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CH
MCID: CNG006
MIFTS: 64

Congenital Hypothyroidism (CH)

Categories: Endocrine diseases, Fetal diseases, Immune diseases, Mental diseases, Metabolic diseases, Neuronal diseases, Rare diseases
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Aliases & Classifications for Congenital Hypothyroidism

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MalaCards integrated aliases for Congenital Hypothyroidism:

Name: Congenital Hypothyroidism 11 19 42 58 75 28 53 5 43 14 71 33
Cretinism 42 75
Congenital Iodine-Deficiency Hypothyroidism Nos 33
Congenital Iodine-Deficiency Syndrome 33
Fetal Iodine Deficiency Syndrome 33
Neonatal Hypothyroidism 19
Myxedema, Congenital 71
Congenital Myxedema 42
Endemic Cretinism 71
Cht 42
Ch 42

Characteristics:


Inheritance:

Autosomal recessive 58

Prevelance:

1-5/10000 (Europe, Europe, France, Italy, Cyprus, Latvia, China, Germany, Denmark, Poland, Estonia, Lebanon, Turkey, Australia, Taiwan, Province of China, Mexico, Bosnia and Herzegovina, Bahrain, New Zealand, Thailand, Specific population, Czech Republic, Ireland) 6-9/10000 (Greece, United Arab Emirates, Bangladesh, Pakistan, Brazil) >1/1000 (Iran, Islamic Republic of) 58

Age Of Onset:

Antenatal,Neonatal 58

Classifications:

MalaCards categories:
Global: Rare diseases Metabolic diseases Fetal diseases
Anatomical: Endocrine diseases Neuronal diseases Immune diseases Mental diseases
See all MalaCards categories (disease lists)
ICD10: 31
ICD11: 33
Orphanet: 58  
Rare endocrine diseases


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Summaries for Congenital Hypothyroidism

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MedlinePlus Genetics: 42 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.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.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 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.

MalaCards based summary: Congenital Hypothyroidism, also known as cretinism, is related to diabetes mellitus, neonatal, with congenital hypothyroidism and hypothyroidism, congenital, nongoitrous, 2. An important gene associated with Congenital Hypothyroidism is TG (Thyroglobulin), and among its related pathways/superpathways are Regulation of expression of SLITs and ROBOs and Thyroid hormones production and peripheral downstream signaling effects. The drugs Pharmaceutical Solutions and Iodine have been mentioned in the context of this disorder. Affiliated tissues include thyroid, pituitary and brain, and related phenotypes are sleep disturbance and constipation

GARD: 19 Congenital hypothyroidism is a condition that affects infants from birth and results from a partial or complete loss of thyroid function (hypothyroidism). The thyroid gland makes hormones that play an important role in regulating growth, brain development, and metabolism in the body. Congenital hypothyroidism occurs when the thyroid gland fails to develop or function properly. Most cases of Congenital hypothyroidism occur in people with no history of the disorder in their family. Some cases are due to an underlying genetic change. Rarely, Congenital hypothyroidism can be a symptom included in a larger genetic disorder called a syndrome.

Orphanet: 58 Congenital hypothyroidism (CH) is defined as a thyroid hormone deficiency present from birth.

Disease Ontology: 11 A hypothyroidism that is present at birth.

Wikipedia 75 Congenital hypothyroidism: Congenital hypothyroidism (CH) is thyroid hormone deficiency present at birth. If untreated for several... more...

Cretinism: Congenital iodine deficiency syndrome is a medical condition present at birth marked by impaired... more...
Sources

Related Diseases for Congenital Hypothyroidism

About this section

Diseases in the Hypothyroidism family:

Congenital Hypothyroidism Central Congenital Hypothyroidism
Hypothyroidism Due to Iodide Transport Defect Rare Adult Hypothyroidism
Transient Congenital Hypothyroidism Rare Hypothyroidism
Primary Congenital Hypothyroidism Hypothyroidism Due to Deficient Transcription Factors Involved in Pituitary Development or Function
Congenital Hypothyroidism Due to Maternal Intake of Antithyroid Drugs Transient Congenital Hypothyroidism Due to Maternal Factor
Transient Congenital Hypothyroidism Due to Neonatal Factor Congenital Hypothyroidism Due to Transplacental Passage of Tsh-Binding Inhibitory Antibodies
Congenital Hypothyroidism Due to Developmental Anomaly

