There is a slightly higher risk of developing both lung and thyroid cancer, but it is yet to be precisely determined.
In addition, clinical manifestations of NKX2-1 syndrome may vary in severity. Both the full presentation involving all three organs (brain-lung-thyroid syndrome) as well as an isolated manifestation involving only one or two of these organs are possible. Complete brain-lung-thyroid syndrome occurs in approximately 50% of patients with an NKX2-1 mutation, with 30% of patients exhibiting symptoms affecting the brain and thyroid gland and 13% of patients exhibiting isolated chorea.
Chorea is characterized by involuntary, irregular, and jerky movements and typically occurs for the first time in early infancy, at the end of the first year of life, or in late childhood to early adolescence. Chorea is progressive until the second decade of life, after which it usually stagnates or even exhibits regressive tendencies.
In addition to chorea, other neurological abnormalities associated with an NKX2-1 mutation are also described, such as intention tremor (trembling when approaching a target), speech disorders and disorders of arbitrary facial expression, hearing loss, muscular weakness, decreased coordination, motor developmental delays, muscle twitching, and movement coordination disorders.
After chorea, respiratory disorders are the second most common manifestation associated with an NKX2-1 mutation and are described in approximately 50% of patients, with varying degrees of severity. The following diseases may occur:
Thyroid dysfunction as part of NKX2-1 syndrome is caused by a malformation and can manifest as congenital hypothyroidism, reduced or absent production of the thyroid hormone, or compensated hypothyroidism (low to normal thyroid hormone and elevated TSH (thyroid-stimulating hormone)), whereby the thyroid may be smaller in size or completely absent.