From the Guidelines
Huntington's disease diagnosis is primarily confirmed through genetic testing that identifies an expansion of CAG repeats in the HTT gene, with 40 or more repeats confirming the disease. This approach is supported by the most recent guidelines, including those from the American College of Radiology 1, which emphasize the importance of genetic testing in diagnosing Huntington's disease.
Clinical Evaluation and Family History
Before genetic testing, a thorough clinical evaluation and family history assessment are crucial. A neurologist will typically perform a detailed neurological examination looking for characteristic symptoms such as chorea (involuntary movements), cognitive decline, and psychiatric disturbances. A thorough family history is essential since Huntington's disease is inherited in an autosomal dominant pattern, meaning each child of an affected parent has a 50% chance of inheriting the mutation.
Genetic Testing
Genetic testing to determine the CAG repeat number for each allele is commercially available and the diagnostic test of choice 1. Patients with suspected HD should undergo genetic counseling and testing to exclude or confirm HD. It's also important to consider alternative diagnoses, as HD phenocopies can represent about 3% of patients referred for molecular confirmation of a clinical diagnosis of HD, and other loci (HDL1 and HDL2) have been identified 1.
Brain Imaging
Brain imaging studies like MRI or CT scans may support the diagnosis by showing characteristic atrophy of the caudate nucleus and putamen. However, imaging may be normal early on in the disease course, highlighting the importance of genetic testing in conjunction with clinical evaluation and family history assessment.
Predictive Testing and Management
Predictive genetic testing is available for asymptomatic individuals with a family history, but should always be accompanied by genetic counseling due to the profound implications of a positive result. The disease has no cure, so diagnosis focuses on confirming the genetic mutation and developing appropriate management strategies for symptoms as they develop.
Key points to consider in the diagnosis of Huntington's disease include:
- Genetic testing for CAG repeat expansion in the HTT gene
- Thorough clinical evaluation and family history assessment
- Consideration of alternative diagnoses
- The role of brain imaging in supporting the diagnosis
- The importance of genetic counseling for predictive testing and management of the disease.
From the Research
Diagnosis of Huntington's Disease
- Huntington's disease (HD) is diagnosed based on clinical symptoms and signs in an individual with a parent with proven HD, and is confirmed by DNA determination 2.
- 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 3.
- Diagnostic criteria for HD should be adapted to better reflect the natural history of the disease, including subtle motor dysfunction, cognitive changes, and behavioral alterations that often occur before diagnosis 4.
- HD can be divided into categories such as "genetically confirmed" with subcategories "presymptomatic," "prodromal," and "manifest" and "not genetically confirmed" subdivided into "clinically at risk," "clinically prodromal," and "clinically manifest" 4.
Diagnostic Challenges
- Unusual presentations of HD can occur, making diagnosis difficult 3.
- A growing number of conditions can mimic HD, including rare genetic causes, which must be considered in the event of a negative HD genetic test 3.
- Patients are best managed in specialist multidisciplinary clinics, including when considering genetic testing 3.
Diagnostic Tools
- DNA determination is used to confirm the diagnosis of HD 2.
- The Unified Huntington's Disease Rating Scale, including the Diagnostic Confidence Level and the Total Functional Capacity scales, can be used to assess the severity of HD 4.
- Chorionic villus sampling or amniocentesis can be used for prenatal diagnosis of HD 2.
- Preimplantation diagnosis with in vitro fertilization is offered in several countries for families with a history of HD 2.