Diseases related to Congenital Hypothyroidism via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 605)
# Related Disease Score Top Affiliating Genes
1 diabetes mellitus, neonatal, with congenital hypothyroidism 33.3 SLC5A5 IYD GLIS3 FOXE1
2 hypothyroidism, congenital, nongoitrous, 2 33.3 TSHR TG PAX8-AS1 PAX8 NKX2-1 FOXE1
3 hypothyroidism, congenital, nongoitrous, 1 33.0 TSHR TSHB TG PAX8 IYD GNAS
4 hypothyroidism, central, with testicular enlargement 33.0 TSHB POU1F1
5 thyroid dyshormonogenesis 2a 32.9 TSHR TPO TG PAX8 NKX2-1
6 thyroid dyshormonogenesis 1 32.9 SLC5A5 PAX8
7 pendred syndrome 32.7 TPO TG SLC5A5 SLC26A7 PAX8 IYD
8 hypothyroidism, congenital, nongoitrous, 4 32.7 TSHB TPO TG POU1F1
9 familial thyroid dyshormonogenesis 32.6 TPO TG SLC5A5 IYD DUOXA2 DUOX2
10 hypothyroidism 32.6 TSHR TSHB TPO TG SLC5A5 SLC26A7
11 athyreosis 32.5 TSHR PAX8 NKX2-5 NKX2-1 FOXE1
12 hypothyroidism, thyroidal or athyroidal, with spiky hair and cleft palate 32.5 TSHR PAX8 NKX2-1 IYD FOXE1 DUOXA2
13 thyroid ectopia 32.4 PAX8 NKX2-5
14 goiter 31.8 TSHR TPO TG SLC5A5 PAX8 NKX2-1
15 graves disease 1 31.7 TSHR TPO TG SLC5A5
16 hyperthyroidism 31.5 TSHR TPO TG GNAS
17 thyroiditis 31.3 TSHR TSHB TPO TG
18 graves' disease 31.1 TSHR TPO TG PAX8 GNAS
19 hashimoto thyroiditis 31.1 TSHR TPO TG
20 nontoxic goiter 31.0 TSHR TPO TG
21 myxedema 30.8 TSHR TSHB TPO TG
22 nodular goiter 30.8 TSHR TPO TG SLC5A5
23 thyroid hormone resistance, generalized, autosomal dominant 30.7 TSHR TSHB TG
24 dyshormonogenic goiter 30.7 TG SLC5A5 SLC26A7 IYD DUOXA2 DUOX2
25 multinodular goiter 30.7 TSHR TPO TG SLC5A5 PAX8 NKX2-1
26 thyroid malformation 30.6 PAX8 NKX2-5 NKX2-1 IYD FOXE1
27 endemic goiter 30.6 TSHR TSHB TPO TG SLC5A5 PAX8
28 pituitary gland disease 30.5 TSHB POU1F1 GNAS
29 thyroid hormone resistance, selective pituitary 30.5 TSHB TG
30 hyperthyroxinemia 30.5 TSHR TPO
31 neonatal thyrotoxicosis 30.4 TSHR TG
32 thyroid cancer, nonmedullary, 2 30.4 TSHR TG PAX8
33 differentiated thyroid carcinoma 30.4 PAX8 NKX2-1 FOXE1
34 papillary carcinoma 30.4 TSHR TPO TG PAX8 NKX2-1 GNAS
35 adenoma 30.4 TSHR TSHB TG POU1F1 GNAS
36 thyroid gland cancer 30.4 TSHR TPO TG SLC5A5 PAX8 NKX2-1
37 goiter, multinodular 1, with or without sertoli-leydig cell tumors 30.3 TPO TG
38 choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction 11.6
39 permanent congenital hypothyroidism 11.6
40 central congenital hypothyroidism 11.6
41 primary congenital hypothyroidism 11.5
42 congenital hypothyroidism due to developmental anomaly 11.4
43 idiopathic congenital hypothyroidism 11.4
44 primary congenital hypothyroidism without thyroid developmental anomaly 11.4
45 congenital hypothyroidism due to maternal intake of antithyroid drugs 11.4
46 congenital hypothyroidism due to transplacental passage of tsh-binding inhibitory antibodies 11.4
47 transient congenital hypothyroidism 11.3
48 genetic transient congenital hypothyroidism 11.3
49 hypothyroidism, congenital, nongoitrous, 7 11.2
50 hypothyroidism, congenital, nongoitrous, 3 11.2

Comorbidity relations with Congenital Hypothyroidism via Phenotypic Disease Network (PDN):


Hypothyroidism

Graphical network of the top 20 diseases related to Congenital Hypothyroidism:



Diseases related to Congenital Hypothyroidism
Sources

Symptoms & Phenotypes for Congenital Hypothyroidism

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Human phenotypes related to Congenital Hypothyroidism:

