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Benign hereditary chorea(BHC)

MedGen UID:
98278
Concept ID:
C0393584
Disease or Syndrome
Synonyms: BHC; HEREDITARY PROGRESSIVE CHOREA WITHOUT DEMENTIA
SNOMED CT: Benign hereditary chorea (230306001)
 
Gene (location): NKX2-1 (14q13.3)
 
Monarch Initiative: MONDO:0021011
OMIM®: 118700

Disease characteristics

Excerpted from the GeneReview: NKX2-1-Related Disorders
NKX2-1-related disorders range from benign hereditary chorea (BHC) to choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress syndrome (also known as brain-lung-thyroid syndrome). Childhood-onset chorea, the hallmark feature of NKX2-1-related disorders, may or may not be associated with pulmonary disease or congenital hypothyroidism. Age of onset of chorea varies from early infancy (most commonly) to late childhood or adolescence and may progress into the second decade, after which it remains static or (rarely) remits. Pulmonary disease, the second most common manifestation, can include respiratory distress syndrome in neonates, interstitial lung disease in young children, and pulmonary fibrosis in older individuals. The risk for pulmonary carcinoma is increased in young adults with NKX2-1-related disorders. Thyroid dysfunction, occurring as a result of thyroid dysgenesis, can present as congenital or compensated hypothyroidism. In one review, 50% of affected individuals had the full brain-lung-thyroid syndrome, 30% had brain and thyroid involvement only, and 13% had chorea only. [from GeneReviews]
Authors:
Neepa Jayant Patel  |  Joseph Jankovic   view full author information

Additional descriptions

From OMIM
Benign hereditary chorea (BHC) is an autosomal dominant movement disorder that manifests before age 5 years and has a stationary or only slightly progressive course. Intelligence is normal or slightly below normal and mental deterioration is not seen. In some families, the choreic movements decrease during adolescence or early adulthood (summary by Breedveld et al., 2002).  http://www.omim.org/entry/118700
From MedlinePlus Genetics
Brain-lung-thyroid syndrome is a group of conditions that affect the brain, lungs, and thyroid gland (a butterfly-shaped gland in the lower neck). Brain-lung-thyroid syndrome historically included problems with all three organs, although the designation now encompasses a combination of brain, lung, and thyroid problems. About 50 percent of affected individuals have problems with all three organs, about 30 percent have brain and thyroid problems, and about 10 percent have brain and lung problems. The brain alone is affected in 10 to 20 percent of people with the condition. Such cases are sometimes called isolated benign hereditary chorea.

Nearly everyone with brain-lung-thyroid syndrome has brain-related movement abnormalities. Benign hereditary chorea is the most common feature of the syndrome. This feature is associated with involuntary jerking movements (chorea) of the face, torso, and limbs; writhing movements (athetosis) of the limbs; and other movement problems. Individuals with brain-lung-thyroid syndrome can have other abnormalities, such as difficulty coordinating movements (ataxia), muscle twitches (myoclonus), and involuntary muscle contractions that result in twisting and repetitive movements (dystonia). The movement problems typically begin around age 1, although they can begin in early infancy or later in life, and are often preceded by weak muscle tone (hypotonia). They can delay the development of walking. The movement problems usually remain stable and can improve over time. Some affected individuals also have learning difficulties or intellectual disability.

Lung problems are common in brain-lung-thyroid syndrome. Some affected newborns have respiratory distress syndrome, which causes extreme difficulty breathing and can be life-threatening. Other affected individuals develop widespread lung damage (interstitial lung disease) or scarring in the lungs (pulmonary fibrosis), both of which can also lead to breathing problems. Recurrent lung infections, which can be life-threatening, also occur in people with brain-lung-thyroid syndrome. People with brain-lung-thyroid syndrome have a higher risk of developing lung cancer than do people in the general population.

