Knowledge on rare diseases and orphan drugs

Exact prevalence of the juvenile form is not known, but is estimated to be about 1/166,000. JHD is reported in 6% of the total cases of HD, which has a prevalence of 1/10,000.

Behavioral disturbances and learning difficulties at school are often the first signs. Motor behavior is often hypokinetic and bradykinetic with dystonic components. Dementia is present in the early stage of the disease. Chorea, the classical sign of HD, is rarely seen in the 1st decade and only appears in the 2nd decade. Seizures, ataxia and weight loss are common.

HD is caused by an elongated CAG repeat (36 repeats or more) on the short arm of chromosome 4 (4p16.3) in the huntingtin gene, HTT. In juvenile Huntington disease, the CAG repeat length is over 55 in most cases. The length of the repeat determines about 70% of the variance in age at onset but gives no indication of initial symptoms, course, or duration of illness. In 75% of patients with JHD, the father is the affected parent.

Diagnosis is based on clinical manifestations in an individual with a parent with proven HD, and is confirmed by DNA testing. Premanifest testing has been codified in the Guidelines of the International Huntington Association (IHA) and the World Federation of Neurology (WFN) Research Group, and is not performed in at-risk patients below the age of 18.

Differential diagnoses of JHD are young-onset type 2 spinocerebellar ataxia (SCA2: 12q) with chorea, dystonia, and dementia, and dentatorubral pallidoluysian atrophy (DRPLA: 12p) with chorea and myoclonic epilepsy, but also SCA3 (14q) with rigidity, ataxia, and dystonia and SCA17 (6q) with psychiatric features and dementia. Other causes of chorea including general internal disorders or iatrogenic drug-induced disorders must also be considered. Sydenham chorea and post-streptococcal chorea are is still present in many parts of the world.

No cure is currently available. Management should be multidisciplinary and is based on treating manifestations with a view to improving quality of life. Chorea should be treated with dopamine receptor blocking (risperidone, tiapride, pimozide) or depleting agents (tetrabenazine). None of these drugs are officially approved for use in children but are prescribed off-label as treatment of the main symptoms of the disease. Attempts have been made to treat hypokinesia with a number of antiparkinsonian drugs, but without success. Paramedical care with speech, occupational, and physical therapy with psychological support for the patient and family are recommended.

The progression of the disease leads to complete dependency in daily life, which results in patients requiring full-time care, and finally death. The mean disease duration is comparable or slightly shorter than adult HD. The most common cause of death is pneumonia.

Last update: April 2011 - Expert reviewer(s): Pr R.A.C. [Raymund] ROOS