Benign Hereditary Chorea: An Update

Benign hereditary chorea (BHC) is a childhood-onset, hyperkinetic movement disorder normally with little progression of motor symptoms into adult life. The disorder is caused by mutations to the NKX2.1 (TITF1) gene and also forms part of the “brain–lung–thyroid syndrome”, in which additional developmental abnormalities of lung and thyroid tissue are observed. In this review, we summarize the main clinical findings in “classical” BHC syndrome and discuss more recently reported atypical features, including non-choreiform movement phenotypes. We highlight additional non-motor characteristics such as cognitive impairment and psychiatric symptoms, while discussing the evidence for BHC as a developmental disorder involving impaired neural migration and other multisystem developmental abnormalities. Finally, we will discuss the efficacy of available therapies in both affected pediatric and adult cohorts. Delineation of the BHC disease spectrum will no doubt expand our understanding of this disorder, facilitating better targeting of genetic testing and establish a framework for future clinical trials.

• Publication year

  2015

• Venue

  Tremor and Other Hyperkinetic Movements

• Publication date

  2015-07-14

• Fields of study

  Medicine

• Identifiers
  DOI 10.7916/D8RJ4HM5PMID 26196025PMCID 4502401
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Redefining the Pediatric Phenotype of X-Linked Monocarboxylate Transporter 8 (MCT8) Deficiency

  2015cited by this paper
• Recurrent drop attacks in early childhood as presenting symptom of benign hereditary chorea caused by TITF1 gene mutations

  2015cited by this paper
• A de novo ADCY5 mutation causes early‐onset autosomal dominant chorea and dystonia

  2015cited by this paper
• SGCE and myoclonus dystonia: motor characteristics, diagnostic criteria and clinical predictors of genotype

  2014cited by this paper
• A Novel De Novo Mutation of the TITF1/NKX2-1 Gene Causing Ataxia, Benign Hereditary Chorea, Hypothyroidism and a Pituitary Mass in a UK Family and Review of the Literature

  2014cited by this paper
• Benign hereditary chorea related to NKX2.1: expansion of the genotypic and phenotypic spectrum

  2014cited by this paper
• NKX2-1 mutation in a family diagnosed with ataxic dyskinetic cerebral palsy.

  2013cited by this paper
• Benign hereditary chorea: clinical features and long-term follow-up in a Spanish family.

  2013cited by this paper
• Heterogeneous pulmonary phenotypes associated with mutations in the thyroid transcription factor gene NKX2-1.

  2013cited by this paper
• 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

  2012cited by this paper
• Hypoperfusion in caudate nuclei in patients with brain-lung-thyroid syndrome.

  2012cited by this paper
• Microdeletions detected using chromosome microarray in children with suspected genetic movement disorders: a single‐centre study

  2012cited by this paper
• Benign hereditary chorea 2: Pathological findings in an autopsy case

  2012cited by this paper
• TITF-1 gene mutation in a case of sporadic non-progressive chorea. Response to levodopa treatment.

  2012cited by this paper
• Multiplex Ligation-Dependent Probe Amplification Improves the Detection Rate of NKX2.1 Mutations in Patients Affected by Brain-Lung-Thyroid Syndrome

  2012cited by this paper
• A novel nonsense mutation in the TITF-1 gene in a Japanese family with benign hereditary chorea.

  2012cited by this paper
• Benign hereditary chorea: dopaminergic brain imaging in patients with a novel intronic NKX2.1 gene mutation

  2012cited by this paper
• Benign hereditary chorea: an update.

  2011cited by this paper
• Benign hereditary chorea: Clinical and neuroimaging features in an Italian family

  2010influential reference
• Pulmonary pathology in thyroid transcription factor-1 deficiency syndrome.

  2010cited by this paper
• Fatal neonatal respiratory failure in an infant with congenital hypothyroidism due to haploinsufficiency of the NKX2-1 gene: alteration of pulmonary surfactant homeostasis

  2010cited by this paper
• Advanced magnetic resonance imaging in benign hereditary chorea: Study of two familial cases

  2010cited by this paper
• Duplication of the pituitary stalk in a patient with a heterozygous deletion of chromosome 14 harboring the thyroid transcription factor-1 gene.

