Huntington disease (HD) is a progressive autosomal dominant neurodegenerative disease usually with adult onset. Diagnosis is based on clinical presentation of which symptoms include involuntary movement, progressive dementia, and psychiatric disturbances. A trinucleotide CAG repeat expansion in the huntingtin gene is diagnostic of Huntington disease. The repeat is expanded on HD chromosomes and is diagnostic of HD. The normal range is up to 26 copies of the repeat, while the expanded range is 36 or more repeats. Age of onset shows an association with the length of the CAG repeat; however, genotype/phenotype correlations are not precise enough to be used clinically at the present time.

Reasons for Referral:

• Confirmation of diagnosis or clinical suspicion of HD in symptomatic patients
• Confirmation of juvenile HD in symptomatic minors (requires medical records accompany specimen)
• Predictive testing for asymptomatic individuals, 18 years or older, with a 50% risk for HD. For asymptomatic minors, see ASHG Points to Consider*
• Prenatal diagnosis for high risk families (contact lab for specific requirements)

We recommend that genetic and/or psychological counseling be made available to all patients considering having confirmatory testing for HD.

Protocol For Predictive Testing:

• Predictive testing for adult onset disease is available to individuals ages 18 and older at 50% risk.
• Subjects must be enrolled in a center with a written protocol for predictive testing.
• Molecular analysis of the clinically affected relative is recommended.
• A signed consent form from the predictive testing center must be submitted with the specimen.

Testing Methodology:

Direct Mutation Analysis: PCR analysis across the CAG region to determine allele sizes. Additional PCR assays are available for unusual or complex cases. All normal size alleles and the vast majority of expanded alleles will be detected in this analysis. Southern analysis is used to identify extremely large CAG expansions (>100 repeats). Allele-size ranges are subject to change as more information becomes available.

Specimen Requirements:

Blood: EDTA (purple-top) tubes: Adults: 14 cc; Child: 6 cc; Infant: 2-3 cc
Requisition form, HD Indication and reporting form and consent form must accompany specimen. For information about prenatal testing, contact our laboratory.