title: Benign hereditary chorea: phenotype, prognosis, therapeutic outcome and long term follow-up in a large series with new mutations in the TITF1/NKX2-1 gene.
abstract: BACKGROUND
  Benign hereditary chorea (BHC) is a rare autosomal dominant disorder characterised by childhood onset that tends to improve in adulthood. The associated gene, NKX2-1 (previously called TITF1), is essential for organogenesis of the basal ganglia, thyroid and lungs. The aim of the study was to refine the movement disorders phenotype. We also studied disease course and response to therapy in a large series of genetically proven patients.
  
  
  METHODS
  We analysed clinical, genetic findings and follow-up data in 28 NKX2-1 mutated BHC patients from 13 families.
  
  
  RESULTS
  All patients had private mutations, including seven new mutations, three previously reported mutations and three sporadic deletions encompassing the NKX2-1 gene. Hypotonia and chorea were present in early infancy, with delayed walking ability (25/28); dystonia, myoclonus and tics were often associated. Attention deficit hyperactivity disorder (ADHD) was present in seven. Among the 14 patients followed-up until adulthood, nine had persistent mild chorea, two had near total resolution of chorea but persistent disabling prominent myoclonus and three recovered completely. Learning difficulties were observed in 20/28 patients, and three had mental retardation. Various combinations of BHC, thyroid (67%) and lung (46%) features were noted. We found no genotype-phenotype correlation. A rapid and sustained beneficial effect on chorea was obtained in 5/8 patients treated with tetrabenazine.
  
  
  CONCLUSIONS
  Early onset chorea preceded by hypotonia is suggestive of BHC. Associated thyroid or respiratory disorders further support the diagnosis and call for genetic studies. Tetrabenazine may be an interesting option to treat disabling chorea.
authors: AP-HP, Service de Neuropédiatrie, Hôpital Trousseau, Paris, France.
authors: Domitille
authors: D
authors: Gras
authors: Laurence
authors: L
authors: Jonard
authors: Emmanuel
authors: E
authors: Roze
authors: Sandra
authors: S
authors: Chantot-Bastaraud
authors: Jeanette
authors: J
authors: Koht
authors: Jacques
authors: J
authors: Motte
authors: Diana
authors: D
authors: Rodriguez
authors: Malek
authors: M
authors: Louha
authors: Isabelle
authors: I
authors: Caubel
authors: Isabelle
authors: I
authors: Kemlin
authors: Laurence
authors: L
authors: Lion-François
authors: Cyril
authors: C
authors: Goizet
authors: Loic
authors: L
authors: Guillot
authors: Marie-Laure
authors: ML
authors: Moutard
authors: Ralph
authors: R
authors: Epaud
authors: Bénédicte
authors: B
authors: Héron
authors: Perrine
authors: P
authors: Charles
authors: Marilyn
authors: M
authors: Tallot
authors: Agnès
authors: A
authors: Camuzat
authors: Alexandra
authors: A
authors: Durr
authors: Michel
authors: M
authors: Polak
authors: David
authors: D
authors: Devos
authors: Damien
authors: D
authors: Sanlaville
authors: Isabelle
authors: I
authors: Vuillaume
authors: Thierry
authors: T
authors: Billette de Villemeur
authors: Marie
authors: M
authors: Vidailhet
authors: Diane
authors: D
authors: Doummar
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D017668:Age of Onset; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002819:Chorea / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D025063:Chromosome Disorders / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D003072:Cognition Disorders / Q000235:genetics; D003409:Congenital Hypothyroidism / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D005602:France; D005799:Genes, Dominant; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D009483:Neuropsychological Tests; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D011379:Prognosis; D040081:Protein Array Analysis; D012140:Respiratory Tract Diseases / Q000235:genetics; D013747:Tetrabenazine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D018759:Adrenergic Uptake Inhibitors; C000614412:NKX2-1 protein, human; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D013747:Tetrabenazine