Details of Disease

Disease Name

Congenital hypothyroidism

infantile hypothyroidism; congenital hypothyroidism not due to iodine deficiency; fetal iodine deficiency syndrome; congenital goiter; cretinism; foetal iodine deficiency syndrome; congenital goitre; congenital hypothyroidism; congenital iodine deficiency syndrome

Definition

A thyroid hormone deficiency present from birth.

Disease Hierarchy

DISR0H6D: Hypothyroidism

DISL5XVU: Congenital hypothyroidism

Disease Identifiers

MONDO ID

MONDO_0018612

MESH ID

D003409

UMLS CUI

C0010308

MedGen ID

41344

HPO ID

HP:0000851

Orphanet ID

442

SNOMED CT ID

190268003

General Information of Disease (ID: DISL5XVU)

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

This Disease is Treated as An Indication in 2 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Levothyroxine	DMHN027	Approved	Small molecular drug	[1]
Liothyronine	DM6IR3P	Approved	Small molecular drug	[2]
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Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 12 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
CDCA8	TT04YCM	moderate	Biomarker	[3]
EGR1	TTE8LGD	Strong	Biomarker	[4]
EPHA5	TTV9KOD	Strong	Altered Expression	[5]
G6PD	TTKN8W0	Strong	Biomarker	[6]
GH1	TTT3YKH	Strong	Therapeutic	[7]
GHR	TTHJWYD	Strong	Therapeutic	[7]
KSR1	TTHL1TV	Strong	Genetic Variation	[8]
NGFR	TTEDJN4	Strong	Therapeutic	[9]
SLC26A4	TT7X02I	Strong	Biomarker	[10]
SLC5A5	TTW7HI9	Strong	Genetic Variation	[11]
TPO	TT52XDZ	Strong	Genetic Variation	[12]
TRHR	TT4J8MF	Strong	Genetic Variation	[13]
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⏷ Show the Full List of 12 DTT(s)

This Disease Is Related to 3 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC20A1	DTMULXV	Strong	Genetic Variation	[14]
SLC26A7	DTOTME4	Strong	Autosomal recessive	[15]
SLC26A7	DTOTME4	Strong	Genetic Variation	[3]
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This Disease Is Related to 34 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ARPC5	OTFNMMDL	Strong	Biomarker	[16]
ASAH1	OT1DNGXL	Strong	Genetic Variation	[17]
ATP5PD	OTAJDLE2	Strong	Biomarker	[18]
BGLAP	OTK1YLWQ	Strong	Biomarker	[19]
DNAJC17	OTXRONMF	Strong	Biomarker	[20]
DUOX1	OTQ2AEW0	Strong	Biomarker	[21]
DUOXA1	OTNG3HH4	Strong	Biomarker	[21]
DUOXA2	OT7AZBZJ	Strong	Biomarker	[21]
EFNA5	OTOH4DRR	Strong	Altered Expression	[22]
FOXE1	OT5IR5IT	Strong	Genetic Variation	[10]
GLIS3	OTBC960E	Strong	Genetic Variation	[23]
HHEX	OTLIUVYX	Strong	Genetic Variation	[24]
IGSF1	OT3XD6U2	Strong	Biomarker	[25]
INHBB	OT2QLD11	Strong	Biomarker	[26]
IYD	OT8BQWTE	Strong	Biomarker	[10]
NEFH	OTMSCW5I	Strong	Biomarker	[27]
NEFL	OTQESJV4	Strong	Biomarker	[27]
NEFM	OT8VCBNF	Strong	Biomarker	[27]
NKX2-1	OTCMEJTA	Strong	Genetic Variation	[28]
NLGN3	OTKDEC1Q	Strong	Genetic Variation	[29]
NRGN	OTVGE10W	Strong	Altered Expression	[30]
PAX8	OTRPD9MI	Strong	Genetic Variation	[31]
PDCD6	OT2YA5M8	Strong	Altered Expression	[32]
PHPT1	OTFYWNFX	Strong	Genetic Variation	[17]
POU1F1	OTXT8A5C	Strong	Biomarker	[33]
PPARGC1A	OTHCDQ22	Strong	Biomarker	[34]
SERPINA7	OTUYVTSU	Strong	Biomarker	[35]
SLC26A7	OTZ4ZMHV	Strong	Autosomal recessive	[15]
SOX3	OT1CRCOB	Strong	Genetic Variation	[17]
TG	OT3ELHIJ	Strong	Genetic Variation	[36]
TSHB	OTFDI39D	Strong	Biomarker	[35]
TTF1	OT4K90WD	Strong	Genetic Variation	[28]
TTF2	OT5LJOWM	Strong	Biomarker	[37]
NKX2-5	OTS1SAWM	Definitive	Biomarker	[38]
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⏷ Show the Full List of 34 DOT(s)