58 30 (show top 50) (show all 52)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 sleep disturbance 58 30 Hallmark (90%) Very frequent (99-80%)
 HP:0002360
2 constipation 58 30 Hallmark (90%) Very frequent (99-80%)
 HP:0002019
3 hypothyroidism 58 30 Hallmark (90%) Very frequent (99-80%)
 HP:0000821
4 hypotonia 58 30 Hallmark (90%) Very frequent (99-80%)
 HP:0001252
5 macroglossia 58 30 Hallmark (90%) Very frequent (99-80%)
 HP:0000158
6 umbilical hernia 58 30 Hallmark (90%) Very frequent (99-80%)
 HP:0001537
7 feeding difficulties in infancy 58 30 Hallmark (90%) Very frequent (99-80%)
 HP:0008872
8 prolonged neonatal jaundice 58 30 Hallmark (90%) Very frequent (99-80%)
 HP:0006579
9 abdominal distention 58 30 Hallmark (90%) Very frequent (99-80%)
 HP:0003270
10 large posterior fontanelle 58 30 Hallmark (90%) Very frequent (99-80%)
 HP:0004491
11 thyroid dysgenesis 58 30 Hallmark (90%) Very frequent (99-80%)
 HP:0008188
12 depression 58 30 Frequent (33%) Frequent (79-30%)
 HP:0000716
13 hypothermia 58 30 Frequent (33%) Frequent (79-30%)
 HP:0002045
14 coarse facial features 58 30 Frequent (33%) Frequent (79-30%)
 HP:0000280
15 global developmental delay 58 30 Frequent (33%) Frequent (79-30%)
 HP:0001263
16 short stature 58 30 Frequent (33%) Frequent (79-30%)
 HP:0004322
17 intellectual disability, severe 58 30 Frequent (33%) Frequent (79-30%)
 HP:0010864
18 sinusitis 58 30 Frequent (33%) Frequent (79-30%)
 HP:0000246
19 anxiety 58 30 Frequent (33%) Frequent (79-30%)
 HP:0000739
20 palpebral edema 58 30 Frequent (33%) Frequent (79-30%)
 HP:0100540
21 reduced tendon reflexes 58 30 Frequent (33%) Frequent (79-30%)
 HP:0001315
22 depressed nasal ridge 58 30 Frequent (33%) Frequent (79-30%)
 HP:0000457
23 anosmia 58 30 Frequent (33%) Frequent (79-30%)
 HP:0000458
24 hypogonadism 58 30 Frequent (33%) Frequent (79-30%)
 HP:0000135
25 angiokeratoma corporis diffusum 58 30 Frequent (33%) Frequent (79-30%)
 HP:0001071
26 hoarse cry 58 30 Frequent (33%) Frequent (79-30%)
 HP:0001615
27 abnormal hair morphology 30 Frequent (33%) HP:0001595
28 hypotension 58 30 Occasional (7.5%) Occasional (29-5%)
 HP:0002615
29 hypertension 58 30 Occasional (7.5%) Occasional (29-5%)
 HP:0000822
30 hearing impairment 58 30 Occasional (7.5%) Occasional (29-5%)
 HP:0000365
31 cataract 58 30 Occasional (7.5%) Occasional (29-5%)
 HP:0000518
32 optic atrophy 58 30 Occasional (7.5%) Occasional (29-5%)
 HP:0000648
33 nephrolithiasis 58 30 Occasional (7.5%) Occasional (29-5%)
 HP:0000787
34 anterior hypopituitarism 58 30 Occasional (7.5%) Occasional (29-5%)
 HP:0000830
35 arrhythmia 58 30 Occasional (7.5%) Occasional (29-5%)
 HP:0011675
36 abnormality of vision 58 30 Occasional (7.5%) Occasional (29-5%)
 HP:0000504
37 tracheoesophageal fistula 58 30 Occasional (7.5%) Occasional (29-5%)
 HP:0002575
38 paresthesia 58 30 Occasional (7.5%) Occasional (29-5%)
 HP:0003401
39 intestinal obstruction 58 30 Occasional (7.5%) Occasional (29-5%)
 HP:0005214
40 goiter 58 30 Occasional (7.5%) Occasional (29-5%)
 HP:0000853
41 oral cleft 58 30 Occasional (7.5%) Occasional (29-5%)
 HP:0000202
42 abnormal pericardium morphology 58 30 Occasional (7.5%) Occasional (29-5%)
 HP:0001697
43 abnormal epiphysis morphology 30 Occasional (7.5%) HP:0005930
44 intellectual disability 58 Frequent (79-30%)
45 abnormality of the eye 58 Occasional (29-5%)
46 abnormality of epiphysis morphology 58 Occasional (29-5%)
47 abnormality of the face 58 Very frequent (99-80%)
48 abnormal eyelid morphology 58 Frequent (79-30%)
49 large fontanelles 58 Very frequent (99-80%)
50 abnormality of the hair 58 Frequent (79-30%)

MGI Mouse Phenotypes related to Congenital Hypothyroidism:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 10.24 DUOX2 DUOXA2 FOXE1 GLIS3 GNAS NKX2-1
2 growth/size/body region MP:0005378 10.07 DUOX2 DUOXA2 FOXE1 GLIS3 GNAS NKX2-1
3 hearing/vestibular/ear MP:0005377 9.97 DUOX2 DUOXA2 GNAS PAX8 POU1F1 SLC5A5
4 endocrine/exocrine gland MP:0005379 9.97 DUOX2 FOXE1 GLIS3 GNAS NKX2-1 NKX2-5
5 limbs/digits/tail MP:0005371 9.95 DUOX2 DUOXA2 GNAS PAX8 TG TPO
6 craniofacial MP:0005382 9.5 DUOXA2 FOXE1 GNAS NKX2-5 PAX8 POU1F1
7 skeleton MP:0005390 9.36 DUOX1 DUOX2 DUOXA2 GNAS NKX2-1 PAX8
Sources

Drugs & Therapeutics for Congenital Hypothyroidism

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Drugs for Congenital Hypothyroidism (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Pharmaceutical Solutions Phase 4
2
Iodine Approved, Investigational 7553-56-2 807
3
Cadexomer iodine Experimental 94820-09-4
4 Sodium Pertechnetate Tc 99m

Interventional clinical trials:

