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
J Neurol Neurosurg Psychiatry. 2012-07-24; 83(10): 956-962
DOI: 10.1136/JNNP-2012-302505
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1. J Neurol Neurosurg Psychiatry. 2012 Oct;83(10):956-62. doi:
10.1136/jnnp-2012-302505. Epub 2012 Jul 24.
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.
Gras D(1), Jonard L, Roze E, Chantot-Bastaraud S, Koht J, Motte J, Rodriguez D,
Louha M, Caubel I, Kemlin I, Lion-François L, Goizet C, Guillot L, Moutard ML,
Epaud R, Héron B, Charles P, Tallot M, Camuzat A, Durr A, Polak M, Devos D,
Sanlaville D, Vuillaume I, Billette de Villemeur T, Vidailhet M, Doummar D.
Author information:
(1)AP-HP, Service de Neuropédiatrie, Hôpital Trousseau, Paris, France.
Comment in
J Neurol Neurosurg Psychiatry. 2012 Oct;83(10):950-1.
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.
CONCLUSION: 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.
DOI: 10.1136/jnnp-2012-302505
PMID: 22832740 [Indexed for MEDLINE]