  2010cited by this paper
• Five new TTF1/NKX2.1 mutations in brain-lung-thyroid syndrome: rescue by PAX8 synergism in one case.

  2009cited by this paper
• Reversal of head drop after discontinuation of olanzapine in a DLB patient

  2008influential reference
• A Novel NKX2.1 Mutation in a Family with Hypothyroidism and Benign Hereditary Chorea

  2008cited by this paper
• The requirement of Nkx2-1 in the temporal specification of cortical interneuron subtypes.

  2008influential reference
• Characterizing the cancer genome in lung adenocarcinoma

  2007cited by this paper
• Novel locus for benign hereditary chorea with adult onset maps to chromosome 8q21.3 q23.3.

  2007cited by this paper
• Benign Hereditary Chorea: Clinical, Neuroimaging, and Genetic Findings

  2007cited by this paper
• Benign hereditary chorea revisited: A journey to understanding

  2007cited by this paper
• New syndromic form of benign hereditary chorea is associated with a deletion of TITF‐1 and PAX‐9 contiguous genes

  2006cited by this paper
• Functional study of a novel single deletion in the TITF1/NKX2.1 homeobox gene that produces congenital hypothyroidism and benign chorea but not pulmonary distress.

  2006cited by this paper
• Brain-Thyroid-Lung syndrome: a patient with a severe multi-system disorder due to a de novo mutation in the thyroid transcription factor 1 gene

  2005cited by this paper
• A novel TITF-1 mutation causes benign hereditary chorea with response to levodopa

  2005influential reference
• Alterations of striatal neurons in benign hereditary chorea

  2005cited by this paper
• Nonsense mutation in TITF1 in a Portuguese family with benign hereditary chorea

  2005cited by this paper
• Nkx2.1 transcription factor in lung cells and a transforming growth factor‐β1 heterozygous mouse model of lung carcinogenesis

  2004cited by this paper
• Autosomal dominant transmission of congenital hypothyroidism, neonatal respiratory distress, and ataxia caused by a mutation of NKX2-1.

  2004cited by this paper
• Benign hereditary chorea: Clinical, genetic, and pathological findings

  2003cited by this paper
• Nuclear Factor I/Thyroid Transcription Factor 1 Interactions Modulate Surfactant Protein C Transcription

  2003cited by this paper
• Choreoathetosis, hypothyroidism, and pulmonary alterations due to human NKX2-1 haploinsufficiency.

  2002cited by this paper
• Clinical and genetic heterogeneity in benign hereditary chorea

  2002cited by this paper
• Mutations in TITF-1 are associated with benign hereditary chorea.

  2002cited by this paper
• Hereditary benign chorea

  2001cited by this paper
• Benign hereditary chorea of early onset maps to chromosome 14q.

  2000cited by this paper
• Deletion of NKX2.1 gene encoding thyroid transcription factor-1 in two siblings with hypothyroidism and respiratory failure.

  2000cited by this paper
• 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.

  1999cited by this paper
• Benign hereditary chorea: Entity or syndrome?

  1999cited by this paper
• [Benign hereditary chorea].

  1999cited by this paper
• Deletion of thyroid transcription factor-1 gene in an infant with neonatal thyroid dysfunction and respiratory failure.

  1998cited by this paper
• A Dutch family with benign hereditary chorea of early onset: differentiation from Huntington's disease.

  1996cited by this paper
• The T/ebp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary.

  1996cited by this paper
• Longitudinal organization of the anterior neural plate and neural tube.

  1995cited by this paper
• Gene Structure and Expression of Human Thyroid Transcription Factor-1 in Respiratory Epithelial Cells (*)

  1995cited by this paper
• Lung Cell-specific Expression of the Murine Surfactant Protein A (SP-A) Gene Is Mediated by Interactions between the SP-A Promoter and Thyroid Transcription Factor-1 (*)

  1995cited by this paper
• Paediatric perspectives …

  1994cited by this paper
• Benign hereditary chorea.

  1993cited by this paper
• The transcription factor TTF-1 is expressed at the onset of thyroid and lung morphogenesis and in restricted regions of the foetal brain.

  1991cited by this paper
• Hereditary progressive chorea without dementia.

