SLC26A4-related sensorineural hearing loss (SLC26A4-SNHL), characterized by inner ear malformations also associated with vestibular dysfunction, comprises two phenotypes: (1) nonsyndromic SLC26A4-SNHL (also referred to as DFNB4 or nonsyndromic enlargement of the vestibular aqueduct [NSEVA]) and (2) Pendred syndrome (PDS) that includes thyroid involvement (typically identified more frequently in countries without universal salt iodization programs). The time of onset and type of presentation of the SNHL vary (such that some newborns pass their newborn hearing screening); however, by age three years most children have bilateral and severe-to-profound hearing loss. Manifestations of vestibular dysfunction (such as head-tilting, vomiting, and/or delayed ambulation or clumsiness in a child who previously walked well) can precede or accompany the fluctuations in hearing typical of this disorder. Thyroid enlargement (goiter) occurs gradually and is typically evident in the second decade, especially if iodine is not routinely included in the diet.

Kanou et al. (2007) reviewed characteristics of thyroid dyshormonogenesis caused by mutations in the thyroglobulin (TG) gene. This form of thyroid dyshormonogenesis has an estimated prevalence of one in 100,000 newborns. Inherited in an autosomal recessive manner, the disorder in the majority of patients causes large goiters of elastic and soft consistency. Although the degree of thyroid dysfunction varies considerably among patients with defective TG synthesis, patients usually have a relatively high serum free T3 concentration with disproportionately low free T4 level. The maintenance of relatively high FT3 levels prevents profound tissue hypothyroidism except in brain and pituitary, which are dependent on T4 supply, resulting in neurologic and intellectual defects in some cases.

NKX2-1-related disorders range from benign hereditary chorea (BHC) to choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress syndrome (also known as brain-lung-thyroid syndrome). Childhood-onset chorea, the hallmark feature of NKX2-1-related disorders, may or may not be associated with pulmonary disease or congenital hypothyroidism. Age of onset of chorea varies from early infancy (most commonly) to late childhood or adolescence and may progress into the second decade, after which it remains static or (rarely) remits. Pulmonary disease, the second most common manifestation, can include respiratory distress syndrome in neonates, interstitial lung disease in young children, and pulmonary fibrosis in older individuals. The risk for pulmonary carcinoma is increased in young adults with NKX2-1-related disorders. Thyroid dysfunction, occurring as a result of thyroid dysgenesis, can present as congenital or compensated hypothyroidism. In one review, 50% of affected individuals had the full brain-lung-thyroid syndrome, 30% had brain and thyroid involvement only, and 13% had chorea only.

A rare, autosomal recessive inherited disorder usually caused by mutations in the THRB gene. It is characterized by a defective physiological resistance to thyroid hormones, resulting in the elevation of thyroxin and triiodothyronine in the serum.