SNP Shot: Genomic Insights

Congenital hypothyroidism is a condition present at birth where an infant's thyroid gland doesn't function properly, leading to insufficient thyroid hormone production. The thyroid, a butterfly-shaped gland in the lower neck, uses iodine to create hormones crucial for regulating growth, brain development, and metabolism. Babies with congenital hypothyroidism have lower levels of these essential hormones.

This condition arises from either a failure of the thyroid gland to develop correctly or a malfunction in its function. In the majority of cases (80-85%), the thyroid is either absent, significantly underdeveloped (hypoplastic), or located in an abnormal position. These situations are categorized as thyroid dysgenesis. In the remaining cases, the thyroid gland may be normal-sized or even enlarged (goiter), but it still fails to produce enough thyroid hormones. Most of these instances involve problems within the hormone synthesis process, classified as thyroid dyshormonogenesis. Less frequently, the issue stems from inadequate stimulation of the thyroid hormone production process by the pituitary gland at the base of the brain, even if the thyroid itself is capable of normal function. This is termed central (or pituitary) hypothyroidism.

The signs and symptoms of congenital hypothyroidism are a direct result of the hormone deficiency. Some affected infants may not display any noticeable signs. However, others might be less active, sleep more than usual, experience feeding difficulties, or suffer from constipation. Without treatment, congenital hypothyroidism can lead to intellectual disability and impaired growth. Newborn screening for this condition is standard practice in hospitals across the United States and many other countries. Early treatment, initiated within the first two weeks of life, typically allows infants to develop normally.

Congenital hypothyroidism can also be a component of broader syndromes affecting multiple organs and tissues. These are known as syndromic forms, and examples include Pendred syndrome, Bamforth-Lazarus syndrome, and brain-lung-thyroid syndrome.

Inheritance:

In most instances, congenital hypothyroidism occurs sporadically, meaning it appears in individuals without a family history of the disorder.

When the condition is inherited, it commonly follows an autosomal recessive inheritance pattern. This means that both copies of the relevant gene within each cell must have mutations for the condition to manifest. Parents of a child with an autosomal recessive condition typically each carry one copy of the mutated gene but don't exhibit any signs or symptoms themselves.

Congenital hypothyroidism resulting from mutations in the PAX8, TSHR or DUOX2 genes can be inherited in an autosomal dominant manner. In this case, only one copy of the altered gene in each cell is enough to cause the disorder. An affected individual may inherit the mutation from a parent who also has the condition. In other instances, the mutation arises spontaneously (de novo) during the formation of eggs or sperm, or in early embryonic development. These spontaneous cases occur in individuals with no prior family history of the disorder.