Benign hereditary chorea (BHC) is a rare, autosomal dominant movement disorder characterized by non-progressive choreiform movements beginning in childhood. Unlike other hereditary choreas such as Huntington disease, BHC is distinguished by its benign course—patients maintain normal cognition and have a normal life expectancy[1]. The condition was first described by Bruyn and colleagues in 1968 and has since been linked to mutations in several genes, most commonly NKX2-1 (also known as TTF-1)[2].
BHC represents a genetically heterogeneous group of disorders, with mutations in at least three genes (NKX2-1, ADCY5, and TRIO) identified as causative. The clinical phenotype extends beyond pure chorea in many cases, with some patients exhibiting additional neurological features including hypotonia, developmental delay, and respiratory difficulties[3].
Benign hereditary chorea is rare, with estimated prevalence of less than 1 in 500,000 individuals[1:1]. The condition follows an autosomal dominant inheritance pattern with high penetrance, though expressivity is variable. Both males and females are equally affected. Onset typically occurs in early childhood, often before age 5 years, though mild chorea may not be recognized until later[2:1].
The disorder has been reported in families of various ethnic backgrounds, though population-specific prevalence data are limited. Due to its rarity and the subtlety of symptoms in some individuals, BHC is likely underdiagnosed[3:1].
NKX2-1 mutations[1:2]:
ADCY5 mutations[2:2]:
TRIO mutations[3:2]:
All identified causes follow autosomal dominant inheritance[1:3]. However, some cases appear de novo without family history. The variability in expression even within families suggests the influence of modifier genes or environmental factors.
The pathophysiology of BHC involves dysfunction of basal ganglia circuits, particularly involving the striatum[2:3]:
Current evidence suggests BHC results from dysfunction in dopaminergic signaling within the basal ganglia[3:3]:
Chorea[1:4]:
Motor Development[2:4]:
In NKX2-1 related BHC[2:5]:
In ADCY5 related BHC[3:4]:
Behavioral and Cognitive[1:5]:
The natural history of BHC is characterized by[1:6][3:5]:
BHC is a clinical diagnosis based on[1:7]:
Genetic testing is recommended to confirm the diagnosis and identify the specific cause[2:6]:
| Condition | Key Distinguishing Features |
|---|---|
| Huntington disease | Progressive, adult onset, cognitive decline |
| Wilson disease | Kayser-Fleischer rings, hepatic disease |
| Chorea-acanthocytosis | Acanthocytes, elevated CK |
| Sydenham chorea | Associated with rheumatic fever, younger age |
| Transient chorea of infancy | Self-limited, resolves by age 2-3 |
Treatment for BHC is often unnecessary given the benign natural history[1:8]. When treatment is required:
For mild chorea[2:7]:
For moderate to severe chorea[3:6]:
For ADCY5-related BHC[2:8]:
For NKX2-1-related BHC[2:9]:
The prognosis for BHC is generally favorable[1:9][3:7]:
Most individuals with BHC:
BHC exists on a spectrum with other hereditary choreas and represents the benign end of a phenotypic continuum[2:10]. It is important to distinguish from:
Recent research on Benign Hereditary Chorea includes:
Kleiner-Fisman G, Lang AE. Benign hereditary chorea. Handb Clin Neurol. 2021. ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎
Patel NJ, Jankovic J. NKX2-1-related chorea. Mov Disord. 2020. ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎
Mencacci NE, et al. ADCY5 mutations in benign hereditary chorea. J Med Genet. 2019. ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