  1988cited by this paper
• Cerebral metabolism of glucose in benign hereditary chorea

  1986cited by this paper
• Chorée familiale, non progressive, liée au sexe.

  1984cited by this paper
• Benign familial chorea: an association with intellectual impairment.

  1984cited by this paper
• [Sex-linked, nonprogressive, familial chorea].

  1984cited by this paper
• Benign (non-paroxysmal) familial chorea. Paediatric perspectives.

  1981cited by this paper
• Benign hereditary chorea Clinical and genetic aspects

  1978cited by this paper
• Familial nonprogressive involuntary movements of childhood

  1977cited by this paper
• Familial essential ("benign") chorea.

  1976cited by this paper
• Benign hereditary non-progressive chorea of early onset. Clinical genetics of the syndrome and report of a new family.

  1976cited by this paper
• Benign, recessively inherited choreo-athetosis of early onset.

  1969cited by this paper
• Hereditary nonprogressive chorea of early onset.

  1967cited by this paper

• A novel mutation of the NKX2-1 gene: A late-onset diagnosis of benign hereditary chorea

  2025cites this paper
• Update on Genetic Chorea

  2025cites this paper
• Exploring the Genetic Landscape of Chorea in Infancy and Early Childhood: Implications for Diagnosis and Treatment

  2024cites this paper
• Insights from European Reference Network for rare neurological disorders study surveys on diagnosis, treatment, and management of NKX2-1-related disorders.

  2024cites this paper
• Bilateral deep brain stimulation (DBS) of globus pallidus internus (GPi) for the treatment of benign hereditary chorea and other childhood onset choreas: a single-center experience

  2024cites this paper
• The First Indian Patient With Benign Hereditary Chorea due to a De Novo Mutation in the NKX2-1 Gene

  2024cites this paper
• Chorea: An unusual manifestation of endocrine diseases

  2023cites this paper
• Otros trastornos del movimiento, tics, corea

  2023cites this paper
• A comprehensive update on genetic inheritance, epigenetic factors, associated pathology, and recent therapeutic intervention by gene therapy in schizophrenia

  2023cites this paper
• Combining Literature Review With a Ground Truth Approach for Diagnosing Huntington's Disease Phenocopy

  2022cites this paper
• Diagnostic Dilemma and Management Difficulties in a Young Patient With Psychosis and Benign Chorea: A Case Report and Review of the Literature

  2022cites this paper
• Detection and Characterization of a De Novo Alu Retrotransposition Event Causing NKX2‐1‐Related Disorder

  2022cites this paper
• A case of brain-lung-thyroid syndrome.

  2022cites this paper
• Chorea

  2022cites this paper
• NK2 homeobox gene cluster: Functions and roles in human diseases

  2022cites this paper
• Working memory, attention and planning abilities in NKX2.1-related chorea.

  2021cites this paper
• Deletion of conserved non‐coding sequences downstream from NKX2‐1: A novel disease‐causing mechanism for benign hereditary chorea

  2021cites this paper
• Movement Disorders in Children

  2021cites this paper
• Challenges in Clinicogenetic Correlations: One Gene – Many Phenotypes

  2021cites this paper
• Growth hormone deficiency in a child with benign hereditary chorea caused by a de novo mutation of the TITF1/NKX2-1 gene

  2021cites this paper
• Huntington’s disease: diagnosis and management

  2021cites this paper
• Treatable Movement Disorders of Infancy and Early Childhood

  2020cites this paper
• Phenomenology of Chorea

  2020cites this paper
• Review of Hereditary and Acquired Rare Choreas

  2020cites this paper
• Benign hereditary chorea: From benign to serious.

  2020cites this paper
• Chorea.

  2019cites this paper
• Chiari Malformation Type I in a Patient with a Novel NKX2-1 Mutation

  2019cites this paper
• A Not So Benign Family Pedigree With Hereditary Chorea: A Broader Phenotypic Expression or Additional Picture?

  2019cites this paper
• The Clinical Neuropsychiatry of “Organic” Obsessive-Compulsive Disorder

  2019cites this paper
• Restless Legs Syndrome in NKX2-1-related chorea: An expansion of the disease spectrum.

