NKX2-1 New Mutation Associated With Myoclonus, Dystonia, and Pituitary Involvement

Background: NKX2-1 related disorders (also known as brain-lung-thyroid syndrome or benign hereditary chorea 1) are associated with a wide spectrum of symptoms. The core features are various movement disorders, characteristically chorea, less frequently myoclonus, dystonia, ataxia; thyroid disease; a...

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Autores principales: Balicza, Péter, Grosz, Zoltán, Molnár, Viktor, Illés, Anett, Csabán, Dora, Gézsi, Andras, Dézsi, Lívia, Zádori, Dénes, Vécsei, László, Molnár, Mária Judit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113386/
https://www.ncbi.nlm.nih.gov/pubmed/30186310
http://dx.doi.org/10.3389/fgene.2018.00335
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author Balicza, Péter
Grosz, Zoltán
Molnár, Viktor
Illés, Anett
Csabán, Dora
Gézsi, Andras
Dézsi, Lívia
Zádori, Dénes
Vécsei, László
Molnár, Mária Judit
author_facet Balicza, Péter
Grosz, Zoltán
Molnár, Viktor
Illés, Anett
Csabán, Dora
Gézsi, Andras
Dézsi, Lívia
Zádori, Dénes
Vécsei, László
Molnár, Mária Judit
author_sort Balicza, Péter
collection PubMed
description Background: NKX2-1 related disorders (also known as brain-lung-thyroid syndrome or benign hereditary chorea 1) are associated with a wide spectrum of symptoms. The core features are various movement disorders, characteristically chorea, less frequently myoclonus, dystonia, ataxia; thyroid disease; and lung involvement. The full triad is present in 50% of affected individuals. Numerous additional symptoms may be associated, although many of these were reported only in single cases. Pituitary dysfunction was ambiguously linked to NKX2-1 haploinsufficiency previously. Case Presentation: We examined two members of a family with motor developmental delay, mixed movement disorder (myoclonus, dystonia and chorea) and endocrinological abnormalities (peripheric thyroid disease, and pituitary hormone deficiencies). Dystonia predominated at the father, and myoclonus at the daughter. The father had hypogonadotropic hypogonadism, while the daughter was treated with growth hormone deficiency. Both patients had empty sella on MRI. Candidate gene analyses were negative. Exome sequencing detected a pathogenic stop variation (NM_003317:c.338G>A, p.Trp113(*)) in the NKX2-1 gene. Conclusions: This case study has two highlights. (1) It draws attention to possible pituitary dysfunction in brain-lung-thyroid syndrome, and provide further evidences that this might be linked to loss of function of the NKX2-1 gene. (2) It underscores the importance of considering NKX2-1 related disorders in the differential diagnosis of myoclonus dystonia.
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spelling pubmed-61133862018-09-05 NKX2-1 New Mutation Associated With Myoclonus, Dystonia, and Pituitary Involvement Balicza, Péter Grosz, Zoltán Molnár, Viktor Illés, Anett Csabán, Dora Gézsi, Andras Dézsi, Lívia Zádori, Dénes Vécsei, László Molnár, Mária Judit Front Genet Genetics Background: NKX2-1 related disorders (also known as brain-lung-thyroid syndrome or benign hereditary chorea 1) are associated with a wide spectrum of symptoms. The core features are various movement disorders, characteristically chorea, less frequently myoclonus, dystonia, ataxia; thyroid disease; and lung involvement. The full triad is present in 50% of affected individuals. Numerous additional symptoms may be associated, although many of these were reported only in single cases. Pituitary dysfunction was ambiguously linked to NKX2-1 haploinsufficiency previously. Case Presentation: We examined two members of a family with motor developmental delay, mixed movement disorder (myoclonus, dystonia and chorea) and endocrinological abnormalities (peripheric thyroid disease, and pituitary hormone deficiencies). Dystonia predominated at the father, and myoclonus at the daughter. The father had hypogonadotropic hypogonadism, while the daughter was treated with growth hormone deficiency. Both patients had empty sella on MRI. Candidate gene analyses were negative. Exome sequencing detected a pathogenic stop variation (NM_003317:c.338G>A, p.Trp113(*)) in the NKX2-1 gene. Conclusions: This case study has two highlights. (1) It draws attention to possible pituitary dysfunction in brain-lung-thyroid syndrome, and provide further evidences that this might be linked to loss of function of the NKX2-1 gene. (2) It underscores the importance of considering NKX2-1 related disorders in the differential diagnosis of myoclonus dystonia. Frontiers Media S.A. 2018-08-22 /pmc/articles/PMC6113386/ /pubmed/30186310 http://dx.doi.org/10.3389/fgene.2018.00335 Text en Copyright © 2018 Balicza, Grosz, Molnár, Illés, Csabán, Gézsi, Dézsi, Zádori, Vécsei and Molnár. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Balicza, Péter
Grosz, Zoltán
Molnár, Viktor
Illés, Anett
Csabán, Dora
Gézsi, Andras
Dézsi, Lívia
Zádori, Dénes
Vécsei, László
Molnár, Mária Judit
NKX2-1 New Mutation Associated With Myoclonus, Dystonia, and Pituitary Involvement
title NKX2-1 New Mutation Associated With Myoclonus, Dystonia, and Pituitary Involvement
title_full NKX2-1 New Mutation Associated With Myoclonus, Dystonia, and Pituitary Involvement
title_fullStr NKX2-1 New Mutation Associated With Myoclonus, Dystonia, and Pituitary Involvement
title_full_unstemmed NKX2-1 New Mutation Associated With Myoclonus, Dystonia, and Pituitary Involvement
title_short NKX2-1 New Mutation Associated With Myoclonus, Dystonia, and Pituitary Involvement
title_sort nkx2-1 new mutation associated with myoclonus, dystonia, and pituitary involvement
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113386/
https://www.ncbi.nlm.nih.gov/pubmed/30186310
http://dx.doi.org/10.3389/fgene.2018.00335
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