National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Brain-lung-thyroid syndrome


Other Names:
Choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction; Choreoathetosis-hypothyroidism-neonatal respiratory distress; Choreoathetosis-hypothyroidism-neonatal respiratory distress syndrome; Choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction; Choreoathetosis-hypothyroidism-neonatal respiratory distress; Choreoathetosis-hypothyroidism-neonatal respiratory distress syndrome; CAHTP; BLT syndrome See More
Categories:
Brain-lung-thyroid syndrome is a rare movement disorder that begins in infancy with neurological disturbances, hypothyroidism, and respiratory problems.[1][2][3] It is characterized by low muscle tone (hypotonia) which evolves into benign hereditary chorea and ataxia, neonatal respiratory distress syndrome and/or interstitial lung disease, and congenital hypothyroidism.[1][2][3][4] The scope and severity of symptoms varies widely, even within families.[1][2] Treatment may include tetrabenazine and levodopa for chorea and thyroid replacement therapy for hypothyroidism. Respiratory distress symptoms and interstitial lung disease should be treated as needed.[2] Brain-lung-thyroid syndrome is caused by mutations in the NKX2-1 gene. It is passed through families in an autosomal dominant fashion.[1][2][3]

Brain-lung-thyroid syndrome represents the most severe expression of the NKX2-1-related disorders, with benign hereditary chorea at the milder end of the spectrum.[1][2]
Last updated: 3/14/2016

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 57 |
Medical Terms Other Names
Learn More:
HPO ID
30%-79% of people have these symptoms
Ataxia 0001251
Choreoathetosis 0001266
Congenital hypothyroidism
Underactive thyroid gland from birth
0000851
Infantile muscular hypotonia
Decreased muscle tone in infant
0008947
Neonatal respiratory distress
Infantile respiratory distress
Newborn respiratory distress
Respiratory distress, neonatal
[ more ] 		0002643
Respiratory distress
Breathing difficulties
Difficulty breathing
[ more ] 		0002098
5%-29% of people have these symptoms
Abnormal cardiac septum morphology 0001671
Apraxia 0002186
Asthma 0002099
Clumsiness 0002312
Compensated hypothyroidism 0008223
Dysarthria
Difficulty articulating speech
0001260
Dystonia 0001332
Failure to thrive
Faltering weight
Weight faltering
[ more ] 		0001508
Global developmental delay 0001263
Increased thyroid-stimulating hormone level 0002925
Intellectual disability, mild
Mental retardation, borderline-mild
Mild and nonprogressive mental retardation
Mild mental retardation
[ more ] 		0001256
Intention tremor 0002080
Interstitial pulmonary abnormality
Abnormality in area between air sacs in lung
0006530
Motor delay 0001270
Myoclonus 0001336
Pulmonary arterial hypertension
Increased blood pressure in blood vessels of lungs
0002092
Recurrent pneumonia 0006532
Sensorineural hearing impairment 0000407
Sleep disturbance
Trouble sleeping
Difficulty sleeping
[ more ] 		0002360
Thyroid hemiagenesis 0011780
Ventricular septal defect
Hole in heart wall separating two lower heart chambers
0001629
1%-4% of people have these symptoms
Abnormal drinking behavior 0030082
Abnormal eating behavior 0100738
Abnormal facial shape
Unusual facial appearance
0001999
Abnormality of the sella turcica 0002679
Agenesis of corpus callosum 0001274
Cavum septum pellucidum 0002389
Falls 0002527
Hyperactivity
More active than typical
0000752
Hypodontia
Failure of development of between one and six teeth
0000668
Hypoparathyroidism
Decreased parathyroid hormone secretion
0000829
Hypospadias 0000047
Megacystis 0000021
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] 		0000252
Obsessive-compulsive behavior
Obsessive compulsive behavior
0000722
Patent foramen ovale 0001655
Pulmonary fibrosis 0002206
Respiratory failure 0002878
Schizophrenia 0100753
Short attention span
Poor attention span
Problem paying attention
[ more ] 		0000736
Short stature
Decreased body height
Small stature
[ more ] 		0004322
Unexplained fevers 0001955
Vesicoureteral reflux 0000076
Webbed neck
Neck webbing
0000465
Percent of people who have these symptoms is not available through HPO
Atrial septal defect
An opening in the wall separating the top two chambers of the heart
Hole in heart wall separating two upper heart chambers
[ more ] 		0001631
Autosomal dominant inheritance 0000006
Congenital onset
Symptoms present at birth
0003577
Difficulty walking
Difficulty in walking
0002355
Generalized hypotonia
Decreased muscle tone
Low muscle tone
[ more ] 		0001290
Muscular hypotonia
Low or weak muscle tone
0001252
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections
[ more ] 		0002205
Showing of 57 |
Last updated: 7/1/2020
Brain-lung-thyroid syndrome is inherited in an autosomal dominant manner, which means that one copy of the altered gene in each cell is sufficient to cause the disorder.[1][2] Most affected individuals inherit the altered gene from an affected parent. Each child of an individual with brain-lung-thyroid syndrome has a 50% chance of inheriting the altered gene.[2] 
Last updated: 3/14/2016

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include other forms of congenital hypothyroidism, other causes of infant respiratory distress syndrome, genetic forms of surfactant protein deficiency, and other causes of chorea.
Visit the Orphanet disease page for more information.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Brain-lung-thyroid syndrome. This website is maintained by the National Library of Medicine.

In-Depth Information

  • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Brain-lung-thyroid syndrome. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. Szinnai G. Brain-lung-thyroid syndrome. Orphanet. April 2011; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=209905.
  2. Patel NJ, Jankovic J. NKX2-1-Related Disorders. GeneReviews. February 20, 2014; http://www.ncbi.nlm.nih.gov/books/NBK185066/.
  3. NKX2-1. Genetics Home Reference (GHR). March 7, 2016; https://ghr.nlm.nih.gov/gene/NKX2-1.
  4. de Filippis T, Marelli F, Vigone MC, Di Frenna M, Weber G, Persani L. Novel NKX2-1 Frameshift Mutations in Patients with Atypical Phenotypes of the Brain-Lung-Thyroid Syndrome. Eur Thyroid J. 2014 Dec; 2(4):227-33. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4311306/.