MCID: HYP273
MIFTS: 44

Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or Hypoplasia

Categories: Genetic diseases, Rare diseases, Endocrine diseases, Immune diseases

Aliases & Classifications for Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or...

MalaCards integrated aliases for Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or Hypoplasia:

Name: Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or Hypoplasia 54 13
Thyroid Dysgenesis 50 71 29 42 69
Thyroid Hypoplasia 50 56 29 69
Thyroid Hemiagenesis 56 69
Thyroid Agenesis 50 29
Chng2 24 71
Congenital Hypothyroidism Due to Thyroid Dysgenesis 71
Hypothyroidism, Congenital, Non-Goitrous, 2 71
Hypothyroidism, Congenital, Nongoitrous, 1 69
Hypothyroidism, Congenital, Nongoitrous, 3 69
Congenital Hypothyroidism, Nongoitrous 2 24
Thyroid-Stimulating Hormone Resistance 71
Thyroid Hormone Resistance Syndrome 69
Athyreotic Hypothyroidism 71
Thyrotropin Resistance 71
Thyroid, Ectopic 50
Thyroid Ectopic 52
Rtsh 71

Characteristics:

Orphanet epidemiological data:

56
thyroid hypoplasia
Prevalence: 1-9/100000 (Worldwide);

OMIM:

54
Inheritance:
autosomal dominant

Miscellaneous:
maternal autoantibodies
female to male ratio 2:1
rare in blacks


Classifications:

Orphanet: 56  
Rare endocrine diseases


Summaries for Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or...

NIH Rare Diseases : 50 the following summary is from orphanet, a european reference portal for information on rare diseases and orphan drugs.orpha number: 95720disease definitionthyroid hypoplasia is a form of thyroid dysgenesis (see this term) characterized by incomplete development of the thyroid gland that results in primary congenital hypothyroidism (see this term), a permanent thyroid deficiency that is present from birth.epidemiologyprevalence is estimated at around 1/28,000. thyroid hypoplasia and athyreosis (see this term) combined account for one-third of cases of thyroid dysgenesis.clinical descriptionclinical manifestations of thyroid hypoplasia are often subtle or not present at birth, 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 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 thyroid hypoplasia results in severe intellectual deficit and short stature.etiologyfamilial cases of thyroid hypoplasia are caused by mutations in the foxe1, nkx2-1, nkx2-5 or pax8 genes (9q22, 14q13, 5q34 and 2q12-q14). mutations that result in partial inactivation of the tshr gene (14q31) can present with thyroid hypoplasia.diagnostic methodsimaging studies are required to confirm the diagnosis.genetic counselingthyroid hypoplasia is generally thought to be sporadic. however, recent evidence points to the possibility of a genetic component. around 2% of cases have been shown to be familial.visit the orphanet disease page for more resources. last updated: 8/5/2010

MalaCards based summary : Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or Hypoplasia, also known as thyroid dysgenesis, is related to bamforth syndrome and bamforth-lazarus syndrome, and has symptoms including short stature, macroglossia and umbilical hernia. An important gene associated with Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or Hypoplasia is PAX8 (Paired Box 8), and among its related pathways/superpathways are Insulin secretion and Human Thyroid Stimulating Hormone (TSH) signaling pathway. Affiliated tissues include thyroid, tongue and skin, and related phenotypes are endocrine/exocrine gland and homeostasis/metabolism

UniProtKB/Swiss-Prot : 71 Hypothyroidism, congenital, non-goitrous, 2: A disease characterized by thyroid dysgenesis, the most frequent cause of congenital hypothyroidism, accounting for 85% of case. The thyroid gland can be completely absent (athyreosis), ectopically located and/or severely hypoplastic. Ectopic thyroid gland is the most frequent malformation, with thyroid tissue being found most often at the base of the tongue.

OMIM : 54
In 80 to 85% of cases, congenital hypothyroidism is associated with, and presumably is a consequence of, thyroid dysgenesis (Macchia et al., 1998). In these cases, the thyroid gland can be absent (agenesis), ectopically located, and/or severely reduced in size (hypoplasia). When thyroid hormone therapy is not initiated within the first 2 months of life, congenital hypothyroidism can cause severe neurologic, mental, and motor damage (cretinism). (218700)

Related Diseases for Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or...

