Choreatic movement disorders (without repeat expansion analysis)

Huntington’s disease (HD) phenocopies comprise a heterogeneous group of disorders that clinically mimic HD but occur in the absence of a pathogenic CAG-Repeat-Expansion in HTT gene, accounting for approximately 1% of patients with an HD-like phenotype. Hereditary disease entities presenting with chorea or featuring choreiform movements can be caused by monogenic repeat-expansion disorders like e.g. several ,  and pathogenic variants in a variety of genes. Clinical presentation is highly heterogeneous and includes both predominantly nonsyndromic forms with relatively isolated chorea and syndromic forms with broader multisystem involvement. Accompanying features may include cognitive decline, psychiatric symptoms, ataxia, polyneuropathy, acanthocytosis, cutaneous or scleral telangiectasias or characteristic MRI findings such as iron-related basal ganglia signal change.

Given the extensive genetic heterogeneity and rarity of the underlying disorders, the overall prevalence of choreiform movement disorders remains unknown.

A number of genes have been associated with choreic movement disorders. The genetic forms can be grouped into nonsyndromic and syndromic chorea. To date, approximately 100 genes have been implicated in childhood-onset chorea. While many of these genetic disorders are associated with severe phenotypes and reduced survival, resulting in death before adulthood, atypical presentations with adult-onset movement disorders have increasingly been reported, thereby expanding the recognized phenotypic spectrum of these conditions.

The genetic conditions associated with choreic movement disorders follow heterogeneous inheritance patterns.

• Where choreic movement disorders are suspected to have a genetic cause, molecular genetic testing can identify the underlying condition and confirm a clinical suspicion.
• The identified entity guides further clinical management and is a prerequisite for targeted medical care; therapeutic options are evaluated individually by the treating physicians.
• Identification of the underlying pathogenic germline variant enables predictive testing of at-risk family members.

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