title: Benign hereditary chorea related to NKX2.1: expansion of the genotypic and phenotypic spectrum.
abstract: OBJECTIVE
  Benign hereditary chorea is a dominantly inherited, childhood-onset hyperkinetic movement disorder characterized by non-progressive chorea and variable degrees of thyroid and respiratory involvement. Loss-of-function mutations in NKX2.1, a gene vital to the normal development and function of the brain, lungs, and thyroid, have been identified in a number of individuals.
  
  
  METHODS
  Clinical data from individuals with benign hereditary chorea identified through paediatric neurology services were collected in a standardized format. The NKX2.1 gene was analysed by Sanger sequencing, multiplex ligation-dependent probe amplification, and microarray analysis.
  
  
  RESULTS
  Six of our cohort were female and four male, median age at assessment was 8 years 6 months (range 1 y 6 mo-18 y). We identified 10 probands with NKX2.1 mutations; nine of these mutations are novel (including two whole-gene deletions) and one has been previously reported. Of the 10 individuals, eight presented with muscle hypotonia and four had evidence of hypothyroidism or respiratory involvement. Only three out of the 10 individuals had the full triad of 'brain-lung-thyroid syndrome' symptoms. Additional clinical characteristics occurring in individual participants included growth hormone deficiency, pes cavus, kyphosis, duplex kidney, and obsessive-compulsive disorder.
  
  
  CONCLUSIONS
  Our data suggest that the neurological phenotype is prominent in this condition and that many patients with benign hereditary chorea do not have the classic triad of brain-lung-thyroid syndrome. The extended phenotype may include obsessive-compulsive disorder and skeletal abnormalities.
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine & Clinical Neurosciences, Cardiff University, Cardiff, UK.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Peall
authors.forename: Daniel
authors.initials: D
authors.lastname: Lumsden
authors.forename: Rachel
authors.initials: R
authors.lastname: Kneen
authors.forename: Rajesh
authors.initials: R
authors.lastname: Madhu
authors.forename: Deirdre
authors.initials: D
authors.lastname: Peake
authors.forename: Frances
authors.initials: F
authors.lastname: Gibbon
authors.forename: Hilary
authors.initials: H
authors.lastname: Lewis
authors.forename: Tammy
authors.initials: T
authors.lastname: Hedderly
authors.forename: Esther
authors.initials: E
authors.lastname: Meyer
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Robb
authors.forename: Bryan
authors.initials: B
authors.lastname: Lynch
authors.forename: Mary D
authors.initials: MD
authors.lastname: King
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Lin
authors.forename: Huw R
authors.initials: HR
authors.lastname: Morris
authors.forename: Heinz
authors.initials: H
authors.lastname: Jungbluth
authors.forename: Manju A
authors.initials: MA
authors.lastname: Kurian
mesh_terms: D000293:Adolescent; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002819:Chorea / Q000150:complications* / Q000188:drug therapy / Q000235:genetics*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006801:Humans; D007037:Hypothyroidism / Q000150:complications / Q000235:genetics; D007223:Infant; D008297:Male; D009123:Muscle Hypotonia / Q000150:complications / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009460:Neurologic Examination; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D012120:Respiration Disorders / Q000150:complications / Q000235:genetics; D013961:Thyroid Gland / Q000473:pathology; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors