Huntington Disease - HD

  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

  • Diagnostic confirmation in symptomatic individual (eg, chorea, cognitive defects, tremor)
  • Presymptomatic testing for adults with a family history of Huntington disease (HD)

Laboratory Testing

  • DNA testing of asymptomatic individuals should also involve neurological and psychological examination in addition to genetic counseling and proper informed consent

Differential Diagnosis

Huntington disease (HD) is a progressive, hereditary, neurodegenerative disorder.


  • Incidence – 1/15,000 in Western Europe
    • Much lower prevalence in Japan
  • Age – typically onset is 35-44 years
    • Juvenile onset (<21 years) –  ~5% of cases


  • Autosomal dominant
  • >99% of cases result from an expanded number of cytosine-adenine-guanine (CAG) repeats in exon 1 of the Huntington gene (HD)
  • Encoded protein, huntingtin – expressed in neural and non-neural tissues
    • Mutant protein – suspected to cause neuronal loss in selective areas of the cortex, striatum and extrastriatal structures
  • Allele sizes are classified by the number of CAG repeats
    • Normal
      • ≤26 CAG repeats
      • Not at risk for developing or transmitting HD
    • Mutable normal
      • 27-35 CAG repeats
      • Unaffected; males have 2.5% risk for CAG expansion in offspring to disease-causing range
      • ~1-2% of the general population carry an allele of this size
    • Reduced penetrance
      • 36-39 CAG repeats
      • At risk for developing symptoms of HD
      • Offspring also at risk for HD
    • Full penetrance
      • ≥40 CAG repeats
      • Disease causing
      • Offspring at 50% risk for developing HD
  • Higher numbers of CAG repeat lengths are associated with earlier disease onset
    • Not possible to predict the specific age of onset, severity, symptoms, and rate of disease progression from number of CAG repeats
  • Most individuals with HD have an affected parent
    • Apparent de novo cases may be explained by the death of a parent before symptom onset, unrecognized diagnosis in family, intermediate or reduced penetrance allele resulting in absent or late-onset symptoms in a parent, or non-paternity
  • Allele sizes may increase during paternal transmission (genetic anticipation) – results in earlier onset in the offspring of an affected male

Clinical Presentation

  • Progressive neurodegenerative disorder
    • Motor symptoms
      • Tremor
      • Chorea/choreoathetosis
      • Slow ocular saccades
      • Akinesia, bradykinesia
      • Dystonia
    • Cognitive symptoms
      • Cognitive speed impaired first (executive function)
      • Mood disorders
      • Suicidal ideation
      • Dementia
    • Relentless progression of disease with death 15-20 years after onset
    • Successive generations tend to have earlier onset
  • Juvenile onset symptoms
    • Clumsiness
    • Hyperreflexia
    • Occulomotor disturbances
    • Physical instability/falls
    • Rigidity
    • Mental deterioration
    • Seizure disorder
    • Rapid decline
Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Huntington Disease (HD) Mutation by PCR 0040018
Method: Polymerase Chain Reaction/Fragment Analysis


Test is NOT performed on minors <18 years 

Prenatal testing is NOT performed

HD mutations other than cytosine-adenine-guanine (CAG) expansions are not detected

Neurodegenerative conditions unrelated to HD are not detected


If only one allele is detected by PCR, Southern blot is performed to determine if there is a second allele with an expanded CAG repeat

General References

Gövert F, Schneider SA. Huntington's disease and Huntington's disease-like syndromes: an overview. Curr Opin Neurol. 2013; 26(4): 420-7. PubMed

Huntington's Disease Society of America (HDSA). [Accessed: Feb 2017]

Imarisio S, Carmichael J, Korolchuk V, Chen C, Saiki S, Rose C, Krishna G, Davies JE, Ttofi E, Underwood BR, Rubinsztein DC. Huntington's disease: from pathology and genetics to potential therapies. Biochem J. 2008; 412(2): 191-209. PubMed

Novak MJ, Tabrizi SJ. Huntington's disease: clinical presentation and treatment. Int Rev Neurobiol. 2011; 98: 297-323. PubMed

Roos RA. Huntington's disease: a clinical review. Orphanet J Rare Dis. 2010; 5: 40. PubMed

Shannon KM. Huntington's disease - clinical signs, symptoms, presymptomatic diagnosis, and diagnosis. Handb Clin Neurol. 2011; 100: 3-13. PubMed

Tibben A. Predictive testing for Huntington's disease. Brain Res Bull. 2007; 72(2-3): 165-71. PubMed

Walker FO. Huntington's disease. Lancet. 2007; 369(9557): 218-28. PubMed

Medical Reviewers

Last Update: March 2017