From the Guidelines
Diagnosing Huntington's disease (Huntington's chorea) requires a combination of clinical evaluation, family history assessment, and genetic testing, with the most definitive diagnostic method being a genetic test that identifies the expanded CAG repeat in the HTT gene on chromosome 4, as stated in the 2020 study by the Journal of the American College of Radiology 1. The diagnostic criteria for Huntington's disease involve a thorough neurological examination to identify characteristic symptoms such as involuntary movements (chorea), cognitive decline, and psychiatric disturbances.
- A detailed family history is also crucial since Huntington's disease is an autosomal dominant disorder, meaning a person with an affected parent has a 50% chance of inheriting the disease.
- Neuroimaging studies like MRI or CT scans may show characteristic brain changes, particularly atrophy of the caudate nucleus and putamen, which can support the diagnosis.
- Genetic testing to determine the CAG repeat number for each allele is commercially available and the diagnostic test of choice, as mentioned in the 2020 study by the Journal of the American College of Radiology 1.
- The genetic test is nearly 100% accurate and can confirm the diagnosis even before symptoms appear, though predictive testing in asymptomatic individuals requires careful ethical consideration and psychological support. The 2014 study by the American College of Medical Genetics and Genomics 1 provides a brief clinical description of Huntington's disease, highlighting its neurodegenerative nature and the importance of genetic testing in diagnosis.
- The study also mentions the prevalence of Huntington's disease, which affects ~3–5 out of 100,000 individuals, with a higher prevalence in some populations of western European origin.
- The 1998 study by the American College of Medical Genetics/American Society of Human Genetics Huntington Disease Genetic Testing Working Group 1 discusses the standardization and interpretation of IT-15 gene (CAG)n repeat ranges, which is essential for accurate diagnosis. However, the most recent and highest quality study, the 2020 study by the Journal of the American College of Radiology 1, takes precedence in guiding the diagnostic criteria for Huntington's disease. Therefore, the diagnostic criteria for Huntington's disease should prioritize genetic testing, clinical evaluation, and family history assessment, with careful consideration of the psychological implications of a positive diagnosis, as recommended by the 2020 study 1.
From the Research
Diagnostic Criteria for Huntington's Chorea
The diagnostic criteria for Huntington's chorea, also known as Huntington's disease (HD), include:
- Clinical symptoms and signs in an individual with a parent with proven HD 2
- Identification of an increased CAG repeat length in the huntingtin gene in a patient with clinical features of the condition 3
- Characterized by the progressive deterioration of GABAergic neurons in the basal ganglia, subcortical-type dementia, behavioral abnormalities, midlife psychosis, and gradual inadvertent choreoathetosis movements 4
- Atrophy of the dorsal striatum (caudate nucleus and putamen) with concurrent expansion of the frontal horns of the lateral ventricles on imaging modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) 4
Clinical Features
The clinical features of HD include:
- Unwanted choreatic movements, behavioral and psychiatric disturbances, and dementia 2
- Chorea that gradually spreads to all muscles, severely retarding all psychomotor processes 2
- Psychiatric symptoms and cognitive decline 2
- Neuropsychiatric symptoms, a movement disorder (most commonly choreiform), and progressive cognitive impairment 3
Genetic Diagnosis
Genetic diagnosis of HD is based on:
- Identification of an elongated CAG repeat (36 repeats or more) on the short arm of chromosome 4p16.3 in the Huntingtine gene 2
- DNA determination to confirm the diagnosis in individuals with clinical symptoms and a family history of HD 2
- Predictive testing available to those at risk, but only experienced clinicians should perform the counseling and testing 5, 6