Molecular Pathogenesis of Congenital Hypothyroidism. Review

Authors: E. Al Taji;  M. Zahradníková;  J. Lebl
Authors‘ workplace: Klinika dětí a dorostu 3. LF UK, FN Královské Vinohrady, Praha, přednosta doc. MUDr. J. Lebl, CSc.
Published in: Čes-slov Pediat 2001; (11): 636-644.


The molecular Pathogenesis of congenital hypothyroidism (CH) has already been clarified in several Patients. The known gene defects causing thyroid dysgenesis (mutations of genes encoding transcriptional factors TTF-1, TTF-2 and PAX-8 and mutations of T5H-receptor gene) lead to a broad spectrum of developmental defects of the thyroid gland (athyreosis, hypoPlasia, ectopy, hemithyroid, rudimental gland, cystic malformation). Their expression may be variable even within a single family and some additional organs might be affected (Puhnonary and neurological impairment, Pituitary abnormalities in TTF-1 mutations; cleft IiP, Palate and epiglottis in TTF-2 mutations; renal malformations or cryptorchidism in PAX-8 mutations). A variable Phenotype (normal thyroid, neonatal goitre) is characteristic for mutations of genes responsible for thyroid hormone biosynthesis. Known mutations of genes encoding for thyroid Peroxidase, Pendrin, thyroglobulin and natrium-iodine symporter are inherited in an autosomal recessive fashion. With the exception of Pendred syndrome (accompanied by congenital sensorineural deafness), they are not accompanied by involvement of other organs or systems. A novel view on severity of CH of central origin was opened by the discovery of mutations of R-thyrotropin gene. It can lead to a severe form of central CH. Central CH may also be caused by mutations of transcriptional factors Pit-1, PROP-1 and LHX3 as a Part of combined Pituitary hormone insufficiency. The genes known so far represent Probably ohly a Part of all genes involved in thyroid development, differentiation and function. The others remain to be discovered.

Key words:
congenital hypothyroidism, Pathogenesis, thyroid dysgenesis, dyshormonogenesis, gene mutations

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Neonatology Paediatrics General practitioner for children and adolescents
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