Benign hereditary chorea
Rare non-progressive chorea linked to TITF1 mutation.
Benign hereditary chorea (BHC), also known as benign familial chorea, is a rare autosomal dominant neurogenetic syndrome. It typically presents in childhood with isolated chorea and average to below average intelligence, and is not progressive or associated with cognitive decline or psychiatric problems in most cases. The disorder was first described in 1967 in an African American family from Mississippi.
- first_described
- 1967
- inheritance
- Autosomal dominant
- causative_gene
- TITF1 (NKX2-1) on chromosome 14
- typical_onset
- Childhood
- frequency
- 1:500,000 in a Welsh population (1978)
- alternative_name
- Brain-lung-thyroid syndrome
Lore & Background
The first description of BHC was reported in 1967 in an African American family from Mississippi, where two brothers had delayed motor development and were diagnosed with chorea. Subsequent families showed similar traits, suggesting an autosomal dominant pattern, but heterogeneity in presentations—including dystonia, tremor, and myoclonus—led researchers to question whether BHC represented different diagnoses grouped together. In 2000, a connection between a Dutch family and one of the original families identified a disease locus on the long arm of chromosome 14. In 2002, an Italian family with the same linkage was studied, revealing a 1.2 Mb deletion that resulted in loss of the TITF-1 gene, confirming the genetic cause.
Reader's Guide
Benign hereditary chorea is significant as one of the few non-progressive choreic disorders, distinguishing it from conditions like Huntington's disease. Its recognition as a distinct entity was controversial for decades due to phenotypic overlap with other movement disorders. The identification of TITF-1 mutations in 2002 solidified BHC as a discrete syndrome and enabled genetic confirmation. The disorder highlights the role of thyroid transcription factor 1 in brain, lung, and thyroid development, reflected in the alternative name brain-lung-thyroid syndrome. Management remains symptomatic, with levodopa and methylphenidate reported to improve chorea, though no cure exists. The reported frequency of 1:500,000 in a Welsh population is likely an underestimate due to diagnostic difficulty.
Did You Know?
- BHC was first described in 1967 in an African American family from Mississippi.
- The disorder is caused by mutations in TITF1 (NKX2-1), which can include deletions, frameshifts, and single-nucleotide substitutions.
- In 2002, a 1.2 Mb deletion resulting in loss of the TITF-1 gene was identified in an Italian family.
- Levodopa's effect on chorea-related gait in BHC is variable and not a consistently proven outcome in the literature.
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