Hereditary chorea - what else to consider when the Huntington's disease genetics test is negative?

Area of Science:

• Neurology
• Genetics
• Movement Disorders

Background:

• Huntington's disease (HD) is characterized by chorea, cognitive decline, and behavioral changes, often with a positive family history.
• While HD is a common cause, several hereditary conditions can mimic its presentation, known as HD phenocopies.
• These phenocopies require consideration when genetic testing for HD is negative.

Purpose of the Study:

• To review the phenotypes and diagnostic approaches for Huntington's disease-like (HDL) disorders.
• To differentiate HDL conditions from classic HD when genetic testing is negative.
• To highlight the importance of molecular genetic testing in diagnosing heterogeneous hereditary choreas.

Main Methods:

• Systematic literature search of PubMed and Cochrane Database (1946-2016).
• Inclusion of search terms: 'chorea', 'Huntington's disease', 'HDL', and 'phenocopies'.
• Focus on progressive chorea with cognitive impairment in the absence of HD gene mutations.

Main Results:

• HD phenocopies often present with additional movement disorders like myoclonus, dystonia, parkinsonism, and tics.
• Molecular genetic testing is key to distinguishing various hereditary choreas from HD.
• While many HDL disorders are not curable, precise diagnosis aids patient and family understanding.

Conclusions:

• Accurate diagnosis of HD phenocopies is essential for appropriate patient management.
• Advances in molecular genetics facilitate the differentiation of HD from its mimics.
• Understanding the specific genetic basis of chorea improves patient counseling and care.