MCID: HYP374
MIFTS: 36

Hypothyroidism, Congenital, Nongoitrous, 1

Categories: Genetic diseases, Endocrine diseases, Rare diseases

Aliases & Classifications for Hypothyroidism, Congenital, Nongoitrous, 1

MalaCards integrated aliases for Hypothyroidism, Congenital, Nongoitrous, 1:

Name: Hypothyroidism, Congenital, Nongoitrous, 1 54 29 69
Tsh Resistance 71 52
Chng1 24 71
Hypothyroidism Due to Unresponsiveness to Thyrotropin 71
Congenital Hypothyroidism Due to Tsh Resistance 71
Hypothyroidism Due to Tsh Receptor Mutations 56
Hypothyroidism, Congenital, Non-Goitrous, 1 71
Hypothyroidism, Congenital, Nongoitrous, 3 69
Congenital Hypothyroidism, Nongoitrous 1 24
Thyroid-Stimulating Hormone Resistance 71
Thyroid Hormone Resistance Syndrome 69
Non-Autoimmune Hypothyroidism 71
Thyrotropin Resistance 71
Rtsh 71

Characteristics:

Orphanet epidemiological data:

56
hypothyroidism due to tsh receptor mutations
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

54
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
most patients are asymptomatic and are detected by newborn screening
variable severity ranging from asymptomatic euthyroid to severe hypothyroidism


HPO:

32
hypothyroidism, congenital, nongoitrous, 1:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 56  
Rare endocrine diseases


Summaries for Hypothyroidism, Congenital, Nongoitrous, 1

UniProtKB/Swiss-Prot : 71 Hypothyroidism, congenital, non-goitrous, 1: A non-autoimmune condition characterized by resistance to thyroid- stimulating hormone (TSH) leading to increased levels of plasma TSH and low levels of thyroid hormone. It presents variable severity depending on the completeness of the defect. Most patients are euthyroid and asymptomatic, with a normal sized thyroid gland. Only a subset of patients develop hypothyroidism and present a hypoplastic thyroid gland.

MalaCards based summary : Hypothyroidism, Congenital, Nongoitrous, 1, also known as tsh resistance, is related to pseudohypoparathyroidism, type ib and hypothyroidism, congenital, due to thyroid dysgenesis or hypoplasia, and has symptoms including macroglossia, umbilical hernia and jaundice. An important gene associated with Hypothyroidism, Congenital, Nongoitrous, 1 is TSHR (Thyroid Stimulating Hormone Receptor), and among its related pathways/superpathways are Insulin secretion and cAMP signaling pathway. Affiliated tissues include thyroid and skin, and related phenotype is hearing/vestibular/ear.

OMIM : 54
Resistance to thyroid-stimulating hormone (TSH; see 188540), a hallmark of congenital nongoitrous hypothyroidism, causes increased levels of plasma TSH and low levels of thyroid hormone. Only a subset of patients develop frank hypothyroidism; the remainder are euthyroid and asymptomatic (so-called compensated hypothyroidism) and are usually detected by neonatal screening programs (Paschke and Ludgate, 1997). (275200)

Related Diseases for Hypothyroidism, Congenital, Nongoitrous, 1

Graphical network of the top 20 diseases related to Hypothyroidism, Congenital, Nongoitrous, 1:



Diseases related to Hypothyroidism, Congenital, Nongoitrous, 1

Symptoms & Phenotypes for Hypothyroidism, Congenital, Nongoitrous, 1

Symptoms via clinical synopsis from OMIM:

54

Laboratory- Abnormalities:
increased serum thyroid-stimulating hormone (tsh)
normal or mildly decreased serum levels of free thyroid hormones

Immunology:
absence of anti-thyroid antibodies

Endocrine Features:
euthyroidism
normal sized thyroid gland
no goiter
hypothyroidism in subset of patients
patients with hypothyroidism have hypoplastic thyroid gland


Clinical features from OMIM:

275200

Human phenotypes related to Hypothyroidism, Congenital, Nongoitrous, 1:

56 32 (show all 15)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macroglossia 56 32 hallmark (90%) Very frequent (99-80%) HP:0000158
2 umbilical hernia 56 32 hallmark (90%) Very frequent (99-80%) HP:0001537
3 jaundice 56 32 hallmark (90%) Very frequent (99-80%) HP:0000952
4 large fontanelles 56 32 hallmark (90%) Very frequent (99-80%) HP:0000239
5 constipation 56 32 hallmark (90%) Very frequent (99-80%) HP:0002019
6 hoarse cry 56 32 hallmark (90%) Very frequent (99-80%) HP:0001615
7 dry skin 56 32 hallmark (90%) Very frequent (99-80%) HP:0000958
8 feeding difficulties 56 32 hallmark (90%) Very frequent (99-80%) HP:0011968
9 hypothyroidism 56 32 hallmark (90%) Very frequent (99-80%) HP:0000821
10 muscular hypotonia 56 32 hallmark (90%) Very frequent (99-80%) HP:0001252
11 abdominal distention 56 32 hallmark (90%) Very frequent (99-80%) HP:0003270
12 sleep disturbance 56 32 hallmark (90%) Very frequent (99-80%) HP:0002360
13 congenital hypothyroidism 32 HP:0000851
14 thyroid hypoplasia 32 HP:0005990
15 increased thyroid-stimulating hormone level 32 HP:0002925

MGI Mouse Phenotypes related to Hypothyroidism, Congenital, Nongoitrous, 1:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 hearing/vestibular/ear MP:0005377 8.62 GNAS TSHR

Drugs & Therapeutics for Hypothyroidism, Congenital, Nongoitrous, 1

Search Clinical Trials , NIH Clinical Center for Hypothyroidism, Congenital, Nongoitrous, 1

Genetic Tests for Hypothyroidism, Congenital, Nongoitrous, 1

Genetic tests related to Hypothyroidism, Congenital, Nongoitrous, 1:

id Genetic test Affiliating Genes
1 Hypothyroidism, Congenital, Nongoitrous, 1 29
2 Congenital Hypothyroidism, Nongoitrous 1 24 TSHR

Anatomical Context for Hypothyroidism, Congenital, Nongoitrous, 1

MalaCards organs/tissues related to Hypothyroidism, Congenital, Nongoitrous, 1:

39
Thyroid, Skin

Publications for Hypothyroidism, Congenital, Nongoitrous, 1

Variations for Hypothyroidism, Congenital, Nongoitrous, 1

UniProtKB/Swiss-Prot genetic disease variations for Hypothyroidism, Congenital, Nongoitrous, 1:

71 (show all 17)
id Symbol AA change Variation ID SNP ID
1 TSHR p.Cys41Ser VAR_011519
2 TSHR p.Arg109Gln VAR_011520
3 TSHR p.Pro162Ala VAR_011521 rs121908863
4 TSHR p.Ile167Asn VAR_011522
5 TSHR p.Arg310Cys VAR_011524
6 TSHR p.Cys390Trp VAR_011525
7 TSHR p.Asp410Asn VAR_011526
8 TSHR p.Arg450His VAR_011528
9 TSHR p.Gly498Ser VAR_011533
10 TSHR p.Phe525Leu VAR_011537
11 TSHR p.Ala553Thr VAR_011538
12 TSHR p.Leu467Pro VAR_017295
13 TSHR p.Thr477Ile VAR_017296
14 TSHR p.Cys600Arg VAR_017297
15 TSHR p.Leu252Pro VAR_021495
16 TSHR p.Asn432Asp VAR_075585
17 TSHR p.Pro449Leu VAR_075586

ClinVar genetic disease variations for Hypothyroidism, Congenital, Nongoitrous, 1:

