Brain-Lung-Thyroid Disease

Abstract

Brain-lung-thyroid disease is a rare familial disorder caused by mutations in thyroid transcription factor 1, a gene that regulates neuronal migration. We report the clinical features of ten patients from a single family with a novel gene mutation, including observations regarding treatment. Neurologic features of the kindred included developmental delay, learning difficulties, psychosis, chorea, and dystonia. Three patients had a history of seizure, which has not been previously reported in genetically confirmed cases. Low-dose dopamine-receptor blocking drugs were poorly tolerated in 2 patients who received this therapy, levodopa improved chorea in 3 of 4 children, and diazepam was markedly effective in a single adult patient. Chorea related to brain-lung-thyroid disease appears to respond paradoxically to antidopaminergic drugs. The unusual therapeutic response seen in our patients and others may help elucidate how disease-related migratory deficits affect neural pathways associated with motor control.

Keywords

chorea brain-lung-thyroid disease

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References

Kawano

Horie

Honma

Kawamura

Takeuchi

Kimura

Aberrant trajectory of ascending dopaminergic pathway in mice lacking Nkx2.1. Exp Neurol. 2003;182:103–112.

Sussel

Marin

Kimura

Rubenstein

JL.

Loss of Nkx2.1 homeobox gene function results in a ventral to dorsal molecular respecification within the basal telencephalon: evidence for a transformation of the pallidum into the striatum. Development. 1999;126:3359–3370.

Moeller

Kimura

Kusakabe

Liao

Van Sande

Refetoff

Hypothyroidism in thyroid transcription factor 1 haploinsufficiency is caused by reduced expression of the thyroid-stimulating hormone receptor. Mol Endocrinol. 2003;17:2295–2302.

Kolla

Gonzales

. Thyroid transcription factor in differentiating type II cells: regulation, isoforms, and target genes. Am J Respir Cell Mol Biol. 2007;36:213–225.

Carré

Szinnai

Castanet

. Five new TTF1/NKX2.1 mutations in brain-lung-thyroid syndrome: rescue by PAX8 synergism in one case. Hum Mol Genet. 2009;18:2266–2276.

Iwatani

Mabe

Devriendt

Kodama

Miike

Deletion of NKX2.1 gene encoding thyroid transcription factor-1 in two siblings with hypothyroidism and respiratory failure. J Pediatr. 2000;137:272–276.

Devos

Vuillaume

de Becdelievre

. New syndromic form of benign hereditary chorea is associated with a deletion of TITF-1 and PAX-9 contiguous genes. Mov Disord. 2006;21:2237–2240.

Schrag

Quinn

Bhatia

Marsden

CD.

Benign hereditary chorea—entity or syndrome?

Mov Disord. 2000;15:280–288.

Breedveld

van Dongen

Danesino

. Mutations in TITF-1 are associated with benign hereditary chorea. Hum Mol Genet. 2002;11:971–979.

10.

Huntington Study Group. Unified Huntington’s Disease Rating Scale: reliability and consistency. Mov Disord. 1996;11:136–142.

11.

Doyle

Gonzalez

Thomas

Scavina

Autosomal dominant transmission of congenital hypothyroidism, neonatal respiratory distress, and ataxia caused by a mutation of NKX2.1. J Pediatr. 2004;145:190–193.

12.

Appollonio

Leone

Isella

. The Frontal Assessment Battery (FAB): normative values in an Italian population sample. Neurol Sci. 2005;26:108–116.

13.

Asmus

Horber

Pohlenz

. A novel TITF-1 mutation causes benign hereditary chorea with response to levodopa. Neurology. 2005;64:1952–1954.

14.

de Vries

Arts

Breedveld

Hoogeboom

Niermeijer

Heutink

Benign hereditary chorea of early onset maps to chromosome 14q. Am J Hum Genet. 2000;66:136–142.

15.

Ferrara

De Michele

Salvatore

. A novel NKX2.1 mutation in a family with hypothyroidism and benign hereditary chorea. Thyroid. 2008;18:1005–1009.

16.

Glik

Vuillaume

Devos

Inzelberg

Psychosis, short stature in benign hereditary chorea: a novel thyroid transcription factor-1 mutation. Mov Disord. 2008;23:1744–1747.

17.

Salvatore

Di Maio

Filla

. Benign hereditary chorea: clinical and neuroimaging features in an Italian family. Mov Disord. 2010;25:1491–1496.

18.

Bird

Carlson

Hall

JG.

Familial essential (“benign”) chorea. J Med Genet. 1976;13:357–362.

19.

Fernandez

Raskind

Matsushita

Wolff

Lipe

Bird

Hereditary benign chorea: clinical and genetic features of a distinct disease. Neurology. 2001;57:106–110.

20.

Landrieu

Benchet

Tardieu

Lapresle

Choree familiale, non progressive, liee au sexe. Rev Neurol. (Paris) 1984;140:432–433.

21.

Butt

Sousa

Fuccillo

. The requirement of Nkx2-1 in the temporal specification of cortical interneuron subtypes. Neuron. 2008;59:722–732.

22.

Friederich

RL.

Benign hereditary chorea improved on stimulant therapy. Pediatr Neurol. 1996;14:326–327.

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