References

1	Levothyroxine FDA Label
2	Liothyronine FDA Label
3	Molecular Analysis of Congenital Hypothyroidism in Saudi Arabia: SLC26A7 Mutation Is a Novel Defect in Thyroid Dyshormonogenesis.J Clin Endocrinol Metab. 2018 May 1;103(5):1889-1898. doi: 10.1210/jc.2017-02202.
4	Developmentally-induced hypothyroidism alters the expression of Egr-1 and Arc genes and the sensitivity to cannabinoid agonists in the hippocampus. Possible implications for memory and learning.Mol Cell Endocrinol. 2013 Jan 5;365(1):119-28. doi: 10.1016/j.mce.2012.10.004. Epub 2012 Oct 16.
5	c-Fos downregulation positively regulates EphA5 expression in a congenital hypothyroidism rat model.J Mol Histol. 2018 Apr;49(2):147-155. doi: 10.1007/s10735-018-9754-7. Epub 2018 Jan 12.
6	Congenital hypothyroidism alters the oxidative status, enzyme activities and morphological parameters in the hippocampus of developing rats.Mol Cell Endocrinol. 2013 Aug 15;375(1-2):14-26. doi: 10.1016/j.mce.2013.05.001. Epub 2013 May 18.
7	Changes in growth hormone (GH), GH receptor, and GH signal transduction in hippocampus of congenital hypothyroid rats.J Neurosci Res. 2011 Feb;89(2):248-55. doi: 10.1002/jnr.22540. Epub 2010 Dec 8.
8	Sibship with 17-ketosteroid reductase (17-KSR) deficiency and hypothyroidism. Lack of linkage of histocompatibility leucocyte antigen and 17-KSR loci.J Clin Endocrinol Metab. 1983 Jul;57(1):190-6. doi: 10.1210/jcem-57-1-190.
9	Iodine plus n-3 fatty acid supplementation augments rescue of postnatal neuronal abnormalities in iodine-deficient rat cerebellum.Br J Nutr. 2013 Aug;110(4):659-70. doi: 10.1017/S0007114512005569. Epub 2013 Jan 14.
10	Next-generation sequencing analysis of twelve known causative genes in congenital hypothyroidism.Clin Chim Acta. 2017 May;468:76-80. doi: 10.1016/j.cca.2017.02.009. Epub 2017 Feb 16.
11	Novel Sodium/Iodide Symporter Compound Heterozygous Pathogenic Variants Causing Dyshormonogenic Congenital Hypothyroidism.Thyroid. 2019 Jul;29(7):1023-1026. doi: 10.1089/thy.2019.0046. Epub 2019 Jul 2.
12	Thyroid Hypoplasia in Congenital Hypothyroidism Associated with Thyroid Peroxidase Mutations.Thyroid. 2018 Jul;28(7):941-944. doi: 10.1089/thy.2017.0502.
13	A Novel Thyrotropin-Releasing Hormone Receptor Missense Mutation (P81R) in Central Congenital Hypothyroidism.J Clin Endocrinol Metab. 2016 Mar;101(3):847-51. doi: 10.1210/jc.2015-3916. Epub 2016 Jan 6.
14	A new C-terminal located mutation (V272ter) in the PIT-1 gene manifesting with severe congenital hypothyroidism. Possible functionality of the PIT-1 C-terminus.Horm Res. 2001;56(3-4):81-6. doi: 10.1159/000048096.
15	Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
16	Effects of hypothyroidism on expression of CRMP2B and ARPC5 during development of the rat frontal cortex.Int J Biol Sci. 2013;9(2):209-18. doi: 10.7150/ijbs.5646. Epub 2013 Feb 12.
17	A novel mutation causing pseudohypoparathyroidism 1A with congenital hypothyroidism and osteoma cutis.J Clin Res Pediatr Endocrinol. 2009;1(5):244-7. doi: 10.4274/jcrpe.v1i5.244. Epub 2009 Aug 6.
18	[Proteomic changes in cerebral cortex of neonatal rats with experimental congenital hypothyroidism].Zhonghua Er Ke Za Zhi. 2011 Mar;49(3):209-13.
19	Studies on gene expression in calvaria and serum levels of insulin-like growth factor-I and bone Gla protein in the methimazole-induced congenital hypothyroid rat.Endocr J. 1993 Jun;40(3):351-62. doi: 10.1507/endocrj.40.351.
20	DNAJC17 is localized in nuclear speckles and interacts with splicing machinery components.Sci Rep. 2018 May 17;8(1):7794. doi: 10.1038/s41598-018-26093-1.
