.

- Individuals with 34-39 copies fall into an intermediate "gray zone."

- All individuals who inherit a clearly expanded allele from one parent will eventually develop the disease if they live long enough.

  • The specific pathophysiology is poorly understood, but autopsy study of affected individuals’ brains show atrophy, especially of the caudate nucleus.

 

  • Know that PCR-based DNA testing can be done to confirm a diagnosis or "presymptomatically." Understand the interpretation of a DNA test for HD. Know that this test cannot predict the age of onset or exact course or progression of symptoms.

  • Know the Huntington Disease Society of America recommendations for the process of presymptomatic HD testing which include:

  • Genetic counseling.

  • Neurological evaluation.

  • Psychological evaluation.

  • Presence of a support person.

  • Identification of a local counselor.

  • Results disclosure in person.

  • Minors tested only if clinically indicated.

 

Understand that at-risk individuals, even within the same families, may have different motivations and desires to undergo or not undergo testing. Each person must be treated individually and give informed consent to undergo testing. Although testing other family members is not required, especially for those asymptomatic or presymptomatic individuals, it is often useful to confirm the diagnosis of the disease in an affected family member by DNA testing as other neurological disorders may mimic HD.