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Brain-lung-thyroid syndrome
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

Brain-lung-thyroid syndrome

Brain-lung-thyroid syndrome is a rare genetic disorder characterized by a combination of problems affecting the brain, lungs, and thyroid gland, primarily caused by mutations in the NKX2-1 gene.

Overview

Brain-lung-thyroid syndrome is a group of conditions that affect the brain, lungs, and thyroid (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.

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.

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.

Frequency

Brain-lung-thyroid syndrome is a rare disorder; its prevalence is unknown.

Causes

Brain-lung-thyroid syndrome is caused by genetic changes that affect the NKX2-1 gene, which provides instructions for making a protein called homeobox protein Nkx-2.1. This protein functions as a transcription factor, which means it attaches to DNA and controls the activity (expression) of other genes. By regulating the expression of certain genes during embryonic development, homeobox protein Nkx-2.1 helps direct the development of the brain, lungs, and thyroid gland and promotes their normal function. Mutations in or deletion of the NKX2-1 gene lead to a reduction in the amount of homeobox protein Nkx-2.1 or impair its function. As a result, the expression of genes controlled by homeobox protein Nkx-2.1 is altered, which impedes the normal development and function of the brain, lungs, or thyroid gland. Problems with these organs underlie benign hereditary chorea, respiratory distress syndrome, congenital hypothyroidism, and other features of brain-lung-thyroid syndrome. It is unclear why all three organs are affected in some individuals with the condition, while only one or two are affected in others.

Learn more about the gene associated with Brain-lung-thyroid syndrome

  • NKX2-1

Inheritance

This condition is inherited in an autosomal dominant inheritance, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

Other Names

  • BLT syndrome
  • Brain-thyroid-lung syndrome
  • CAHTP
  • Choreoathetosis, hypothyroidism, and neonatal respiratory distress
  • Chreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction

Frequently Asked Questions

When movement abnormalities such as chorea or ataxia are the sole presenting feature, clinicians first perform a detailed neurological exam and brain MRI to rule out other causes. Genetic testing for mutations in the NKX2‑1 gene is then essential; a positive result confirms the diagnosis. Even if lung or thyroid signs are absent, the presence of a pathogenic NKX2‑1 variant together with the characteristic movement disorder establishes brain‑lung‑thyroid syndrome. What respiratory symptoms are typical in this syndrome and how should they be managed in infants?::Infants often have persistent tachypnea, wheezing, and recurrent lower respiratory tract infections. Management includes routine pulmonary function testing, use of bronchodilators (e.g., albuterol) for wheeze, and inhaled corticosteroids if chronic inflammation is present. Severe cases may require supplemental oxygen or, rarely, mechanical ventilation during acute exacerbations. Early referral to a pediatric pulmonologist is recommended. How does thyroid dysfunction present in brain‑lung‑thyroid syndrome, and what monitoring schedule is recommended?::Thyroid abnormalities can be either hypothyroidism or hyperthyroidism. Symptoms include fatigue, weight changes, growth delay, or irritability. Baseline labs should include TSH, free T4, and thyroid antibodies. If hypothyroidism is detected, levothyroxine therapy is started and TSH is checked every 6–8 weeks until stable, then every 6–12 months. If hyperthyroidism occurs, antithyroid medication or beta‑blockers may be needed, with labs monitored similarly. Are there specific medications that can help control the chorea or ataxia associated with the condition?::Yes. Tetrabenazine or deutetrabenazine can reduce chorea by depleting monoamine neurotransmitters. For ataxia or dystonia, low‑dose antipsychotics (e.g., risperidone) or benzodiazepines (e.g., clonazepam) may provide benefit. Physical therapy focusing on balance and coordination is also crucial. Medication choice should be individualized, and side‑effect monitoring is essential, especially in children.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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