(show all 14)
# Name Status NCT ID Phase Drugs
1 Evaluation of Long-term Benefit-risk Profile of Levothyroxine Treatment in Children With Congenital Hypothyroidism: Influence of Initial Levothyroxine Dose on Neurodevelopmental, Growth, Cardiovascular and Skeletal Outcomes Completed NCT05371262 Phase 4 Levothyroxin
2 A Randomized Comparative Study Between Liquid (Tirosint®-SOL) and Tablet Formulations of Levothyroxine in Neonates and Infants With Congenital Hypothyroidism Recruiting NCT05228184 Phase 4 Tirosint®-SOL;Levothyroxine Sodium
3 Iodine Status in Pregnant Women and Their Newborns: is Congenital Hypothyroidism Related to Iodine Deficiency in Pregnancy? Unknown status NCT00505479
4 Congenital Hypothyroidism Due to Thyroglobulin Mutations in an Inbred Brazilian Family: A Novel Compound Heterozygous Constellation and Intronic Mutation Related to Fetal Goiter. Completed NCT00493103
5 Phenotype and Genotype Analysis in Congenital Hypothyroidism Due to Thyroid Dysgenesis. The Use of Genetic Analysis in the Early Care of Children With Thyroid Dysgenesis Completed NCT01916018
6 Targeted Levothyroxine Dosing in Infants With Congenital Hypothyroidism Completed NCT02374593 Levothyroxine
7 A Phase I Study of 99m Tc Pertechnetate Produced in High Energy Cyclotron (CYCLOTEC) in Patients With Thyroid Scan Indication Completed NCT02307175
8 Diagnosis and Follow-up of Patients With Subclinical Hypothyroidism Completed NCT00497575
9 Generic vs. Name-Brand Levothyroxine: Assessment of Bioequivalence Using TSH as a Marker in Children With Permanent Hypothyroidism Completed NCT00403390 Brand Name Levothyroxine (Synthroid);Generic formulation of Levothyroxine
10 Clinical Evaluation of the xMAP® NeoPlex4™ Assay for Detection of T4, TSH, 17-OHP and IRT Using the NeoPlex System Completed NCT01488721
11 A Study to Measure the Effect of Switching the Salt Supply From Non-iodized to Iodized on Cognitive Development in Ethiopia Completed NCT01349634
12 Congenital Hypothyroidism in Children With Eutopic Gland or Thyroid Hemiagenesis: Predictive Factors for Transient vs Permanent Hypothyroidism. Recruiting NCT04712760
13 Final Height in Patients With Congenital Hypothyroidism Diagnosed by Neonatal Screening Not yet recruiting NCT04734457 Levothyroxin
14 The Prevalence of Hearing Loss Among Children With Congenital Hypothyroidism Withdrawn NCT01223638

Search NIH Clinical Center for Congenital Hypothyroidism

Cochrane evidence based reviews: congenital hypothyroidism

Sources

Genetic Tests for Congenital Hypothyroidism

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Genetic tests related to Congenital Hypothyroidism:

# Genetic test Affiliating Genes
1 Congenital Hypothyroidism 28
Sources

Anatomical Context for Congenital Hypothyroidism

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Organs/tissues related to Congenital Hypothyroidism:

MalaCards : Thyroid, Pituitary, Brain, Tongue, Lung, Bone, Skin
Sources

Publications for Congenital Hypothyroidism

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Articles related to Congenital Hypothyroidism:

