SNP Shot: Genomic Insights

Brain-lung-thyroid syndrome encompasses a group of conditions affecting the brain, lungs, and thyroid gland (located in the lower neck). While traditionally defined by issues in all three organs, the term now describes various combinations of problems in these areas. Approximately half of those affected experience issues in all three organs, roughly 30% have brain and thyroid problems, and about 10% have brain and lung problems. In 10-20% of cases, only the brain is affected; these cases are sometimes termed isolated benign hereditary chorea.

Movement abnormalities related to the brain are almost universal in individuals with brain-lung-thyroid syndrome. The most common of these is benign hereditary chorea, characterized by involuntary jerking movements (chorea) of the face, torso, and limbs, as well as writhing movements (athetosis) of the limbs, and other movement disorders. Additional abnormalities can include impaired coordination (ataxia), muscle twitches (myoclonus), and involuntary muscle contractions causing twisting and repetitive movements (dystonia). These movement problems often begin around age 1, though they can manifest earlier or later, frequently preceded by weak muscle tone (hypotonia). While these movement problems can delay walking development, they generally stabilize and may improve over time. Some individuals also experience learning difficulties or intellectual disability.

Thyroid problems are the second most prevalent feature of brain-lung-thyroid syndrome. The thyroid produces hormones vital for regulating growth, brain development, metabolism, and other bodily functions. Many affected individuals have congenital hypothyroidism (reduced thyroid function from birth), leading to lower-than-normal thyroid hormone levels. Others have subclinical hypothyroidism, a milder condition where hormone levels are normal despite improper thyroid function. Although most individuals have a normal-sized thyroid gland, some have a gland that is smaller than normal (hypoplastic) or absent (aplastic). While thyroid hormone deficiency can cause intellectual disability and neurological problems, it is unclear if these issues in brain-lung-thyroid syndrome are a direct result of hypothyroidism or related to brain abnormalities associated with the condition.

Lung problems are also frequently observed in brain-lung-thyroid syndrome. Some newborns experience respiratory distress syndrome, causing severe breathing difficulties that can be life-threatening. Others may develop widespread lung damage (interstitial lung disease) or lung scarring (pulmonary fibrosis), both of which can also lead to breathing problems. Recurrent and potentially life-threatening lung infections are also common. Furthermore, individuals with brain-lung-thyroid syndrome have an increased risk of developing lung cancer compared to the general population.

Inheritance:

Brain-lung-thyroid syndrome is inherited in an autosomal dominant manner, meaning that only one copy of the mutated gene is necessary to cause the disorder. In some instances, a person inherits the mutation from an affected parent. In other cases, the condition arises from a new mutation in the gene, occurring in individuals with no family history of the disorder.