  2019cites this paper
• Multiple Causes of Pediatric Early Onset Chorea—Clinical and Genetic Approach

  2018cites this paper
• Is Benign Hereditary Chorea Really Benign? Brain‐Lung‐Thyroid Syndrome Caused by NKX2‐1 Mutations

  2018cites this paper
• Genetic basis for childhood interstitial lung disease among Japanese infants and children

  2018cites this paper
• Benign hereditary chorea and deletions outside NKX2-1: What's the role of MBIP?

  2018cites this paper
• [Movement disorders: An update].

  2018cites this paper
• NKX2-1 New Mutation Associated With Myoclonus, Dystonia, and Pituitary Involvement

  2018cites this paper
• The Movement Disorder of Brain-Lung-Thyroid Syndrome Can be Responsive to Methylphenidate

  2017cites this paper
• NKX2-1 Is Required in the Embryonic Septum for Cholinergic System Development, Learning, and Memory

  2017cites this paper
• A Case of Previously Unsuspected Huntington Disease Diagnosed at Autopsy

  2017cites this paper
• Altérations de l'expression de la protéine A du surfactant dans les pneumopathies interstitielles diffuses

  2016cites this paper
• Benign hereditary chorea, not only chorea: a family case presentation

  2016cites this paper
• A Role for the Transcription Factor Nk2 Homeobox 1 in Schizophrenia: Convergent Evidence from Animal and Human Studies

  2016cites this paper
• Treatment of ADCY5-Associated Dystonia, Chorea, and Hyperkinetic Disorders With Deep Brain Stimulation

  2016cites this paper
• Recent advances in genetics of chorea.

  2016cites this paper
• De Novo Mutations in PDE10A Cause Childhood-Onset Chorea with Bilateral Striatal Lesions

  2016cites this paper
• A Video Report of Brain–Lung–Thyroid Syndrome in a Japanese Female With a Novel Frameshift Mutation of the NKX2-1 Gene

  2016cites this paper
• Respiratory Distress, Congenital Hypothyroidism and Hypotonia in a Newborn

  2016cites this paper
• Movement Disorders Presenting in Childhood

  2016cites this paper
• Transcription Factors in Schizophrenia: A Current View of Genetic Aspects

  2016cites this paper
• Huntington's Disease, Huntington's Disease Look‐Alikes‎, and Benign Hereditary Chorea: What's New?

  2016cites this paper
• Functional characterization of two novel mutations in TTF-1/NKX2.1 homeodomain in patients with benign hereditary chorea.

  2016cites this paper
• ADCY5 mutations are another cause of benign hereditary chorea

  2016cites this paper
• ADCY5 Mutations and Benign Hereditary Chorea.

  2015cites this paper
• Синдром мозг – легкие – щитовидная железа

  2015cites this paper
• ADCY5 Mutations and Benign Hereditary Chorea

  2015cites this paper
• NKX2.1-Related Disorders: a novel mutation with mild clinical presentation

  2015cites this paper
• ADCY5 mutations are another cause of benign hereditary chorea

  2015cites this paper
• Recurrent drop attacks in early childhood as presenting symptom of benign hereditary chorea caused by TITF1 gene mutations

  2015cites this paper
• Comprehensive genotyping and clinical characterisation reveal 27 novel NKX2-1 mutations and expand the phenotypic spectrum

  2014cites this paper
• Benign hereditary chorea related to NKX2.1: expansion of the genotypic and phenotypic spectrum

  2014cites this paper
• Genetic disorders of thyroid metabolism and brain development

  2014cites this paper
• A Novel De Novo Mutation of the TITF1/NKX2-1 Gene Causing Ataxia, Benign Hereditary Chorea, Hypothyroidism and a Pituitary Mass in a UK Family and Review of the Literature

  2014cites this paper
• NKX2-1 mutation in a family diagnosed with ataxic dyskinetic cerebral palsy.

  2013cites this paper
• Action selection in a possible model of striatal medium spiny neuron dysfunction: behavioral and EEG data in a patient with benign hereditary chorea

  2013influential citation
• Neuroimage: Clinical Striatal Disorders Dissociate Mechanisms of Enhanced and Impaired Response Selection — Evidence from Cognitive Neurophysiology and Computational Modelling

  year unknowncites this paper