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Hypothyroidism, congenital, nongoitrous, 2(CHNG2)

MedGen UID:
358389
Concept ID:
C1869118
Congenital Abnormality
Synonyms: CHNG2; Hypothyroidism, congenital, due to thyroid dysgenesis or hypoplasia
 
Gene (location): PAX8 (2q14.1)
 
Monarch Initiative: MONDO:0024264
OMIM®: 218700

Definition

Congenital 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.

Signs 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.

Congenital 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.

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. [from MedlinePlus Genetics]

Clinical features

From HPO
Bradycardia
MedGen UID:
140901
Concept ID:
C0428977
Finding
A slower than normal heart rate (in adults, slower than 60 beats per minute).
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Abdominal distention
MedGen UID:
34
Concept ID:
C0000731
Finding
Distention of the abdomen.
Constipation
MedGen UID:
1101
Concept ID:
C0009806
Sign or Symptom
Infrequent or difficult evacuation of feces.
Feeding difficulties in infancy
MedGen UID:
436211
Concept ID:
C2674608
Finding
Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.
Lethargy
MedGen UID:
7310
Concept ID:
C0023380
Sign or Symptom
A state of fatigue, either physical or mental slowness and sluggishness, with difficulties in initiating or performing simple tasks. Distinguished from apathy which implies indifference and a lack of desire or interest in the task. A person with lethargy may have the desire, but not the energy to engage in personal or socially relevant tasks.
Umbilical hernia
MedGen UID:
9232
Concept ID:
C0019322
Anatomical Abnormality
Protrusion of abdominal contents through a defect in the abdominal wall musculature around the umbilicus. Skin and subcutaneous tissue overlie the defect.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
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.
Delayed skeletal maturation
MedGen UID:
108148
Concept ID:
C0541764
Finding
A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
Large posterior fontanelle
MedGen UID:
340819
Concept ID:
C1855233
Finding
An enlargement of the posterior fontanelle relative to age-dependent norms.
Stridor
MedGen UID:
11613
Concept ID:
C0038450
Sign or Symptom
Stridor is a high pitched sound resulting from turbulent air flow in the upper airway.
Hypothermia
MedGen UID:
5720
Concept ID:
C0020672
Finding
Reduced body temperature due to failed thermoregulation.
Hyperbilirubinemia
MedGen UID:
86321
Concept ID:
C0311468
Finding
An increased amount of bilirubin in the blood.
Increased circulating thyroglobulin concentration
MedGen UID:
1375023
Concept ID:
C4476805
Finding
An abnormal elevation of the concentration of thyroglobulin, a protein produced in the thyroid gland that acts as a precursor to thyrroid hormones.
Hoarse cry
MedGen UID:
394791
Concept ID:
C2678303
Finding
Macroglossia
MedGen UID:
44236
Concept ID:
C0024421
Disease or Syndrome
Increased length and width of the tongue.
Dry skin
MedGen UID:
56250
Concept ID:
C0151908
Sign or Symptom
Skin characterized by the lack of natural or normal moisture.
Congenital hypothyroidism
MedGen UID:
41344
Concept ID:
C0010308
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\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.\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\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.
Goiter
MedGen UID:
42270
Concept ID:
C0018021
Disease or Syndrome
An enlargement of the thyroid gland.
Hypothyroidism
MedGen UID:
6991
Concept ID:
C0020676
Disease or Syndrome
Deficiency of thyroid hormone.
Thyroid hypoplasia
MedGen UID:
57720
Concept ID:
C0151516
Disease or Syndrome
Developmental hypoplasia of the thyroid gland.
Ectopic thyroid
MedGen UID:
78591
Concept ID:
C0266283
Congenital Abnormality
Mislocalised thyroid gland.
Elevated circulating thyroid-stimulating hormone concentration
MedGen UID:
108325
Concept ID:
C0586553
Finding
Increased concentration of thyroid-stimulating hormone (TSH) in the blood circulation.
Thyroid agenesis
MedGen UID:
155447
Concept ID:
C0749420
Congenital Abnormality
The congenital absence of the thyroid gland.
Decreased circulating T4 concentration
MedGen UID:
1611997
Concept ID:
C4531078
Finding
A reduction below the normal concentration of thyroxine in the blood. Thyroxine (also known as T4) is the main hormone secreted by the thyroid gland into the blood. It can be converted into the active form triiodothyronine (also known as T3).

Term Hierarchy

Recent clinical studies

Etiology

Gullo D, Latina A, Frasca F, Squatrito S, Belfiore A, Vigneri R
Clin Endocrinol (Oxf) 2017 Aug;87(2):207-215. Epub 2017 May 16 doi: 10.1111/cen.13351. PMID: 28398655
Bagattini B, Cosmo CD, Montanelli L, Piaggi P, Ciampi M, Agretti P, Marco GD, Vitti P, Tonacchera M
Eur J Endocrinol 2014 Nov;171(5):615-21. doi: 10.1530/EJE-14-0621. PMID: 25305309

Diagnosis

McGrath N, Hawkes CP, Ryan S, Mayne P, Murphy N
Horm Res Paediatr 2021;94(1-2):36-43. Epub 2021 May 27 doi: 10.1159/000514989. PMID: 34044405

Therapy

Gullo D, Latina A, Frasca F, Squatrito S, Belfiore A, Vigneri R
Clin Endocrinol (Oxf) 2017 Aug;87(2):207-215. Epub 2017 May 16 doi: 10.1111/cen.13351. PMID: 28398655
Bagattini B, Cosmo CD, Montanelli L, Piaggi P, Ciampi M, Agretti P, Marco GD, Vitti P, Tonacchera M
Eur J Endocrinol 2014 Nov;171(5):615-21. doi: 10.1530/EJE-14-0621. PMID: 25305309

Clinical prediction guides

Gullo D, Latina A, Frasca F, Squatrito S, Belfiore A, Vigneri R
Clin Endocrinol (Oxf) 2017 Aug;87(2):207-215. Epub 2017 May 16 doi: 10.1111/cen.13351. PMID: 28398655
Bagattini B, Cosmo CD, Montanelli L, Piaggi P, Ciampi M, Agretti P, Marco GD, Vitti P, Tonacchera M
Eur J Endocrinol 2014 Nov;171(5):615-21. doi: 10.1530/EJE-14-0621. PMID: 25305309

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