(show top 50) (show all 4989)
# Title Authors PMID Year
1
Identification and functional studies of two new dual-oxidase 2 (DUOX2) mutations in a child with congenital hypothyroidism and a eutopic normal-size thyroid gland. 53 62 5
19789206 2009
2
TSHR mutations as a cause of congenital hypothyroidism in Japan: a population-based genetic epidemiology study. 53 62 5
19158199 2009
3
Congenital hypothyroidism with goitre caused by new mutations in the thyroglobulin gene. 53 62 5
17532758 2007
4
Congenital hypothyroidism caused by new mutations in the thyroid oxidase 2 (THOX2) gene. 53 62 5
17121535 2006
5
Screening for Pax8 mutations in patients with congenital hypothyroidism in South-West Germany. 53 62 5
16763387 2006
6
A novel mutation in the sodium/iodide symporter gene in the largest family with iodide transport defect. 53 62 5
10487695 1999
7
Next-generation sequencing of NKX2.1, FOXE1, PAX8, NKX2.5, and TSHR in 100 Chinese patients with congenital hypothyroidism and athyreosis. 62 5
28455095 2017
8
A frequent oligogenic involvement in congenital hypothyroidism. 62 5
28444304 2017
9
Next-generation sequencing analysis of TSHR in 384 Chinese subclinical congenital hypothyroidism (CH) and CH patients. 62 5
27637299 2016
10
DUOX2 Mutations Are Frequently Associated With Congenital Hypothyroidism in the Korean Population. 62 5
26709262 2016
11
PAX8 pathogenic variants in Chinese patients with congenital hypothyroidism. 62 5
26362610 2015
12
Identification of a novel pax8 gene sequence variant in four members of the same family: from congenital hypothyroidism with thyroid hypoplasia to mild subclinical hypothyroidism. 62 5
25146893 2014
13
R450H TSH receptor mutation in congenital hypothyroidism in Taiwanese children. 62 5
22405933 2012
14
Molecular screening of the TSH receptor (TSHR) and thyroid peroxidase (TPO) genes in Korean patients with nonsyndromic congenital hypothyroidism. 62 5
21707688 2011
15
Nonclassic TSH resistance: TSHR mutation carriers with discrepantly high thyroidal iodine uptake. 62 5
21677043 2011
16
The R450H mutation and D727E polymorphism of the thyrotropin receptor gene in a Chinese child with congenital hypothyroidism. 62 5
21714469 2010
17
Determining the frequency of pathogenic germline variants from exome sequencing in patients with castrate-resistant prostate cancer. 5
27084275 2016
18
Frequency and clinical implication of the R450H mutation in the thyrotropin receptor gene in the Japanese population detected by Smart Amplification Process 2. 5
24895636 2014
19
Genetic analysis in children with transient thyroid dysfunction or subclinical hypothyroidism detected on neonatal screening. 5
23926367 2009
20
Longitudinal evaluation of patients with a homozygous R450H mutation of the TSH receptor gene. 5
19506388 2009
21
Clinical significance of heterozygous carriers associated with compensated hypothyroidism in R450H, a common inactivating mutation of the thyrotropin receptor gene in Japanese. 5
17526952 2006
22
Clinical case seminar: metastatic follicular thyroid carcinoma arising from congenital goiter as a result of a novel splice donor site mutation in the thyroglobulin gene. 5
16403815 2006
23
Subclinical hypothyroidism caused by a mutation of the thyrotropin receptor gene. 5
15693879 2005
24
Novel inactivating missense mutations in the thyrotropin receptor gene in Japanese children with resistance to thyrotropin. 5
11442002 2001
25
A premature stopcodon in thyroglobulin messenger RNA results in familial goiter and moderate hypothyroidism. 5
10404833 1999
26
A nonsense mutation causes human hereditary congenital goiter with preferential production of a 171-nucleotide-deleted thyroglobulin ribonucleic acid messenger. 5
8325944 1993
27
Genetics and phenomics of hypothyroidism and goiter due to NIS mutations. 53 62
20153805 2010
28
Compound heterozygosity for a novel hemizygous missense mutation and a partial deletion affecting the catalytic core of the H2O2-generating enzyme DUOX2 associated with transient congenital hypothyroidism. 53 62
20187165 2010
29
Biallelic p.R2223H mutation in the thyroglobulin gene causes thyroglobulin retention and severe hypothyroidism with subsequent development of thyroid carcinoma. 53 62
20089614 2010
30
Congenital hypothyroidism and late-onset goiter: identification and characterization of a novel mutation in the sodium/iodide symporter of the proband and family members. 53 62
19916865 2009
31
Six new mutations of the thyroglobulin gene discovered in taiwanese children presenting with thyroid dyshormonogenesis. 53 62
19837936 2009
32
Thyrotropin-stimulating hormone receptor gene analysis in pediatric patients with non-autoimmune subclinical hypothyroidism. 53 62
19820021 2009
33
The p.A2215D thyroglobulin gene mutation leads to deficient synthesis and secretion of the mutated protein and congenital hypothyroidism with wide phenotype variation. 53 62
19509106 2009
34
Two novel mutations in the human thyroid peroxidase (TPO) gene: genetics and clinical findings in four children. 53 62
19243353 2009
35
Five new TTF1/NKX2.1 mutations in brain-lung-thyroid syndrome: rescue by PAX8 synergism in one case. 53 62
19336474 2009
36
Heterodimerization controls localization of Duox-DuoxA NADPH oxidases in airway cells. 53 62
19339556 2009
37
Mutations in TAZ/WWTR1, a co-activator of NKX2.1 and PAX8 are not a frequent cause of thyroid dysgenesis. 53 62
19542741 2009
38
Functional studies of new TSH receptor (TSHr) mutations identified in patients affected by hypothyroidism or isolated hyperthyrotrophinaemia. 53 62
18727713 2009
39
[Updating neonatal neurometabolic screening]. 53 62
19240000 2009
40
Transient congenital hypothyroidism caused by biallelic mutations of the dual oxidase 2 gene in Japanese patients detected by a neonatal screening program. 53 62
18765513 2008
41
New mutation type in pseudohypoparathyroidism type Ia. 53 62
18394017 2008
42
Congenital hypothyroidism caused by a novel homozygous mutation in the thyroid peroxidase gene. 53 62
19189706 2008
43
Coverage of the Victorian newborn screening programme in 2003: a retrospective population study. 53 62
18557804 2008
44
Phenotypic variation among four family members with congenital hypothyroidism caused by two distinct thyroglobulin gene mutations. 53 62
18631008 2008
45
A novel homozygous missense mutation of the dual oxidase 2 (DUOX2) gene in an adult patient with large goiter. 53 62
18426362 2008
46
Identification and characterization of four PAX8 rare sequence variants (p.T225M, p.L233L, p.G336S and p.A439A) in patients with congenital hypothyroidism and dysgenetic thyroid glands. 53 62
17980011 2008
47
Thyrotropin receptor and thyroid transcription factor-1 genes variant in Chinese children with congenital hypothyroidism. 53 62
18379122 2008
48
Biallelic inactivation of the dual oxidase maturation factor 2 (DUOXA2) gene as a novel cause of congenital hypothyroidism. 53 62
18042646 2008
49
Pseudodominant inheritance of goitrous congenital hypothyroidism caused by TPO mutations: molecular and in silico studies. 53 62
18029453 2008
50
Thyroglobulin and human thyroid cancer. 53 62
18060877 2008
Sources

