MCID: HYP374
MIFTS: 39

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 53 28 69
Tsh Resistance 53 71 51
Hypothyroidism Due to Unresponsiveness to Thyrotropin 53 71
Thyrotropin Resistance 53 71
Chng1 53 71
Rtsh 53 71
Hypothyroidism, Congenital, Due to Tsh Resistance 53
Congenital Hypothyroidism Due to Tsh Resistance 71
Hypothyroidism Due to Tsh Receptor Mutations 55
Hypothyroidism, Congenital, Non-Goitrous, 1 71
Thyroid-Stimulating Hormone, Resistance to 53
Hypothyroidism, Congenital, Nongoitrous, 3 69
Thyroid-Stimulating Hormone Resistance 71
Thyroid Hormone Resistance Syndrome 69
Thyroid-Stimulating Hormone ; Rtsh 53
Hypothyroidism, Nonautoimmune 53
Non-Autoimmune Hypothyroidism 71

Characteristics:

Orphanet epidemiological data:

55
hypothyroidism due to tsh receptor mutations
Inheritance: Autosomal dominant,Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

53
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:

31
hypothyroidism, congenital, nongoitrous, 1:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 55  
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 hyperthyroidism, nonautoimmune and hypothyroidism, congenital, nongoitrous, 2, and has symptoms including constipation, dry skin and hypothyroidism. An important gene associated with Hypothyroidism, Congenital, Nongoitrous, 1 is TSHR (Thyroid Stimulating Hormone Receptor), and among its related pathways/superpathways are Aldosterone synthesis and secretion and cAMP signaling pathway. Affiliated tissues include thyroid and skin, and related phenotype is hearing/vestibular/ear.

OMIM : 53 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:

53
Endocrine Features:
euthyroidism
normal sized thyroid gland
no goiter
hypothyroidism in subset of patients
patients with hypothyroidism have hypoplastic thyroid gland

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

Immunology:
absence of anti-thyroid antibodies


Clinical features from OMIM:

275200

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

55 31 (show all 15)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 constipation 55 31 hallmark (90%) Very frequent (99-80%) HP:0002019
2 dry skin 55 31 hallmark (90%) Very frequent (99-80%) HP:0000958
3 hypothyroidism 55 31 hallmark (90%) Very frequent (99-80%) HP:0000821
4 muscular hypotonia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001252
5 sleep disturbance 55 31 hallmark (90%) Very frequent (99-80%) HP:0002360
6 macroglossia 55 31 hallmark (90%) Very frequent (99-80%) HP:0000158
7 umbilical hernia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001537
8 hoarse cry 55 31 hallmark (90%) Very frequent (99-80%) HP:0001615
9 feeding difficulties 55 31 hallmark (90%) Very frequent (99-80%) HP:0011968
10 jaundice 55 31 hallmark (90%) Very frequent (99-80%) HP:0000952
11 large fontanelles 55 31 hallmark (90%) Very frequent (99-80%) HP:0000239
12 abdominal distention 55 31 hallmark (90%) Very frequent (99-80%) HP:0003270
13 thyroid hypoplasia 31 HP:0005990
14 congenital hypothyroidism 31 HP:0000851
15 increased thyroid-stimulating hormone level 31 HP:0002925

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

43
# 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:

# Genetic test Affiliating Genes
1 Hypothyroidism, Congenital, Nongoitrous, 1 28 TSHR

Anatomical Context for Hypothyroidism, Congenital, Nongoitrous, 1

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

38
Thyroid, Skin

Publications for Hypothyroidism, Congenital, Nongoitrous, 1

Articles related to Hypothyroidism, Congenital, Nongoitrous, 1:

# Title Authors Year
1
Nonclassic TSH resistance: TSHR mutation carriers with discrepantly high thyroidal iodine uptake. ( 21677043 )
2011
2
Genetics and phenomics of hypothyroidism due to TSH resistance. ( 20083154 )
2010
3
Intracellular entrapment of wild-type TSH receptor by oligomerization with mutants linked to dominant TSH resistance. ( 16135555 )
2005
4
Thyrotropin receptor gene mutations and TSH resistance: variable expressivity in the heterozygotes. ( 16060907 )
2005
5
Paternal imprinting of Galpha(s) in the human thyroid as the basis of TSH resistance in pseudohypoparathyroidism type 1a. ( 12147228 )
2002

Variations for Hypothyroidism, Congenital, Nongoitrous, 1

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

71 (show all 17)
# 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)
# Gene Variation Type Significance SNP ID Assembly Location
1 TSHR NM_000369.2(TSHR): c.545+2_545+3delTG deletion Likely pathogenic rs786204790 GRCh38 Chromosome 14, 81092610: 81092611
2 TSHR TSHR, 2-BP DEL, 654AC deletion Pathogenic
3 TSHR NM_000369.2(TSHR): c.545+3G> C single nucleotide variant Pathogenic rs786205080 GRCh38 Chromosome 14, 81092611: 81092611
4 TSHR NM_000369.2(TSHR): c.500T> A (p.Ile167Asn) single nucleotide variant Pathogenic rs121908862 GRCh37 Chromosome 14, 81558907: 81558907
5 TSHR NM_000369.2(TSHR): c.484C> G (p.Pro162Ala) single nucleotide variant Pathogenic rs121908863 GRCh37 Chromosome 14, 81558891: 81558891
6 TSHR NM_000369.2(TSHR): c.326G> A (p.Arg109Gln) single nucleotide variant Pathogenic rs121908865 GRCh37 Chromosome 14, 81554306: 81554306
7 TSHR NM_000369.2(TSHR): c.970C> T (p.Gln324Ter) single nucleotide variant Pathogenic rs121908867 GRCh37 Chromosome 14, 81609372: 81609372
8 TSHR NM_000369.2(TSHR): c.1228G> A (p.Asp410Asn) single nucleotide variant Pathogenic rs121908868 GRCh37 Chromosome 14, 81609630: 81609630
9 TSHR NM_000369.2(TSHR): c.122G> C (p.Cys41Ser) single nucleotide variant Pathogenic rs121908869 GRCh37 Chromosome 14, 81422146: 81422146
10 TSHR NM_000369.2(TSHR): c.1575C> A (p.Phe525Leu) single nucleotide variant Pathogenic rs121908870 GRCh37 Chromosome 14, 81609977: 81609977
11 TSHR NM_000369.2(TSHR): c.1170T> G (p.Cys390Trp) single nucleotide variant Pathogenic rs121908871 GRCh37 Chromosome 14, 81609572: 81609572
12 TSHR TSHR, 18-BP DEL, 4-BP INS indel Pathogenic
13 TSHR NM_000369.2(TSHR): c.1430C> T (p.Thr477Ile) single nucleotide variant Pathogenic rs121908881 GRCh37 Chromosome 14, 81609832: 81609832
14 TSHR NM_000369.2(TSHR): c.928C> T (p.Arg310Cys) single nucleotide variant Pathogenic rs121908882 GRCh37 Chromosome 14, 81609330: 81609330
15 TSHR NM_000369.2(TSHR): c.1798T> C (p.Cys600Arg) single nucleotide variant Pathogenic rs121908884 GRCh37 Chromosome 14, 81610200: 81610200
16 TSHR NM_000369.2(TSHR): c.1400T> C (p.Leu467Pro) single nucleotide variant Pathogenic rs121908885 GRCh37 Chromosome 14, 81609802: 81609802
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:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.99 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:

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

Sources for Hypothyroidism, Congenital, Nongoitrous, 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
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47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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