and Patient Presentation
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
- Know the basic inheritance pattern
and symptoms of Huntington disease:
- It is an autosomal dominant disorder with
- 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
- Symptoms include:
Involuntary choreiform movements.
- Ataxic gait.
- Psychiatric symptoms
including depression, mood swings.
- Swallowing difficulties
- Speech difficulties
- 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
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
- 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