6 (show all 18)
id Gene Variation Type Significance SNP ID Assembly Location
1 TSHR NM_000369.2(TSHR): c.500T> A (p.Ile167Asn) single nucleotide variant Pathogenic rs121908862 GRCh37 Chromosome 14, 81558907: 81558907
2 TSHR NM_000369.2(TSHR): c.484C> G (p.Pro162Ala) single nucleotide variant Pathogenic rs121908863 GRCh37 Chromosome 14, 81558891: 81558891
3 TSHR NM_000369.2(TSHR): c.326G> A (p.Arg109Gln) single nucleotide variant Pathogenic rs121908865 GRCh37 Chromosome 14, 81554306: 81554306
4 TSHR NM_000369.2(TSHR): c.970C> T (p.Gln324Ter) single nucleotide variant Pathogenic rs121908867 GRCh37 Chromosome 14, 81609372: 81609372
5 TSHR NM_000369.2(TSHR): c.1228G> A (p.Asp410Asn) single nucleotide variant Pathogenic rs121908868 GRCh37 Chromosome 14, 81609630: 81609630
6 TSHR NM_000369.2(TSHR): c.122G> C (p.Cys41Ser) single nucleotide variant Pathogenic rs121908869 GRCh37 Chromosome 14, 81422146: 81422146
7 TSHR NM_000369.2(TSHR): c.1575C> A (p.Phe525Leu) single nucleotide variant Pathogenic rs121908870 GRCh37 Chromosome 14, 81609977: 81609977
8 TSHR NM_000369.2(TSHR): c.1170T> G (p.Cys390Trp) single nucleotide variant Pathogenic rs121908871 GRCh37 Chromosome 14, 81609572: 81609572
9 TSHR TSHR, 18-BP DEL, 4-BP INS indel Pathogenic
10 TSHR NM_000369.2(TSHR): c.1430C> T (p.Thr477Ile) single nucleotide variant Pathogenic rs121908881 GRCh37 Chromosome 14, 81609832: 81609832
11 TSHR NM_000369.2(TSHR): c.928C> T (p.Arg310Cys) single nucleotide variant Pathogenic rs121908882 GRCh37 Chromosome 14, 81609330: 81609330
12 TSHR NM_000369.2(TSHR): c.1798T> C (p.Cys600Arg) single nucleotide variant Pathogenic rs121908884 GRCh37 Chromosome 14, 81610200: 81610200
13 TSHR NM_000369.2(TSHR): c.1400T> C (p.Leu467Pro) single nucleotide variant Pathogenic rs121908885 GRCh37 Chromosome 14, 81609802: 81609802
14 TSHR TSHR, 2-BP DEL, 654AC deletion Pathogenic
15 TSHR NM_000369.2(TSHR): c.545+3G> C single nucleotide variant Pathogenic rs786205080 GRCh38 Chromosome 14, 81092611: 81092611
16 TSHR NM_000369.2(TSHR): c.545+2_545+3delTG deletion Likely pathogenic rs786204790 GRCh37 Chromosome 14, 81558954: 81558955
17 TSHR NM_000369.2(TSHR): c.1349G> A (p.Arg450His) single nucleotide variant Pathogenic rs189261858 GRCh37 Chromosome 14, 81609751: 81609751
18 TSHR NM_000369.2(TSHR): c.202C> T (p.Pro68Ser) single nucleotide variant Likely pathogenic rs142063461 GRCh37 Chromosome 14, 81528523: 81528523

Expression for Hypothyroidism, Congenital, Nongoitrous, 1

Search GEO for disease gene expression data for Hypothyroidism, Congenital, Nongoitrous, 1.

Pathways for Hypothyroidism, Congenital, Nongoitrous, 1

Pathways related to Hypothyroidism, Congenital, Nongoitrous, 1 according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1
Show member pathways
11.72 GNAS TSHR
2
Show member pathways
11.56 GNAS TSHR
3 11.32 GNAS TSHR
4 10.79 GNAS TSHR
5 10.36 GNAS TSHR

GO Terms for Hypothyroidism, Congenital, Nongoitrous, 1

Biological processes related to Hypothyroidism, Congenital, Nongoitrous, 1 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 positive regulation of cAMP biosynthetic process GO:0030819 9.16 GNAS TSHR
2 adenylate cyclase-activating G-protein coupled receptor signaling pathway GO:0007189 8.96 GNAS TSHR
3 activation of adenylate cyclase activity GO:0007190 8.62 GNAS TSHR

Sources for Hypothyroidism, Congenital, Nongoitrous, 1

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10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
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30 HGMD
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65 SNOMED-CT via HPO
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67 TGDB
68 Tocris
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70 UMLS via Orphanet
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