NKX2-1 new mutation associated with myoclonus, dystonia, and pituitary involvement

Péter Balicza, Zoltán Grosz, Viktor Molnár, Anett Illés, Dora Csabán, Andras Gézsi, Lívia Dézsi, Dénes Zádori, L. Vécsei, Mária Judit Molnár

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number335
JournalFrontiers in Genetics
Volume9
Issue numberAUG
DOIs
Publication statusPublished - Aug 22 2018

Fingerprint

Chorea
Thyroid Diseases
Movement Disorders
Nuclear Family
Fathers
Mutation
Exome
Haploinsufficiency
Myoclonus
Hypogonadism
Pituitary Hormones
Dystonia
Genetic Association Studies
Thyroid Hormones
Growth Hormone
Genes
Differential Diagnosis
Lung
Myoclonic dystonia
Choreoathetosis, Hypothyroidism, And Neonatal Respiratory Distress

Keywords

  • Benign hereditary chorea
  • Brain-lung-thyroid syndrome
  • Chorea
  • Empty sella
  • Myoclonus dystonia
  • NKX2-1 gene
  • NKX2-1 related disorders
  • Pituitary

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Genetics(clinical)

Cite this

Balicza, P., Grosz, Z., Molnár, V., Illés, A., Csabán, D., Gézsi, A., ... Molnár, M. J. (2018). NKX2-1 new mutation associated with myoclonus, dystonia, and pituitary involvement. Frontiers in Genetics, 9(AUG), [335]. https://doi.org/10.3389/fgene.2018.00335

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, L.; Molnár, Mária Judit.

In: Frontiers in Genetics, Vol. 9, No. AUG, 335, 22.08.2018.

Research output: Contribution to journalArticle

Balicza, P, Grosz, Z, Molnár, V, Illés, A, Csabán, D, Gézsi, A, Dézsi, L, Zádori, D, Vécsei, L & Molnár, MJ 2018, 'NKX2-1 new mutation associated with myoclonus, dystonia, and pituitary involvement', Frontiers in Genetics, vol. 9, no. AUG, 335. https://doi.org/10.3389/fgene.2018.00335
Balicza P, Grosz Z, Molnár V, Illés A, Csabán D, Gézsi A et al. NKX2-1 new mutation associated with myoclonus, dystonia, and pituitary involvement. Frontiers in Genetics. 2018 Aug 22;9(AUG). 335. https://doi.org/10.3389/fgene.2018.00335
Balicza, Péter ; Grosz, Zoltán ; Molnár, Viktor ; Illés, Anett ; Csabán, Dora ; Gézsi, Andras ; Dézsi, Lívia ; Zádori, Dénes ; Vécsei, L. ; Molnár, Mária Judit. / NKX2-1 new mutation associated with myoclonus, dystonia, and pituitary involvement. In: Frontiers in Genetics. 2018 ; Vol. 9, No. AUG.
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abstract = "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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AU - Csabán, Dora

AU - Gézsi, Andras

AU - Dézsi, Lívia

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