From the Guidelines
Huntington's disease is diagnosed based on a combination of clinical evaluation, genetic testing, and imaging studies, with the presence of more than 38 CAG repeats in the huntingtin gene being a key diagnostic criterion.
Diagnostic Criteria
The diagnostic criteria for Huntington's disease include:
- Genetic testing: The presence of more than 38 CAG repeats in the huntingtin gene on the short arm of chromosome 4 is used to confirm the diagnosis 1.
- Clinical evaluation: Patients with suspected HD should undergo a thorough clinical evaluation to assess for symptoms such as chorea, cognitive dysfunction, and psychiatric changes 1.
- Imaging studies: Imaging studies such as MRI may be used to support the diagnosis, although they may be normal early in the disease course 1.
Key Diagnostic Features
The key diagnostic features of Huntington's disease include:
- Autosomal dominant inheritance: HD is an autosomal dominant disorder, meaning that a single copy of the mutated gene is sufficient to cause the disease 1.
- CAG repeat expansion: The disease is caused by an expansion of a polymorphic trinucleotide (CAG) repeat in the huntingtin gene, with more than 38 repeats being diagnostic 1.
- Variable penetrance: There is variable penetrance for alleles carrying 36-39 repeats, but the disease appears fully penetrant when the repeat numbers are >40 1.
Laboratory Testing
Laboratory testing for HD involves measuring the length of the CAG repeat region of the HTT gene, with tests being >99% sensitive for detecting CAG repeat expansion mutations 1.
Clinical Considerations
In clinical practice, a diagnosis of HD should be considered in patients with symptoms such as chorea, cognitive dysfunction, and psychiatric changes, particularly if there is a family history of the disease 1. Genetic counseling and testing should be offered to patients with suspected HD, and imaging studies may be used to support the diagnosis 1.
From the Research
Diagnostic Criteria for Huntington's Disease
The diagnostic criteria for Huntington's disease (HD) involve a combination of clinical features and genetic testing. The diagnosis is usually confirmed through identification of an increased CAG repeat length in the huntingtin gene in a patient with clinical features of the condition 2.
Clinical Features
The clinical features of HD include:
- Neuropsychiatric symptoms
- A movement disorder, most commonly choreiform
- Progressive cognitive impairment 2
- Chorea, cognitive impairment, and psychiatric disorders 3
- Unwanted choreatic movements, behavioral and psychiatric disturbances, and dementia 4
- Progressive motor, cognitive, and psychiatric symptoms 5
Genetic Testing
Genetic testing for HD involves detection of the CAG repeat expansion in the Huntingtin (HTT) gene 6. There are three main types of HD genetic testing:
- Diagnostic testing to confirm or rule out disease
- Presymptomatic testing to determine whether an at-risk individual inherited the expanded allele
- Prenatal testing to determine whether the fetus has inherited the expanded allele 6
Diagnostic Confirmation
Diagnosis is based on clinical symptoms and signs in an individual with a parent with proven HD, and is confirmed by DNA determination 4. The diagnosis can be challenging, especially in cases of unusual presentations or when considering genetic testing in asymptomatic carriers 2.
Differential Diagnoses
Differential diagnoses include other causes of chorea, such as general internal disorders or iatrogenic disorders, as well as phenocopies (clinically diagnosed cases of HD without the genetic mutation) 4.