Variations for Congenital Hypothyroidism

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ClinVar genetic disease variations for Congenital Hypothyroidism:

5 (show top 50) (show all 53)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TUBB1 NM_030773.4(TUBB1):c.479C>T (p.Pro160Leu) SNV Pathogenic
 586964 rs759117911 GRCh37: 20:57598961-57598961
GRCh38: 20:59023906-59023906
2 TUBB1 NM_030773.4(TUBB1):c.318C>G (p.Tyr106Ter) SNV Pathogenic
 586965 rs560702757 GRCh37: 20:57598800-57598800
GRCh38: 20:59023745-59023745
3 TG NM_003235.5(TG):c.638+1G>A SNV Pathogenic
 12706 rs1587178555 GRCh37: 8:133885467-133885467
GRCh38: 8:132873222-132873222
4 TG NM_003235.5(TG):c.6701C>A (p.Ala2234Asp) SNV Pathogenic
 988639 rs370991693 GRCh37: 8:134030161-134030161
GRCh38: 8:133017916-133017916
5 TG NM_003235.5(TG):c.5182T>C (p.Cys1728Arg) SNV Pathogenic
 988643 rs376200169 GRCh37: 8:133953736-133953736
GRCh38: 8:132941491-132941491
6 TPO NM_001206744.2(TPO):c.866T>C (p.Phe289Ser) SNV Pathogenic
 988647 rs1670028028 GRCh37: 2:1480904-1480904
GRCh38: 2:1477132-1477132
7 PAX8-AS1, PAX8 NM_003466.4(PAX8):c.101T>A (p.Ile34Asn) SNV Pathogenic
 988648 rs1691361089 GRCh37: 2:114004421-114004421
GRCh38: 2:113246844-113246844
8 PAX8-AS1, PAX8 NM_003466.4(PAX8):c.397C>T (p.Arg133Trp) SNV Pathogenic
 988649 rs1690970101 GRCh37: 2:114000348-114000348
GRCh38: 2:113242771-113242771
9 SLC5A5 NM_000453.3(SLC5A5):c.1183G>A (p.Gly395Arg) SNV Pathogenic
 7670 rs121909180 GRCh37: 19:17992969-17992969
GRCh38: 19:17882160-17882160
10 TG NM_003235.5(TG):c.4588C>T (p.Arg1530Ter) SNV Pathogenic
 12691 rs121912646 GRCh37: 8:133935642-133935642
GRCh38: 8:132923397-132923397
11 TG NM_003235.5(TG):c.649dup (p.Ala217fs) DUP Pathogenic
 988641 rs1814692109 GRCh37: 8:133894117-133894118
GRCh38: 8:132881872-132881873
12 PAX8-AS1, PAX8 NM_003466.4(PAX8):c.658C>T (p.Arg220Ter) SNV Pathogenic
 988652 rs1690853952 GRCh37: 2:113999247-113999247
GRCh38: 2:113241670-113241670
13 DUOX2 NM_001363711.2(DUOX2):c.598G>A (p.Gly200Arg) SNV Pathogenic
 888352 rs2467827 GRCh37: 15:45403699-45403699
GRCh38: 15:45111501-45111501
14 TG NM_003235.5(TG):c.886C>T (p.Arg296Ter) SNV Pathogenic
 12695 rs121912648 GRCh37: 8:133894854-133894854
GRCh38: 8:132882609-132882609
15 DUOX2 NM_001363711.2(DUOX2):c.3155G>A (p.Cys1052Tyr) SNV Pathogenic
 631732 rs76343591 GRCh37: 15:45392277-45392277
GRCh38: 15:45100079-45100079
16 DUOXA2 NM_207581.4(DUOXA2):c.205+2T>C SNV Pathogenic
 265105 rs201506037 GRCh37: 15:45408056-45408056
GRCh38: 15:45115858-45115858
17 DUOXA2 NM_207581.4(DUOXA2):c.463C>G (p.Leu155Val) SNV Pathogenic
 372358 rs201808443 GRCh37: 15:45408836-45408836
GRCh38: 15:45116638-45116638
18 TSHR NM_000369.5(TSHR):c.1349G>A (p.Arg450His) SNV Pathogenic
 225505 rs189261858 GRCh37: 14:81609751-81609751
GRCh38: 14:81143407-81143407
19 TUBB1 NM_030773.4(TUBB1):c.35del (p.Cys12fs) DEL Pathogenic
 586966 rs773248042 GRCh37: 20:57594612-57594612
GRCh38: 20:59019557-59019557
20 DUOX2 NM_001363711.2(DUOX2):c.2895_2898del (p.Phe966fs) DEL Pathogenic
 189229 rs530719719 GRCh37: 15:45393426-45393429
GRCh38: 15:45101228-45101231
21 DUOX2 NM_001363711.2(DUOX2):c.602dup (p.Gln202fs) DUP Likely Pathogenic
 279800 rs567500345 GRCh37: 15:45403694-45403695
GRCh38: 15:45111496-45111497
22 TG NM_003235.5(TG):c.5299_5301del (p.Asp1767del) DEL Likely Pathogenic
 712030 rs112749206 GRCh37: 8:133961086-133961088
GRCh38: 8:132948841-132948843
23 DUOX2 NM_001363711.2(DUOX2):c.3416-1G>A SNV Likely Pathogenic
 1120118 GRCh37: 15:45391681-45391681
GRCh38: 15:45099483-45099483
24 TPO NM_001206744.2(TPO):c.1768+1_1768+9dup DUP Likely Pathogenic
 988651 rs1385139268 GRCh37: 2:1491756-1491757
GRCh38: 2:1487984-1487985
25 TG NM_003235.5(TG):c.2234dup (p.Leu746fs) DUP Likely Pathogenic
