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Isolated thyroid-stimulating hormone deficiency(CHNG4)

MedGen UID:
Concept ID:
Disease or Syndrome
Synonyms: Hypothryoidism, congenital, nongoitrous 4; Pituitary cretinism; THYROID-STIMULATING HORMONE DEFICIENCY; Thyroid-stimulating hormone, deficiency of; Thyrotropin deficiency, isolated; TSH deficiency
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
Concept ID:
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Gene (location): TSHB (1p13.2)
Monarch Initiative: MONDO:0010139
OMIM®: 275100
Orphanet: ORPHA90674


A type of central congenital hypothyroidism, a permanent thyroid deficiency that is present from birth, characterized by low levels of thyroid hormones due to a deficiency in TSH synthesis. [from ORDO]

Clinical features

From HPO
Severe postnatal growth retardation
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Severely slow or limited growth after birth, being four standard deviations or more below age- and sex-related norms.
Intellectual disability, severe
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Mental or Behavioral Dysfunction
Severe mental retardation is defined as an intelligence quotient (IQ) in the range of 20-34.
Intellectual disability, progressive
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Concept ID:
Mental or Behavioral Dysfunction
The term progressive intellectual disability should be used if intelligence decreases/deteriorates over time.
Umbilical hernia
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Anatomical Abnormality
Protrusion of abdominal contents through a defect in the abdominal wall musculature around the umbilicus. Skin and subcutaneous tissue overlie the defect.
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Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Congenital omphalocele
MedGen UID:
Concept ID:
Congenital Abnormality
An omphalocele is an abdominal wall defect limited to an open umbilical ring, and is characterized by the herniation of membrane-covered internal organs into the open base of the umbilical cord. Omphalocele is distinguished from gastroschisis (230750), in which the abdominal wall defect is located laterally to a normally closed umbilical ring with herniation of organs that are uncovered by membranes (summary by Bugge, 2010). On the basis of clinical manifestations, epidemiologic characteristics, and the presence of additional malformations, Yang et al. (1992) concluded that omphalocele and gastroschisis are casually and pathogenetically distinct abdominal wall defects. Omphalocele can be a feature of genetic disorders, such as Beckwith-Wiedemann syndrome (130650) and the Shprintzen-Goldberg syndrome (182210).
Generalized hypotonia
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Concept ID:
Generalized muscular hypotonia (abnormally low muscle tone).
Wide anterior fontanel
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Concept ID:
Enlargement of the anterior fontanelle with respect to age-dependent norms.
Abnormality of metabolism/homeostasis
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Concept ID:
Hoarse cry
MedGen UID:
Concept ID:
MedGen UID:
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Disease or Syndrome
Increased length and width of the tongue.
Depressed nasal bridge
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Concept ID:
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Congenital hypothyroidism
MedGen UID:
Concept ID:
Disease or Syndrome
Congenital hypothyroidism is a partial or complete loss of function of the thyroid gland (hypothyroidism) that affects infants from birth (congenital). The thyroid gland is a butterfly-shaped tissue in the lower neck. It makes iodine-containing hormones that play an important role in regulating growth, brain development, and the rate of chemical reactions in the body (metabolism). People with congenital hypothyroidism have lower-than-normal levels of these important hormones.\n\nCongenital hypothyroidism can also occur as part of syndromes that affect other organs and tissues in the body. These forms of the condition are described as syndromic. Some common forms of syndromic hypothyroidism include Pendred syndrome, Bamforth-Lazarus syndrome, and brain-lung-thyroid syndrome.\n\nCongenital hypothyroidism occurs when the thyroid gland fails to develop or function properly. In 80 to 85 percent of cases, the thyroid gland is absent, severely reduced in size (hypoplastic), or abnormally located. These cases are classified as thyroid dysgenesis. In the remainder of cases, a normal-sized or enlarged thyroid gland (goiter) is present, but production of thyroid hormones is decreased or absent. Most of these cases occur when one of several steps in the hormone synthesis process is impaired; these cases are classified as thyroid dyshormonogenesis. Less commonly, reduction or absence of thyroid hormone production is caused by impaired stimulation of the production process (which is normally done by a structure at the base of the brain called the pituitary gland), even though the process itself is unimpaired. These cases are classified as central (or pituitary) hypothyroidism.\n\nSigns and symptoms of congenital hypothyroidism result from the shortage of thyroid hormones. Affected babies may show no features of the condition, although some babies with congenital hypothyroidism are less active and sleep more than normal. They may have difficulty feeding and experience constipation. If untreated, congenital hypothyroidism can lead to intellectual disability and slow growth. In the United States and many other countries, all hospitals test newborns for congenital hypothyroidism. If treatment begins in the first two weeks after birth, infants usually develop normally.

Term Hierarchy

Follow this link to review classifications for Isolated thyroid-stimulating hormone deficiency in Orphanet.

Professional guidelines


Lauffer P, Zwaveling-Soonawala N, Naafs JC, Boelen A, van Trotsenburg ASP
Front Endocrinol (Lausanne) 2021;12:686317. Epub 2021 Sep 9 doi: 10.3389/fendo.2021.686317. PMID: 34566885Free PMC Article
Mateo RCI, Hennessey JV
Endocrine 2019 Oct;66(1):10-17. Epub 2019 Jul 18 doi: 10.1007/s12020-019-02006-8. PMID: 31321670Free PMC Article
Huchon C, Deffieux X, Beucher G, Capmas P, Carcopino X, Costedoat-Chalumeau N, Delabaere A, Gallot V, Iraola E, Lavoue V, Legendre G, Lejeune-Saada V, Leveque J, Nedellec S, Nizard J, Quibel T, Subtil D, Vialard F, Lemery D; Collège National des Gynécologues Obstétriciens Français
Eur J Obstet Gynecol Reprod Biol 2016 Jun;201:18-26. Epub 2016 Mar 18 doi: 10.1016/j.ejogrb.2016.02.015. PMID: 27039249

Recent clinical studies

Clinical prediction guides

Labbe A, Dubray C, Gaillard G, Besse G, Assali P, Malpuech G
Clin Pediatr (Phila) 1984 Dec;23(12):675-8. doi: 10.1177/000992288402301202. PMID: 6437722

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