Diseases in the Hypothyroidism family:

Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or Hypoplasia Congenital Hypothyroidism
Central Congenital Hypothyroidism Hypothyroidism Due to Iodide Transport Defect
Congenital Hypothyroidism, Duoxa2-Related Congenital Hypothyroidism, Duox2-Related
Congenital Hypothyroidism, Iyd-Related Congenital Hypothyroidism, Tpo-Related
Hypothyroidism Due to Deficient Transcription Factors Involved in Pituitary Development or Function Congenital Hypothyroidism Due to Maternal Intake of Antithyroid Drugs
Congenital Hypothyroidism Due to Transplacental Passage of Maternal Tsh-Binding Inhibitory Antibodies

Diseases related to Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or Hypoplasia via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 55)
id Related Disease Score Top Affiliating Genes
1 bamforth syndrome 11.0
2 bamforth-lazarus syndrome 10.8
3 hypothyroidism, congenital, nongoitrous, 1 10.8
4 thyroiditis 10.4
5 potter's syndrome 10.4 PAX8 TSHR
6 hypothyroidism 10.3
7 congenital hypothyroidism 10.2
8 urethral villous adenoma 10.2 NKX2-1 PAX8
9 pulmonary neuroendocrine tumor 10.2 PAX8 TG
10 chronic polyneuropathy 10.2 TG TSHR
11 conjunctival deposit 10.1 TG TSHR
12 parietal lobe neoplasm 10.0 FOXE1 TG
13 iridocyclitis 10.0 TG TSHR
14 c5 deficiency 10.0 FOXE1 TG
15 mature teratoma 10.0 NKX2-1 TG
16 combined cellular and humoral immune defects with granulomas 9.9 TG TSHR
17 nephrogenic systemic fibrosis 9.9 PAX8 TG TSHR
18 fallopian tube leiomyoma 9.9 NKX2-1 TG
19 lymphoma 9.9 TG TSHR
20 deafness, autosomal recessive 4, with enlarged vestibular aqueduct 9.8 PAX8 SLC26A4 TG
21 chronic neutrophilic leukemia 9.8 LGALS3 NKX2-1
22 tibia absent polydactyly arachnoid cyst 9.8 NKX2-1 PAX8 TG
23 kidney disease 9.7 NKX2-1 TG TSHR
24 parachordoma 9.7 NKX2-1 TG TSHR
25 background diabetic retinopathy 9.7 SERPINA7 TG TSHR
26 amelogenesis imperfecta, hypomaturation type, iia6 9.7 SERPINA7 TG TSHR
27 cerebral lipidosis 9.7 SERPINA7 TG TSHR
28 endemic goiter 9.7 SERPINA7 TG TSHR
29 echinostomiasis 9.7 SERPINA7 SLC26A4 TG
30 lung occult large cell carcinoma 9.7 SERPINA7 TG TSHR
31 cd3zeta deficiency 9.7 SERPINA7 TG TSHR
32 cloacogenic carcinoma 9.7 SERPINA7 TG TSHR
33 skin meningioma 9.7 SERPINA7 TG TSHR
34 pulsating exophthalmos 9.6 SERPINA7 TG TSHR
35 medullary thyroid carcinoma, familial 9.6 NKX2-1 TG
36 graves' disease 9.6
37 rubella 9.6
38 neonatal hypothyroidism 9.6
39 lacrimal system cancer 9.6 TG TSHR
40 benign shuddering attacks 9.4 LGALS3 PAX8 TG
41 nodular prostate 9.4 LGALS3 TG TSHR
42 demyelinating polyneuropathy 9.3 LGALS3 NKX2-1 TG
43 diabetes mellitus, insulin-dependent, 12 9.0 LGALS3 SLC26A4 TG TSHR
44 meningovascular neurosyphilis 9.0 NKX2-1 PAX8 SLC26A4 TG TSHR
45 primary bacterial infectious disease 9.0 FOXE1 NKX2-1 PAX8 TG TSHR
46 non-distal trisomy 10q 8.9 FOXE1 NKX2-1 PAX8 TG TSHR
47 bladder diffuse clear cell adenocarcinoma 8.6 LGALS3 NKX2-1 PAX8 TG TSHR
48 gastrointestinal system cancer 8.6 LGALS3 NKX2-1 PAX8 TG TSHR
49 chorea, hereditary benign 8.6 LGALS3 NKX2-1 PAX8 TG TSHR
50 frontotemporal dementia and/or amyotrophic lateral sclerosis 4 8.6 LGALS3 NKX2-1 PAX8 TG TSHR

Graphical network of the top 20 diseases related to Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or Hypoplasia:



Diseases related to Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or Hypoplasia

Symptoms & Phenotypes for Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or...