 988644 rs1815680018 GRCh37: 8:133900285-133900286
GRCh38: 8:132888040-132888041
26 TG NM_003235.5(TG):c.3452del (p.Val1151fs) DEL Likely Pathogenic
 988645 rs766130576 GRCh37: 8:133913616-133913616
GRCh38: 8:132901371-132901371
27 TG NM_003235.5(TG):c.2134dup (p.Ala712fs) DUP Likely Pathogenic
 988640 rs1815591671 GRCh37: 8:133899749-133899750
GRCh38: 8:132887504-132887505
28 SLC26A7 NM_052832.4(SLC26A7):c.1498C>T (p.Gln500Ter) SNV Likely Pathogenic
 828176 rs774517670 GRCh37: 8:92378817-92378817
GRCh38: 8:91366589-91366589
29 TPO NM_001206744.2(TPO):c.1558C>T (p.His520Tyr) SNV Likely Pathogenic
 374178 rs1057518950 GRCh37: 2:1488587-1488587
GRCh38: 2:1484815-1484815
30 DUOX2 NM_001363711.2(DUOX2):c.3416-7C>G SNV Uncertain Significance
 316152 rs886051192 GRCh37: 15:45391687-45391687
GRCh38: 15:45099489-45099489
31 IYD NM_203395.3(IYD):c.*1382CT[3] MICROSAT Uncertain Significance
 355712 rs886061172 GRCh37: 6:150720755-150720756
GRCh38: 6:150399619-150399620
32 TPO NM_001206744.2(TPO):c.1566T>A (p.Ala522=) SNV Uncertain Significance
 331319 rs17091745 GRCh37: 2:1488595-1488595
GRCh38: 2:1484823-1484823
33 DUOX2 NM_001363711.2(DUOX2):c.944-10C>T SNV Uncertain Significance
 316179 rs756654827 GRCh37: 15:45402732-45402732
GRCh38: 15:45110534-45110534
34 IYD NM_203395.3(IYD):c.*3405del DEL Uncertain Significance
 355753 rs770486449 GRCh37: 6:150722775-150722775
GRCh38: 6:150401639-150401639
35 TPO NM_001206744.2(TPO):c.*63dup DUP Uncertain Significance
 331643 rs749486726 GRCh37: 2:1546305-1546306
GRCh38: 2:1542533-1542534
36 TSHR NM_000369.5(TSHR):c.*1742G>T SNV Uncertain Significance
 314723 rs886050861 GRCh37: 14:81612439-81612439
GRCh38: 14:81146095-81146095
37 PAX8 NM_003466.4(PAX8):c.*2503_*2504dup DUP Uncertain Significance
 330852 rs751887254 GRCh37: 2:113973605-113973606
GRCh38: 2:113216028-113216029
38 IYD NM_203395.3(IYD):c.*5785dup DUP Uncertain Significance
 355782 rs761967547 GRCh37: 6:150725154-150725155
GRCh38: 6:150404018-150404019
39 IYD NM_203395.3(IYD):c.*461del DEL Uncertain Significance
 355691 rs61597872 GRCh37: 6:150719823-150719823
GRCh38: 6:150398687-150398687
40 IYD NM_203395.3(IYD):c.*6375del DEL Uncertain Significance
 355791 rs886061184 GRCh37: 6:150725748-150725748
GRCh38: 6:150404612-150404612
41 IYD NM_203395.3(IYD):c.*672_*673delinsTG INDEL Uncertain Significance
 355700 rs374913437 GRCh37: 6:150720045-150720046
GRCh38: 6:150398909-150398910
42 TSHR NM_000369.5(TSHR):c.*137del DEL Uncertain Significance
 314702 rs886050856 GRCh37: 14:81610831-81610831
GRCh38: 14:81144487-81144487
43 DUOX2 NM_001363711.2(DUOX2):c.314G>A (p.Gly105Glu) SNV Uncertain Significance
 316192 rs556820857 GRCh37: 15:45404763-45404763
GRCh38: 15:45112565-45112565
44 IYD NM_203395.2(IYD):c.-104T>A SNV Uncertain Significance
 355671 rs886061163 GRCh37: 6:150690064-150690064
GRCh38: 6:150368928-150368928
45 TSHR NM_000369.5(TSHR):c.*1154dup DUP Likely Benign
 314715 rs3214569 GRCh37: 14:81611850-81611851
GRCh38: 14:81145506-81145507
46 TPO NM_001206744.2(TPO):c.2007-9_2007-7del DEL Likely Benign
 331361 rs28991288 GRCh37: 2:1499750-1499752
GRCh38: 2:1495978-1495980
47 IYD NM_203395.3(IYD):c.*460_*461del DEL Likely Benign
 355692 rs61597872 GRCh37: 6:150719823-150719824
GRCh38: 6:150398687-150398688
48 TG NM_003235.5(TG):c.7859G>A (p.Gly2620Asp) SNV Likely Benign
 988642 rs978923522 GRCh37: 8:134128957-134128957
GRCh38: 8:133116713-133116713
49 SLC26A4 NM_000441.2(SLC26A4):c.199A>C (p.Thr67Pro) SNV Benign
 988646 rs1174526823 GRCh37: 7:107303775-107303775
GRCh38: 7:107663330-107663330
50 IYD NM_203395.3(IYD):c.*4676_*4677insGGGGGTGATTCACCT INSERT Benign
 355766 rs11268976 GRCh37: 6:150724047-150724048
GRCh38: 6:150402911-150402912

