Congenital hypothyroidism results in inadequate thyroid hormone production in newborn infants. The cause of this disease in 80 to 85% of cases is due either to the absence, abnormal location or reduced size of the thyroid gland. In the remaining few cases, decreased production of the hormone from a normal thyroid gland causes the disease. Infants that are hypothyroidic show the following symptoms: puffy appearing face, dull look, dry and brittle hair, large tongue protruding from the mouth, sluggishness, lack of interest in nursing, excessive sleepiness, early and prolonged jaundice, difficult respirations and apnea spells, and constipation. Often, there is an involvement of umbilical hernia. The most serious effect of untreated congenital hypothyroidism is mental retardation. Absolute arrest of linear growth and bone maturation may also occur. If left untreated, neurological complications, such as spasticity and gait abnormalities, dysarthria or mutism, and autistic behavior may develop.
Incidence of congenital hypothyroidism ranges between 1 in 3,500-4,000 live births. Diadnosis is made through newborn screening, which analyzes thyroid stimulating hormone (TSH) and/or thyroxine (T4) levels. Replacement therapy with thyroxine is the standard treatment. Prognosis for the patients is very good, if the disorder is detected within the first few weeks.
There are several genes responsible for congenital hypothyroidism. Mutations in the Paired Box Gene 8 (PAX8) and the Thyroid-Stimulating Hormone Receptor (TSHR) gene cause the disease by preventing the development of the thyroid gland. On the other hand, genes like Dual Oxidase 2 (DUOX2), Solute Carrier Family 5 (SLC5A5), Thyroglobulin (TG), Thyroid Peroxidase (TPO), and Thyroid-Stimulating Hormone, Beta Chain (TSHB) play important roles in the production of the thyroid hormone.