Central Congenital Hypothyroidism

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Retrieved

2021-01-23

Source

Orphanet

Trials

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Genes

TSHB, SLC30A10, TRHR, POU1F1, POMC, PROP1, LHX3, HESX1, LHX4, CDH23, RBM28, SUFU, ARNT2, POU3F4, TMEM67, SOX3, SOX2, SMARCB1, PRL, HJV, AIP, BRAF, PDGFB, MEN1, CTNNB1, GH1, GLI2, GLI3, LEPR, LEP

TSHB, SLC30A10, TRHR, POU1F1, POMC, PROP1, LHX3, HESX1, LHX4, CDH23, RBM28, SUFU, ARNT2, POU3F4, TMEM67, SOX3, SOX2, SMARCB1, PRL, HJV, AIP, BRAF, PDGFB, MEN1, CTNNB1, GH1, GLI2, GLI3, LEPR, LEP, SOX2-OT, NF2, PCSK1, OTX2, SLC20A1, IGSF1, SOD1, ACE, ELN, GHRHR, TNF, TRH, GTF2IRD1, IGHD, CDKN1C, SST, GTF2I

Drugs

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Central or secondary congenital hypothyroidism is a type of permanent congenital hypothyroidism (see this term) characterized by permanent thyroid hormone deficiency that is present from birth and secondary to a disorder in the thyroid-stimulating hormone (TSH) - thyrotropin-releasing hormone (TRH) system.

Epidemiology

Prevalence is unknown.

Clinical description

The clinical manifestations are often subtle, probably as a result of trans-placental passage of some maternal thyroid hormone or due to the fact that many infants have some thyroid production of their own. More specific symptoms and signs often do not develop until several months of age. Common clinical features and signs include decreased activity and increased sleep, feeding difficulty and constipation, prolonged jaundice, myxedematous facies, large fontanels (especially posterior), macroglossia, a distended abdomen with umbilical hernia, and hypotonia. Goiter is always absent. Slow linear growth and developmental delay are usually apparent by 4-6 months of age. Without treatment central hypothyroidism results in intellectual deficit and short stature.

Etiology

Central hypothyroidism usually results from defects of TSH production and is often part of a disorder causing congenital hypopituitarism (see this term), in which case the clinical signs may also include septo-optic dysplasia or cleft lip and/or palate as well as other signs of hypopituitarism, or part of a larger genetic syndrome such as pituitary stalk interruption syndrome (see this term). Mutations in genes regulating pituitary gland development including HESX1, LHX3, LHX4, POU1F1 and PROP1 (3p21.2-p21.1, 9q34.3, 1q25, 3p11 and 5q) may also cause central hypothyroidism. Central hypothyroidism may also result from isolated TSH deficiency (see this term), which is transmitted in an autosomal recessive manner and is caused by mutations in the TSHB subunit gene (1p13), or from TRH resistance (see this term) caused by mutations in the TRH receptor gene (TRHR; 8q23).