Symptoms via clinical synopsis from OMIM:

54

Neurologic- Central Nervous System:
hypotonia
lethargy
hypothermia

Abdomen- External Features:
umbilical hernia
abdominal distention

Abdomen- Gastroin testinal:
constipation

Cardiovascular- Heart:
bradycardia

Head And Neck- Head:
large posterior fontanel

Abdomen- Biliary Tract:
prolonged physiologic hyperbilirubinemia

Skin Nails & Hair- Skin:
dry
puffy

Head And Neck- Mouth:
macroglossia

Growth- Other:
poor feeding
delayed growth

Voice:
hoarse cry

Endocrine Features:
goiter
ectopic thyroid
hypoplastic thyroid
thyroid agenesis

Respiratory- Nasopharynx:
noisy breathing
nasal stuffiness

Skeletal:
delayed skeletal maturation

Laboratory- Abnormalities:
low t4
high tsh


Clinical features from OMIM:

218700

Human phenotypes related to Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or Hypoplasia:

56 32 (show all 31)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 short stature 56 32 frequent (33%) Frequent (79-30%) HP:0004322
2 macroglossia 56 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0000158
3 umbilical hernia 56 32 hallmark (90%) Very frequent (99-80%) HP:0001537
4 intellectual disability, severe 56 32 frequent (33%) Frequent (79-30%) HP:0010864
5 jaundice 56 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0000952
6 coarse facial features 56 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0000280
7 large fontanelles 56 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0000239
8 fatigue 56 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0012378
9 global developmental delay 56 32 hallmark (90%) Very frequent (99-80%),Frequent (79-30%) HP:0001263
10 constipation 56 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0002019
11 hypothyroidism 56 32 hallmark (90%) Very frequent (99-80%) HP:0000821
12 muscular hypotonia 56 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001252
13 abdominal distention 56 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0003270
14 thyroid agenesis 56 32 hallmark (90%) Very frequent (99-80%) HP:0008191
15 growth delay 56 32 hallmark (90%) Very frequent (99-80%),Very frequent (99-80%) HP:0001510
16 thyroid hypoplasia 56 32 hallmark (90%) Very frequent (99-80%) HP:0005990
17 hypersomnia 56 32 hallmark (90%) Very frequent (99-80%) HP:0100786
18 lethargy 32 HP:0001254
19 hoarse cry 32 HP:0001615
20 dry skin 32 HP:0000958
21 bradycardia 32 HP:0001662
22 hyperbilirubinemia 32 HP:0002904
23 goiter 32 HP:0000853
24 feeding difficulties in infancy 32 HP:0008872
25 hypothermia 32 HP:0002045
26 delayed skeletal maturation 32 HP:0002750
27 ectopic thyroid 32 HP:0100028
28 congenital hypothyroidism 32 HP:0000851
29 large posterior fontanelle 32 HP:0004491
30 abnormality of the face 56 Very frequent (99-80%),Very frequent (99-80%)
31 increased thyroid-stimulating hormone level 32 HP:0002925

MGI Mouse Phenotypes related to Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or Hypoplasia:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 endocrine/exocrine gland MP:0005379 9.8 FOXE1 NKX2-1 PAX8 SLC26A4 TG TSHR
2 homeostasis/metabolism MP:0005376 9.8 FOXE1 LGALS3 NKX2-1 PAX8 SLC26A4 TG
3 nervous system MP:0003631 9.63 SLC26A4 TG TSHR LGALS3 NKX2-1 PAX8
4 reproductive system MP:0005389 9.35 LGALS3 NKX2-1 PAX8 SLC26A4 TSHR
5 skeleton MP:0005390 9.02 LGALS3 NKX2-1 PAX8 SLC26A4 TSHR

Drugs & Therapeutics for Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or...

Search Clinical Trials , NIH Clinical Center for Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or Hypoplasia

Cochrane evidence based reviews: thyroid dysgenesis

Genetic Tests for Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or...

Genetic tests related to Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or Hypoplasia:

id Genetic test Affiliating Genes
1 Thyroid Agenesis 29
2 Thyroid Dysgenesis 29
3 Thyroid Hypoplasia 29
4 Congenital Hypothyroidism, Nongoitrous 2 24 PAX8

Anatomical Context for Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or...

MalaCards organs/tissues related to Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or Hypoplasia:

39
Thyroid, Tongue, Skin

Publications for Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or...

Variations for Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or...

