Brain-lung-thyroid syndrome

Title

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

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Asthma	5%
Congenital septal defect	5%
Sleep disturbance	5%
Ataxia	-
Autosomal dominant inheritance	-
Choreoathetosis	-
Compensated hypothyroidism	-
Congenital hypothyroidism	-
Congenital onset	-
Difficulty walking	-
Dysarthria	-
Dystonia	-
Motor delay	-
Muscular hypotonia	-
Neonatal respiratory distress	-
Recurrent respiratory infections	-
Respiratory distress	-
Thyroid-stimulating hormone excess	-

Last updated: 10/1/2016

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.

Treatment Treatment

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

Management Guidelines

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.

Do you have updated information on this condition? Let us know.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics 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 GeneTests, 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 Genetics Home Reference.

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.

In-Depth Information

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.

GARD Answers GARD Answers

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.

Have a question? Contact a GARD Information Specialist.

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/.