From the Guidelines
Sporadic Huntington disease is extremely rare and typically results from new mutations in the HTT gene, requiring genetic testing to confirm the CAG trinucleotide repeat expansion in the HTT gene, typically showing 40 or more repeats, as the diagnostic test of choice 1. The diagnosis of sporadic Huntington disease involves a comprehensive workup to rule out other potential etiologies of chorea, including genetic and neurodegenerative disorders, as well as acquired conditions such as cerebrovascular, infectious, autoimmune, metabolic, neurodegenerative, and drug-induced syndromes 1. Key features of the disease include:
- Progressive motor dysfunction, including chorea and dystonia
- Cognitive decline
- Psychiatric disturbances Management of sporadic Huntington disease is symptomatic and supportive, and may include:
- Medications like tetrabenazine or deutetrabenazine for chorea
- Antipsychotics for behavioral symptoms
- Antidepressants for mood disorders
- Physical therapy, occupational therapy, and speech therapy to maintain functional abilities Genetic counseling is still important for sporadic cases, as the mutation can be passed to offspring, and patients with suspected HD should undergo genetic counseling and testing to exclude or confirm HD in concert with initial imaging 1. The disease progresses over 10-30 years, eventually requiring full-time care, with death usually resulting from complications like pneumonia or heart failure.
From the Research
Definition and Prevalence of Huntington Disease
- Huntington disease (HD) is a rare neurodegenerative disorder of the central nervous system characterized by unwanted choreatic movements, behavioral and psychiatric disturbances, and dementia 2.
- The prevalence of HD in the Caucasian population is estimated at 1/10,000-1/20,000 2.
- The mean age at onset of symptoms is 30-50 years, but symptoms can start before the age of 20 years, known as Juvenile Huntington's disease (JHD) 2.
Clinical Features and Diagnosis
- The classic sign of HD is chorea that gradually spreads to all muscles, and all psychomotor processes become severely retarded 2.
- Patients experience psychiatric symptoms and cognitive decline 2.
- Diagnosis is based on clinical symptoms and signs in an individual with a parent with proven HD, and is confirmed by DNA determination 2.
- Differential diagnoses include other causes of chorea, including general internal disorders or iatrogenic disorders 2.
Treatment and Management
- Tetrabenazine is a dopamine-depleting agent that may be effective in reducing chorea, although it has a risk of potentially serious adverse effects 3, 4, 5.
- The most common reasons for stopping upward titration of tetrabenazine are optimal chorea control, intolerability of higher doses, and reaching the maximum recommended dosage despite suboptimal chorea control 6.
- Chorea severity and non-persistence to tetrabenazine are associated with increased emergency room visits, hospitalizations, and days hospitalized 6.
- Management should be multidisciplinary and is based on treating symptoms with a view to improving quality of life 2.
Sporadic Huntington Disease
- There is no specific information available on sporadic Huntington disease in the provided studies.
- However, it is known that HD is an autosomal dominant inherited disease caused by an elongated CAG repeat on the short arm of chromosome 4p16.3 in the Huntingtine gene 2.
- Phenocopies (clinically diagnosed cases of HD without the genetic mutation) are observed, which may be relevant to sporadic cases 2.