Thyroid problems are the next most common feature of brain-lung-thyroid syndrome. The thyroid gland makes hormones that help regulate a wide variety of critical body functions, including growth, brain development, and the rate of chemical reactions in the body (metabolism). Many affected individuals have reduced thyroid function from birth (congenital hypothyroidism), resulting in lower-than-normal levels of thyroid hormones. Others have a milder condition called compensated or subclinical hypothyroidism, in which thyroid hormone levels are within the normal range, even though the thyroid is not functioning properly. While most people with brain-lung-thyroid syndrome have a normal-sized thyroid, the gland is reduced in size (hypoplastic) or absent (aplastic) in some affected individuals. Although a shortage of thyroid hormones can cause intellectual disability and other neurological problems, it is unclear whether such issues in individuals with brain-lung-thyroid syndrome are due to hypothyroidism or to the brain abnormalities related to the condition.  https://medlineplus.gov/genetics/condition/brain-lung-thyroid-syndrome

Clinical features

From HPO
Anxiety
MedGen UID:
1613
Concept ID:
C0003467
Finding
Intense feelings of nervousness, tension, or panic often arise in response to interpersonal stresses. There is worry about the negative effects of past unpleasant experiences and future negative possibilities. Individuals may feel fearful, apprehensive, or threatened by uncertainty, and they may also have fears of falling apart or losing control.
Chorea
MedGen UID:
3420
Concept ID:
C0008489
Disease or Syndrome
Chorea (Greek for 'dance') refers to widespread arrhythmic involuntary movements of a forcible, jerky and restless fashion. It is a random-appearing sequence of one or more discrete involuntary movements or movement fragments. Movements appear random because of variability in timing, duration or location. Each movement may have a distinct start and end. However, movements may be strung together and thus may appear to flow randomly from one muscle group to another. Chorea can involve the trunk, neck, face, tongue, and extremities.
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Dementia
MedGen UID:
99229
Concept ID:
C0497327
Mental or Behavioral Dysfunction
A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Frequent falls
MedGen UID:
163408
Concept ID:
C0850703
Finding

Professional guidelines

PubMed

Paucar M, Laffita-Mesa J, Niemelä V, Malmgren H, Nennesmo I, Lagerstedt-Robinson K, Nordenskjöld M, Svenningsson P
J Neurol Sci 2023 Aug 15;451:120707. Epub 2023 Jun 10 doi: 10.1016/j.jns.2023.120707. PMID: 37379724
Cardoso F
Neurodegener Dis Manag 2014;4(1):67-72. doi: 10.2217/nmt.13.78. PMID: 24640980
Wild EJ, Tabrizi SJ
Pract Neurol 2007 Nov;7(6):360-73. doi: 10.1136/pn.2007.134585. PMID: 18024776

Recent clinical studies

Etiology

Iodice A, Carecchio M, Zorzi G, Garavaglia B, Spagnoli C, Salerno GG, Frattini D, Mencacci NE, Invernizzi F, Veneziano L, Mantuano E, Angriman M, Fusco C
Brain Dev 2019 Mar;41(3):250-256. Epub 2018 Oct 21 doi: 10.1016/j.braindev.2018.10.001. PMID: 30352709
Balint B, Bhatia KP
Eur J Neurol 2015 Apr;22(4):610-7. Epub 2015 Jan 29 doi: 10.1111/ene.12650. PMID: 25643588
Peall KJ, Lumsden D, Kneen R, Madhu R, Peake D, Gibbon F, Lewis H, Hedderly T, Meyer E, Robb SA, Lynch B, King MD, Lin JP, Morris HR, Jungbluth H, Kurian MA
Dev Med Child Neurol 2014 Jul;56(7):642-8. Epub 2013 Oct 31 doi: 10.1111/dmcn.12323. PMID: 24171694
Gras D, 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
J Neurol Neurosurg Psychiatry 2012 Oct;83(10):956-62. Epub 2012 Jul 24 doi: 10.1136/jnnp-2012-302505. PMID: 22832740
Schrag A, Quinn NP, Bhatia KP, Marsden CD
Mov Disord 2000 Mar;15(2):280-8. doi: 10.1002/1531-8257(200003)15:2<280::aid-mds1011>3.0.co;2-q. PMID: 10752577

Diagnosis

Termsarasab P
Continuum (Minneap Minn) 2019 Aug;25(4):1001-1035. doi: 10.1212/CON.0000000000000763. PMID: 31356291
Kumar G, Dixon A
Pediatr Neurol 2014 Oct;51(4):532-6. Epub 2014 Jun 8 doi: 10.1016/j.pediatrneurol.2014.06.001. PMID: 25108317
Kleiner-Fisman G
Handb Clin Neurol 2011;100:199-212. doi: 10.1016/B978-0-444-52014-2.00012-4. PMID: 21496579
Wild EJ, Tabrizi SJ
Pract Neurol 2007 Nov;7(6):360-73. doi: 10.1136/pn.2007.134585. PMID: 18024776
Wheeler PG, Weaver DD, Dobyns WB
Pediatr Neurol 1993 Sep-Oct;9(5):337-40. doi: 10.1016/0887-8994(93)90101-h. PMID: 8292207