Copy number variations for Congenital Hypothyroidism from CNVD:

6
# CNVD ID Chromosome Start End Type Gene Symbol CNVD Disease
1 225757 7 50314923 50440292 Copy number Congenital hypothyroidism
Sources

Expression for Congenital Hypothyroidism

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Search GEO for disease gene expression data for Congenital Hypothyroidism.
Sources

Pathways for Congenital Hypothyroidism

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Pathways directly related to Congenital Hypothyroidism:

# Pathway Source
1 Defective SLC5A5 causes thyroid dyshormonogenesis 1 (TDH1) Reactome 66

Pathways related to Congenital Hypothyroidism according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Regulation of expression of SLITs and ROBOs 66
Show member pathways
 12.68 TSHB TPO SLC5A5 IYD DUOX2 DUOX1
2
Thyroid hormones production and peripheral downstream signaling effects 74
11.55 TSHR TSHB SLC5A5 IYD DUOXA2 DUOX2
3
Thyroid stimulating hormone (TSH) signaling pathway 74
11.2 TSHR TSHB GNAS
4
Metabolism of amine-derived hormones 66
Show member pathways
 10.94 TSHB TPO SLC5A5 IYD DUOX2 DUOX1
5
Hormone ligand-binding receptors 66
10.45 TSHR TSHB
6
Thyroxine (thyroid hormone) production 74
10.4 TSHR TPO TG SLC5A5 DUOX2 DUOX1
Sources

GO Terms for Congenital Hypothyroidism

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Cellular components related to Congenital Hypothyroidism according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cell leading edge GO:0031252 9.1 DUOXA2 DUOX2 DUOX1

Biological processes related to Congenital Hypothyroidism according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 hydrogen peroxide catabolic process GO:0042744 9.88 TPO DUOX2 DUOX1
2 positive regulation of cell motility GO:2000147 9.85 DUOXA2 DUOX2 DUOX1
3 hydrogen peroxide biosynthetic process GO:0050665 9.8 DUOX2 DUOX1
4 cellular response to gonadotropin stimulus GO:0071371 9.78 SLC5A5 PAX8
5 iodide transport GO:0015705 9.76 TG SLC5A5
6 hormone biosynthetic process GO:0042446 9.76 TPO TG DUOX2 DUOX1
7 cuticle development GO:0042335 9.73 DUOX2 DUOX1
8 thyroid hormone generation GO:0006590 9.73 TPO TG SLC5A5 FOXE1 DUOX2 DUOX1
9 thyroid-stimulating hormone signaling pathway GO:0038194 9.62 TSHR PAX8
10 thyroid hormone metabolic process GO:0042403 9.56 DUOX2 IYD TG
11 thyroid gland development GO:0030878 9.4 TUBB1 TG PAX8 NKX2-5 NKX2-1 FOXE1

Molecular functions related to Congenital Hypothyroidism according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 sequence-specific DNA binding GO:0043565 9.98 PAX8 NKX2-5 NKX2-1 GLIS3 FOXE1
2 peroxidase activity GO:0004601 9.8 TPO DUOX2 DUOX1
3 superoxide-generating NAD(P)H oxidase activity GO:0016175 9.71 DUOX2 DUOX1
4 NAD(P)H oxidase H2O2-forming activity GO:0016174 9.67 DUOX2 DUOX1
5 NADPH oxidase H202-forming activity GO:0106294 9.56 DUOX2 DUOX1
6 NADH oxidase H202-forming activity GO:0106293 9.26 DUOX2 DUOX1
7 oxidoreductase activity, acting on NAD(P)H, oxygen as acceptor GO:0050664 9.16 DUOX2 DUOX1
8 thyroid-stimulating hormone receptor activity GO:0004996 8.92 TSHR PAX8
Sources

Sources for Congenital Hypothyroidism

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2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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