Rare Rheumatology News

Disease Profile

Brain-lung-thyroid syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

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ICD-10

E03.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction; Choreoathetosis-hypothyroidism-neonatal respiratory distress; Choreoathetosis-hypothyroidism-neonatal respiratory distress syndrome;

Categories

Congenital and Genetic Diseases; Endocrine Diseases; Lung Diseases;

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]

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.

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

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.

    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

      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.

          References

          1. Szinnai G. Brain-lung-thyroid syndrome. Orphanet. April 2011; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=209905.
          2. Patel NJ, Jankovic J. NKX2-1-Related Disorders. GeneReviews. February 20, 2014; https://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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4311306/.

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