21	Identification of Two Missense Mutations in DUOX1 (p.R1307Q) and DUOXA1 (p.R56W) That Can Cause Congenital Hypothyroidism Through Impairing H(2)O(2) Generation.Front Endocrinol (Lausanne). 2019 Aug 2;10:526. doi: 10.3389/fendo.2019.00526. eCollection 2019.
22	Abnormal expression of ephrin-A5 affects brain development of congenital hypothyroidism rats.Neuroreport. 2018 Aug 1;29(11):877-882. doi: 10.1097/WNR.0000000000001047.
23	Glis3 as a Critical Regulator of Thyroid Primordium Specification.Thyroid. 2020 Feb;30(2):277-289. doi: 10.1089/thy.2019.0196. Epub 2020 Jan 27.
24	Screening for mutations in transcription factors in a Czech cohort of 170 patients with congenital and early-onset hypothyroidism: identification of a novel PAX8 mutation in dominantly inherited early-onset non-autoimmune hypothyroidism.Eur J Endocrinol. 2007 May;156(5):521-9. doi: 10.1530/EJE-06-0709.
25	Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement. Nat Genet. 2012 Dec;44(12):1375-81. doi: 10.1038/ng.2453. Epub 2012 Nov 11.
26	Developmental expression of testis messenger ribonucleic acids in the rat following propylthiouracil-induced neonatal hypothyroidism.Biol Reprod. 1994 Oct;51(4):706-13. doi: 10.1095/biolreprod51.4.706.
27	Congenital hypothyroidism is associated with intermediate filament misregulation, glutamate transporters down-regulation and MAPK activation in developing rat brain.Neurotoxicology. 2008 Nov;29(6):1092-9. doi: 10.1016/j.neuro.2008.09.004. Epub 2008 Sep 18.
28	Respiratory insufficiency in a newborn with congenital hypothyroidism due to a new mutation of TTF-1/NKX2.1 gene.Pediatr Pulmonol. 2014 Mar;49(3):E42-4. doi: 10.1002/ppul.22788. Epub 2013 Sep 2.
29	Neuroligin trafficking deficiencies arising from mutations in the alpha/beta-hydrolase fold protein family.J Biol Chem. 2010 Sep 10;285(37):28674-82. doi: 10.1074/jbc.M110.139519. Epub 2010 Jul 8.
30	RC3/neurogranin structure and expression in the caprine brain in relation to congenital hypothyroidism.Brain Res Mol Brain Res. 1995 Mar;29(1):119-30. doi: 10.1016/0169-328x(94)00237-9.
31	Systematic alanine scanning of PAX8 paired domain reveals functional importance of the N-subdomain.J Mol Endocrinol. 2019 Apr 1;62(3):129-135. doi: 10.1530/JME-18-0207.
32	microRNA-124-3p inhibits the progression of congenital hypothyroidism via targeting programmed cell death protein 6.Exp Ther Med. 2018 Jun;15(6):5001-5006. doi: 10.3892/etm.2018.6062. Epub 2018 Apr 13.
33	Growth hormone deficiency and combined pituitary hormone deficiency: does the genotype matter?.Clin Endocrinol (Oxf). 2005 Aug;63(2):121-30. doi: 10.1111/j.1365-2265.2005.02289.x.
34	Evidence of a bigenomic regulation of mitochondrial gene expression by thyroid hormone during rat brain development.Biochem Biophys Res Commun. 2010 Jul 2;397(3):548-52. doi: 10.1016/j.bbrc.2010.05.154. Epub 2010 May 31.
35	Molecular spectrum of TSH subunit gene defects in central hypothyroidism in the UK and Ireland.Clin Endocrinol (Oxf). 2017 Mar;86(3):410-418. doi: 10.1111/cen.13149. Epub 2016 Aug 4.
36	The role of thyroglobulin in thyroid hormonogenesis.Nat Rev Endocrinol. 2019 Jun;15(6):323-338. doi: 10.1038/s41574-019-0184-8.
37	Genetics of congenital hypothyroidism. J Med Genet. 2005 May;42(5):379-89. doi: 10.1136/jmg.2004.024158.
38	Transcription factor mutations and congenital hypothyroidism: systematic genetic screening of a population-based cohort of Japanese patients.J Clin Endocrinol Metab. 2010 Apr;95(4):1981-5. doi: 10.1210/jc.2009-2373. Epub 2010 Feb 15.