Brain-Lung-Thyroid Syndrome: An Overview

Introduction

Brain-lung-thyroid syndrome is an illness that is seen in the infant stage. As its name suggests, it affects the brain, lungs, and thyroid gland (a butterfly-shaped gland located in the lower part of the neck). A child who suffers from this issue frequently experiences neurological disturbances, hypothyroidism, respiratory illness, and more. Low muscle tone is often observed in this illness and thus affects the affected individual's movement.

What Is Brain-Lung-Thyroid Syndrome?

• Brain-lung-thyroid syndrome is a disorder affecting the individual’s movement. It is seen to affect all three organs, namely the brain, lungs, and thyroid. Around 50 percent of the affected individuals face problems with all three organs, around 30 percent are observed with brain and thyroid problems, and around 10 percent of the affected ones have brain and lung problems. The brain alone affects 10 to 20 percent of people facing the condition. Such cases are sometimes termed isolated benign hereditary chorea. Brain-lung-thyroid syndrome is a rarely occurring disease with no clear prevalence.

• Almost everyone suffering from brain-lung-thyroid syndrome has brain-related movement anomalies. Benign or non-cancerous hereditary chorea is the most usually seen character of the syndrome. This feature is associated with the involuntary jerking movements (chorea) of the face, torso, and limbs, writhing movements (athetosis) of the limbs, and a few other issues with movement. Individuals who deal with brain-lung-thyroid syndrome can face other problems, too, like difficulty in coordinating movements (ataxia), muscle twitches (myoclonus), and involuntary contractions of muscles that result in twisting and repetitive movements (dystonia). The issues with movement frequently start at the age of one approximately, although they can be seen in early infancy or later stages of life as well and are often preceded by weakening of the muscle tone (hypotonia). This can delay the development of walking movement. The movement issues frequently remain stable and can improve further over the course of time. Some affected individuals might also experience difficulties with learning or intellectual disability.

• Thyroid issues are the next most frequently occurring feature of brain-lung-thyroid syndrome. The thyroid gland functions to form hormones that assist in the regulation of a large range of important bodily functions like growth, brain development, and the rate of chemical reactions taking place in the body (metabolism). Many of the individuals who are affected by this syndrome possess low thyroid function from birth (congenital hypothyroidism), which results in lower-than-normal levels of thyroid hormones.

Others might have a milder form termed compensated or subclinical hypothyroidism, in which the thyroid hormone levels lie in the normal value, even though the thyroid is not functioning well. While many people with brain-lung-thyroid syndrome have a normal thyroid, the gland is smaller in size (hypoplastic) or absent (aplastic) in some

of the affected individuals. Although a shortage of thyroid hormones can result in intellectual disability, other neurological problems can also be seen. However, it is unclear whether such issues in individuals with brain-lung-thyroid syndrome are because of hypothyroidism or are caused by brain abnormalities associated with the condition.

Issues with the lung are frequently noted in brain-lung-thyroid syndrome. Some affected newborns possess respiratory distress syndrome, which causes extreme difficulty while breathing and can be fatal in certain cases. Some affected individuals develop widespread damage to the lungs (interstitial lung disease) or scarring of the lungs (pulmonary fibrosis); both of these can also result in causing breathing issues. Lung infections that occur again and again can be concerning or life-threatening and are also observed in people with brain-lung-thyroid syndrome. Individuals who possess brain-lung-thyroid syndrome are at a higher risk of lung cancer than people in the general population.

What Causes Brain-Lung-Thyroid Syndrome?

The brain-lung-thyroid syndrome occurs due to genetic changes taking place that affect the NKX2-1 gene, which instructs for the formation of a protein called homeobox protein Nkx-2.1. This protein acts as a transcription factor so that it can attach to DNA and regulate

the activity (expression) of other genes. By regulating the expression of certain genes

At the time of embryonic development, homeobox protein Nkx-2.1 assists in directing the

development of the brain, lungs, and thyroid gland to enhance normal functioning.

Mutations in or deletion of the NKX2-1 gene result in a reduced amount of

homeobox protein Nkx-2.1 or impair its functioning. As a result, the expression of genes

regulated by homeobox protein Nkx-2.1 is changed, which impedes the usual development and functioning of the brain, lungs, or thyroid gland. Issues with these organs take place because of an underlying benign acquired chorea, respiratory distress syndrome, congenital hypothyroidism, and other associated characteristics of the brain-lung-thyroid syndrome. It cannot be clearly said why all these organs are affected in a few individuals with this syndrome while only one or two are affected in others.

What Are the Symptoms of Brain-Lung-Thyroid Syndrome?

The symptoms of the brain-lung-thyroid syndrome are mainly seen in the organs that it affects primarily. Some of these symptoms are:

• Ataxia (a condition in which muscles lose control).

• Hypothyroidism (a condition with lower levels of thyroid hormone).

• Movement issues.

• Abnormal lung morphology.

• Scarring of the lungs.

• Hypotonia (lowering of muscle tone occurs).

• Dystonia (a condition where increased muscular tone causes fixed abnormal postures).

• Chorea (it is an abnormal involuntary movement disorder).

What Is the Differential Diagnosis of Brain-Lung-Thyroid Syndrome?

The differential diagnoses of brain-lung-thyroid syndrome resemble other kinds of congenital hypothyroidism, other reasons for infant respiratory distress syndrome, acquired forms of surfactant protein deficiency, and some other reasons for chorea.

How Is Brain-Lung-Thyroid Syndrome Managed?

The brain-lung-thyroid syndrome can be managed according to its symptoms. For example, hypothyroidism can be managed by providing life-long substitution with Levothyroxine. Treatment of compensated hypothyroidism or hyper thyrotropinemia should be started in the early stage only. People who have IRDS (infant respiratory distress syndrome) might need mechanical ventilation for up to several weeks. Treatment for the benign hereditary chorea is not definitive yet.

Conclusion

Brain-lung-thyroid syndrome is a disorder that occurs rarely and is seen to affect the individual’s movement. It is seen to affect all three organs, namely the brain, lungs, and thyroid. It shows various symptoms like neurological issues, lung issues like respiratory distress syndrome, movement disorders, etc. It is seen primarily in infancy. The brain-lung-thyroid syndrome can be managed according to its symptoms.