Benign hereditary chorea

Unlike other neurogenetic causes of chorea such as Huntington's disease, BHC is not progressive, and not associated with cognitive decline or psychiatric problems in the vast majority of cases.

Features reported in these families, including dystonia, tremor, and myoclonus, led researchers to question whether BHC actually represents different diagnoses with similar phenotypes inappropriately grouped together.

[2] BHC is caused by a single-nucleotide substitution mutation in TITF1, which encodes thyroid transcription factor 1 (TTF-1) and is inherited in an autosomal dominant pattern.

This gene is also known as NK2 homeobox 1 (NKX2-1)[2] The single-nucleotide substitution mutation then ultimately has drastic effects on the maturation processes of TITF-1[4] In some cases, additional developmental abnormalities of lung and thyroid tissue are found in BHC, leading to the suggested alternative name brain-lung-thyroid syndrome.

A wide spectrum of mutations have been reported, drawing a potential association between amount of subsequently deleted nucleotides to severity of symptoms.

This is because during embryonic development, NKX2.1 plays a key role in binding to transcriptional regulatory elements and proteins within those respective organs.

However, in 2002, the experimentally observed mutation of the gene leading to the BHC phenotype was identified, solidifying benign hereditary chorea as a disorder.

Looking closer at the region of the chromosome suspected of causing the disorder, researchers discovered that there was a 1.2 Mb deletion in the DNA that resulted in the loss of the TITF-1 gene.

[7] In 1978, BHC was reported to have a frequency of 1:500,000 within a Welsh population, but due to how some symptoms are hard to distinguish, it was concluded that the number is underrespresentative of actual clinical cases.