Brain-lung-thyroid syndrome

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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:

Congenital and Genetic Diseases; Endocrine Diseases; Lung Diseases; Congenital and Genetic Diseases; Endocrine Diseases; Lung Diseases; Nervous System Diseases See More

Summary Summary

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

Symptoms Symptoms

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.

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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
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 dysgenesis		0008188
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

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 2/1/2021

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Inheritance Inheritance

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

Diagnosis Diagnosis

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.

Find a Specialist Find a Specialist

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

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from MedlinePlus Genetics.

Related Diseases Related Diseases

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.

Organizations Organizations

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

Children's Interstitial Lung Disease Foundation
6539 Harrison Ave #1045
Cincinnati, OH 45247
E-mail: info@child-foundation.org
Website: http://child-foundation.org/
The MAGIC Foundation
4200 Cantera Dr. #106
Warrenville, IL 60555
Toll-free: 800-362-4423
Telephone: 630-836-8200
Fax: 630-836-8181
E-mail: contactus@magicfoundation.org
Website: https://www.magicfoundation.org/

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Learn More Learn More

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.

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References References

Szinnai G. Brain-lung-thyroid syndrome. Orphanet. April 2011; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=209905.
Patel NJ, Jankovic J. NKX2-1-Related Disorders. GeneReviews. February 20, 2014; http://www.ncbi.nlm.nih.gov/books/NBK185066/.
NKX2-1. Genetics Home Reference (GHR). March 7, 2016; https://ghr.nlm.nih.gov/gene/NKX2-1.
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/.