UniProtKB/Swiss-Prot genetic disease variations for Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or Hypoplasia:

71
id Symbol AA change Variation ID SNP ID
1 PAX8 p.Arg31His VAR_012769 rs104893657
2 PAX8 p.Gln40Pro VAR_012770 rs104893656
3 PAX8 p.Cys57Tyr VAR_012771 rs104893659
4 PAX8 p.Leu62Arg VAR_012772 rs104893658

ClinVar genetic disease variations for Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or Hypoplasia:

6 (show all 17)
id Gene Variation Type Significance SNP ID Assembly Location
1 PAX8 NM_013953.3(PAX8): c.322C> T (p.Arg108Ter) single nucleotide variant Pathogenic rs104893655 GRCh37 Chromosome 2, 114002071: 114002071
2 PAX8 NM_013953.3(PAX8): c.92G> A (p.Arg31His) single nucleotide variant Pathogenic rs104893657 GRCh37 Chromosome 2, 114004430: 114004430
3 PAX8 NM_013953.3(PAX8): c.185T> G (p.Leu62Arg) single nucleotide variant Pathogenic rs104893658 GRCh37 Chromosome 2, 114004337: 114004337
4 PAX8 NM_013953.3(PAX8): c.170G> A (p.Cys57Tyr) single nucleotide variant Pathogenic rs104893659 GRCh37 Chromosome 2, 114004352: 114004352
5 PAX8 NM_013953.3(PAX8): c.160A> G (p.Ser54Gly) single nucleotide variant Pathogenic rs104893660 GRCh37 Chromosome 2, 114004362: 114004362
6 PAX8 NM_013953.3(PAX8): c.119A> C (p.Gln40Pro) single nucleotide variant Pathogenic rs104893656 GRCh37 Chromosome 2, 114004403: 114004403
7 PAX8 NM_013953.3(PAX8): c.143C> T (p.Ser48Phe) single nucleotide variant Pathogenic rs121917719 GRCh37 Chromosome 2, 114004379: 114004379
8 PSMA1 GRCh37/hg19 11p15.2(chr11: 14504463-14909461)x1 copy number loss Likely pathogenic GRCh37 Chromosome 11, 14504463: 14909461
9 PSMA1 GRCh37/hg19 11p15.2(chr11: 14657389-14918308)x1 copy number loss Likely pathogenic GRCh37 Chromosome 11, 14657389: 14918308
10 PSMA3 GRCh37/hg19 14q23.1(chr14: 58737402-58884615)x1 copy number loss Likely pathogenic GRCh37 Chromosome 14, 58737402: 58884615
11 PSMA3 GRCh37/hg19 14q23.1(chr14: 58737402-58891576)x1 copy number loss Likely pathogenic GRCh37 Chromosome 14, 58737402: 58891576
12 VPS13C GRCh37/hg19 15q22.2(chr15: 62128861-62340126)x1 copy number loss Likely pathogenic GRCh37 Chromosome 15, 62128861: 62340126
13 VPS13C GRCh37/hg19 15q22.2(chr15: 62155282-62332980)x1 copy number loss Likely pathogenic GRCh37 Chromosome 15, 62155282: 62332980
14 PSMD3 GRCh37/hg19 17q21.1(chr17: 38146929-38153473)x1 copy number loss Likely pathogenic GRCh37 Chromosome 17, 38146929: 38153473
15 LINC01121 GRCh37/hg19 2p21(chr2: 45453858-45455897)x3 copy number gain Likely pathogenic GRCh37 Chromosome 2, 45453858: 45455897
16 LINC01121 GRCh37/hg19 2p21(chr2: 45454554-45457111)x3 copy number gain Likely pathogenic GRCh37 Chromosome 2, 45454554: 45457111
17 PAX8 NM_003466.3(PAX8): c.160A> T (p.Ser54Cys) single nucleotide variant Likely pathogenic rs104893660 GRCh38 Chromosome 2, 113246785: 113246785

Expression for Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or...

Search GEO for disease gene expression data for Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or Hypoplasia.

Pathways for Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or...

Pathways related to Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or Hypoplasia according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1
Show member pathways
11.42 PAX8 SERPINA7 SLC26A4 TG TSHR
2 10.99 PAX8 TSHR
3 9.73 TG TSHR

GO Terms for Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or...

Biological processes related to Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or Hypoplasia according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 iodide transport GO:0015705 9.16 SLC26A4 TG
2 thyroid-stimulating hormone signaling pathway GO:0038194 8.96 PAX8 TSHR
3 thyroid gland development GO:0030878 8.92 FOXE1 NKX2-1 PAX8 TG

Molecular functions related to Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or Hypoplasia according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 thyroid-stimulating hormone receptor activity GO:0004996 8.62 PAX8 TSHR

Sources for Hypothyroidism, Congenital, Due to Thyroid Dysgenesis or...

3 CDC
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9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
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33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
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42 MeSH
43 MESH via Orphanet
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55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
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70 UMLS via Orphanet
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