Table 3

Classification and etiology of congenital hypothyroidism


Primary hypothyroidism

Thyroid dysgenesis: hypothyroidism due to a developmental anomaly

(Thyroid ectopia, athyreosis, hypoplasia, hemiagenesis)

Associated mutations: (these account for only 2% of thyroid dysgenesis cases; 98% unknown)





Thyroid dyshormonogenesis: hypothyroidism due to impaired hormone production

Associated mutations:

Sodium-iodide symporter defect

Thyroid peroxidase defects

Hydrogen peroxide generation defects (DUOX2, DUOXA2 gene mutations)

Pendrin defect (Pendred syndrome)

Thyroglobulin defect

Iodotyrosine deiododinase defect (DEHAL1, SECISBP2 gene mutations)

Resistance to TSH binding or signaling

Associated mutations:

TSH receptor defect

G-protein mutation: pseudohypoparathyroidism type 1a


Central hypothyroidism (syn: Secondary hypothyroidism)

Isolated TSH deficiency (TSH β subunit gene mutation)

Thyrotropin-releasing hormone deficiency

Isolated, pituitary stalk interruption syndrome (PSIS), hypothalamic lesion, e.g. hamartoma

Thyrotropin-releasing hormone resistance

TRH receptor gene mutation

Hypothyroidism due to deficient transcription factors involved in pituitary development or function

HESX1, LHX3, LHX4, PIT1, PROP1 gene mutations


Peripheral hypothyroidism

Resistance to thyroid hormone

Thyroid receptor β mutation

Abnormalities of thyroid hormone transport

Allan-Herndon-Dudley syndrome (monocarboxylase transporter 8 [MCT8] gene mutation)


Syndromic hypothyroidism

Pendred syndrome - (hypothyroidism- deafness - goiter) Pendrin mutation

Bamforth-Lazarus syndrome - (hypothyroidism - cleft palate - spiky hair) TTF-2 mutation

Ectodermal dysplasia - (hypohidrotic - hypothyroidism - ciliary dyskinesia)

Hypothyroidism - (dysmorphism - postaxial polydactyly - intellectual deficit)

Kocher - Deber - Semilange syndrome - (muscular pseudohypertrophy- hypothyroidism)

Benign chorea - hypothyroidism

Choreoathetosis - (hypothyroidism - neonatal respiratory distress) NKX2.1 /TTF-1 mutation

Obesity - colitis - (hypothyroidism - cardiac hypertrophy - developmental delay)


Transient congenital hypothyroidism

Maternal intake of antithyroid drugs

Transplacental passage of maternal TSH receptor blocking antibodies

Maternal and neonatal iodine deficiency or excess

Heterozygous mutations of THOX2 or DUOXA2

Congenital hepatic hemangioma/hemangioendothelioma

Rastogi and LaFranchi Orphanet Journal of Rare Diseases 2010 5:17   doi:10.1186/1750-1172-5-17

Open Data