Therapy

Termsarasab P
Continuum (Minneap Minn) 2019 Aug;25(4):1001-1035. doi: 10.1212/CON.0000000000000763. PMID: 31356291
Iodice A, Carecchio M, Zorzi G, Garavaglia B, Spagnoli C, Salerno GG, Frattini D, Mencacci NE, Invernizzi F, Veneziano L, Mantuano E, Angriman M, Fusco C
Brain Dev 2019 Mar;41(3):250-256. Epub 2018 Oct 21 doi: 10.1016/j.braindev.2018.10.001. PMID: 30352709
Shiohama T, Ohashi H, Shimizu K, Fujii K, Oba D, Takatani T, Kato M, Shimojo N
Brain Dev 2018 Apr;40(4):353-356. Epub 2017 Dec 27 doi: 10.1016/j.braindev.2017.12.008. PMID: 29289388
Gras D, 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
J Neurol Neurosurg Psychiatry 2012 Oct;83(10):956-62. Epub 2012 Jul 24 doi: 10.1136/jnnp-2012-302505. PMID: 22832740
Wild EJ, Tabrizi SJ
Pract Neurol 2007 Nov;7(6):360-73. doi: 10.1136/pn.2007.134585. PMID: 18024776

Prognosis

Chang FC, Westenberger A, Dale RC, Smith M, Pall HS, Perez-Dueñas B, Grattan-Smith P, Ouvrier RA, Mahant N, Hanna BC, Hunter M, Lawson JA, Max C, Sachdev R, Meyer E, Crimmins D, Pryor D, Morris JG, Münchau A, Grozeva D, Carss KJ, Raymond L, Kurian MA, Klein C, Fung VS
Mov Disord 2016 Jul;31(7):1033-40. Epub 2016 Apr 8 doi: 10.1002/mds.26598. PMID: 27061943Free PMC Article
Kumar G, Dixon A
Pediatr Neurol 2014 Oct;51(4):532-6. Epub 2014 Jun 8 doi: 10.1016/j.pediatrneurol.2014.06.001. PMID: 25108317
Gilbert DL
Semin Pediatr Neurol 2009 Jun;16(2):71-6. doi: 10.1016/j.spen.2009.03.009. PMID: 19501334
de Vries BB, Arts WF, Breedveld GJ, Hoogeboom JJ, Niermeijer MF, Heutink P
Am J Hum Genet 2000 Jan;66(1):136-42. doi: 10.1086/302725. PMID: 10631144Free PMC Article
Wheeler PG, Weaver DD, Dobyns WB
Pediatr Neurol 1993 Sep-Oct;9(5):337-40. doi: 10.1016/0887-8994(93)90101-h. PMID: 8292207

Clinical prediction guides

Iodice A, Carecchio M, Zorzi G, Garavaglia B, Spagnoli C, Salerno GG, Frattini D, Mencacci NE, Invernizzi F, Veneziano L, Mantuano E, Angriman M, Fusco C
Brain Dev 2019 Mar;41(3):250-256. Epub 2018 Oct 21 doi: 10.1016/j.braindev.2018.10.001. PMID: 30352709
Invernizzi F, Zorzi G, Legati A, Coppola G, D'Adamo P, Nardocci N, Garavaglia B, Ghezzi D
Eur J Med Genet 2018 Oct;61(10):581-584. Epub 2018 Apr 3 doi: 10.1016/j.ejmg.2018.03.011. PMID: 29621620
Asmus F, Devlin A, Munz M, Zimprich A, Gasser T, Chinnery PF
Mov Disord 2007 Oct 31;22(14):2104-9. doi: 10.1002/mds.21692. PMID: 17702043
Fernandez M, Raskind W, Matsushita M, Wolff J, Lipe H, Bird T
Neurology 2001 Jul 10;57(1):106-10. doi: 10.1212/wnl.57.1.106. PMID: 11445636
de Vries BB, Arts WF, Breedveld GJ, Hoogeboom JJ, Niermeijer MF, Heutink P
Am J Hum Genet 2000 Jan;66(1):136-42. doi: 10.1086/302725. PMID: 10631144Free PMC Article

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