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Huntington Disease-Like 2.

Authors

Margolis RL1.

Source

GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
2004 Jan 30 [updated 2012 Apr 26].

Author information

1
Professor of Psychiatry and Neurology, Laboratory of Genetic Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland

Excerpt

CLINICAL CHARACTERISTICS:

Huntington disease-like 2 (HDL2) typically presents in midlife with a relentless progressive triad of movement, emotional, and cognitive abnormalities progressing to death over ten to 20 years. In some individuals the presentation resembles juvenile-onset Huntington disease (HD) or the Westphal variant of HD, usually presenting in the fourth decade (ages 29 to 41 years) with diminished coordination and weight loss despite increase in food intake. Neurologic abnormalities include parkinsonism (rigidity, bradykinesia, tremor), dysarthria, and hyperreflexia. In others the presentation is more variable but, in general, corresponds to typical HD.

DIAGNOSIS/TESTING:

The diagnosis of HDL2 requires molecular genetic testing of JPH3, the only gene in which mutation is known to cause HDL2. In the presence of a clinical syndrome consistent with HDL2 (findings and family history typical of Huntington disease), 41 or more CTG trinucleotide repeats in JPH3 are considered diagnostic of HDL2.

MANAGEMENT:

Treatment of manifestations: Treatment is symptomatic and is presumably similar to that for HD and other neurodegenerative disorders, though this must be considered speculative pending objective data. Pharmacologic agents that may suppress abnormal movements include low-dose neuroleptic agents such as fluphenazine and haloperidol, and potentially tetrabenazine. Antidepressants, antipsychotics, mood stabilizers (lithium, valproic acid, carbamazepine, and lamotragine), and occasionally stimulants may treat psychiatric manifestations. Education about the course of disease and environmental interventions (regular schedules, use of lists to assist memory, removing clutter so that things are easier to find) benefit affected individuals and family members. Prevention of secondary complications: Remove loose rugs and clutter from the individual's home to help prevent falls and other injuries; driving may need to be curtailed or limited to prevent risk of accidents; food should be prepared in such a manner as to prevent choking. Surveillance: Monitor nutrition and swallowing in order to implement feeding changes when necessary to minimize risk of aspiration; gait should be monitored, with use of appropriate strategies or devices to minimize falls; monitor driving to assure that the affected individual does not present a danger to themselves or others; monitor mood and irritability, such that measures to decrease the risk of suicide, other behavioral abnormalities, and distress may be implemented. Agents/circumstances to avoid: Any agents that increase ataxia should be used with caution; avoid polypharmacy, which may exacerbate delirium.

GENETIC COUNSELING:

HDL2 is inherited in an autosomal dominant manner. HDL2 resulting from a de novo pathogenic variant has not been reported. If a parent of the proband is affected or has the JPH3 expansion, the risk to each sib of a proband is 50%. Prenatal testing for pregnancies at increased risk is possible if the pathogenic variant in the family has been identified.

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