CHTE
MCID: HYP856
MIFTS: 37

Hypothyroidism, Central, with Testicular Enlargement (CHTE)

Categories: Endocrine diseases, Genetic diseases, Rare diseases, Reproductive diseases

Aliases & Classifications for Hypothyroidism, Central, with Testicular Enlargement

MalaCards integrated aliases for Hypothyroidism, Central, with Testicular Enlargement:

Name: Hypothyroidism, Central, with Testicular Enlargement 57
Hypothyroidism, Central, and Testicular Enlargement 57 73 29 13 6
Igsf1 Deficiency Syndrome 12 58 15
Chte 57 12 73
X-Linked Central Congenital Hypothyroidism with Late-Onset Testicular Enlargement 12 58
X-Linked Central Congenital Hypothyroidism with Late-Onset Macroorchidism 12 58
Central Hypothyroidism and Testicular Enlargement 12 36
Hypothyroidism, Central, Testicular Enlargement 39

Characteristics:

Orphanet epidemiological data:

58
x-linked central congenital hypothyroidism with late-onset testicular enlargement
Inheritance: X-linked recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 05-Mar-2021)
Inheritance:
x-linked recessive

Miscellaneous:
intrafamilial variability in severity of hypothyroidism
some female carriers exhibit central hypothyroidism
some female carriers exhibit low prolactin levels


HPO:

31
hypothyroidism, central, with testicular enlargement:
Inheritance x-linked recessive inheritance


Classifications:

Orphanet: 58  
Rare endocrine diseases


External Ids:

Disease Ontology 12 DOID:0111140
OMIM® 57 300888
KEGG 36 H02034
MeSH 44 D003409
ICD10 32 E03.1
ICD10 via Orphanet 33 E03.1
Orphanet 58 ORPHA329235
SNOMED-CT via HPO 68 40930008

Summaries for Hypothyroidism, Central, with Testicular Enlargement

OMIM® : 57 Central hypothyroidism and testicular enlargement (CHTE) is characterized by central hypothyroidism, delayed pubertal testosterone rise, adult macroorchidism, variable prolactin deficiency, and occasional transient partial GH deficiency. Some carrier females also exhibit central hypothyroidism and mild prolactin deficiency. Inter- and intrafamilial variability has been observed (Joustra et al., 2016). (300888) (Updated 05-Mar-2021)

MalaCards based summary : Hypothyroidism, Central, with Testicular Enlargement, also known as hypothyroidism, central, and testicular enlargement, is related to central congenital hypothyroidism and hypothyroidism, congenital, nongoitrous, 4. An important gene associated with Hypothyroidism, Central, with Testicular Enlargement is IGSF1 (Immunoglobulin Superfamily Member 1), and among its related pathways/superpathways is Glucocorticoid receptor regulatory network. Affiliated tissues include thyroid, testis and pituitary, and related phenotypes are hypothyroidism and overweight

Disease Ontology : 12 A syndrome characterized by hypothyroidism that is present at birth, delayed testosterone increase in puberty, and testicular enlargement in adulthood that has material basis in mutation of the IGSF1 gene on chromosome Xq26.

KEGG : 36 Central hypothyroidism and testicular enlargement is a novel X-linked disorder in which loss-of-function mutations in IGSF1. It causes central hypothyroidism, testis enlargement, and variable prolactin and growth hormone deficiency.

UniProtKB/Swiss-Prot : 73 Hypothyroidism, central, and testicular enlargement: A disorder characterized by insufficient thyroid gland stimulation by thyroid stimulating hormone (TSH), resulting from hypothalamic and/or pituitary dysfunction. CHTE patients have delayed testosterone increase at puberty with normal testosterone levels in adulthood, normal testicular volume in childhood and enlarged testicles in adulthood.

Wikipedia : 74 Immunoglobulin superfamily, member 1 is a plasma membrane glycoprotein encoded by the IGSF1 gene, which... more...

Related Diseases for Hypothyroidism, Central, with Testicular Enlargement

Diseases related to Hypothyroidism, Central, with Testicular Enlargement via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 64)
# Related Disease Score Top Affiliating Genes
1 central congenital hypothyroidism 30.3 TSHB TRHR
2 hypothyroidism, congenital, nongoitrous, 4 29.1 TSHB PROP1 PRL POU1F1
3 pituitary gland disease 28.8 TSHB TRH PROP1 PRL POU1F1
4 hypothyroidism 28.4 TSHB TRHR TRH PROP1 PRL POU1F1
5 congenital hypothyroidism 28.3 TSHB TRHR TRH PRL POU1F1 IGSF1
6 growth hormone deficiency 10.3
7 thyroid hormone resistance, selective pituitary 10.1 TSHB TRH
8 thyroid hormone resistance, generalized, autosomal dominant 10.1 TSHB TRH
9 allan-herndon-dudley syndrome 10.1 TSHB TRH
10 hypothyroidism, congenital, nongoitrous, 1 10.0 TSHB DUOXA2
11 hypothyroidism due to deficient transcription factors involved in pituitary development or function 10.0 PROP1 POU1F1
12 body mass index quantitative trait locus 11 10.0
13 body mass index quantitative trait locus 9 10.0
14 body mass index quantitative trait locus 8 10.0
15 body mass index quantitative trait locus 1 10.0
16 body mass index quantitative trait locus 4 10.0
17 body mass index quantitative trait locus 10 10.0
18 body mass index quantitative trait locus 7 10.0
19 body mass index quantitative trait locus 12 10.0
20 body mass index quantitative trait locus 14 10.0
21 body mass index quantitative trait locus 18 10.0
22 body mass index quantitative trait locus 19 10.0
23 neonatal jaundice 10.0
24 combined pituitary hormone deficiencies, genetic forms 10.0 PROP1 POU1F1
25 adamantinous craniopharyngioma 10.0 PROP1 POU1F1
26 isolated growth hormone deficiency, type ii 10.0 PROP1 POU1F1
27 generalized resistance to thyroid hormone 9.9 TRH PRL
28 adenohypophysitis 9.9 TRH PRL
29 lactocele 9.9 TRH PRL
30 acidophil adenoma 9.9 TRH PRL
31 chromophobe adenoma 9.9 TRH PRL
32 pituitary infarct 9.9 TRH PRL
33 borjeson-forssman-lehmann syndrome 9.9 PROP1 POU1F1
34 mixed cerebral palsy 9.9 TRH PRL
35 tsh producing pituitary tumor 9.9 TSHB PRL
36 hyperpituitarism 9.9 TRH PRL
37 melancholia 9.9 TRH PRL
38 pseudohypoparathyroidism, type ia 9.8 TRH PRL
39 pseudohypoparathyroidism 9.8 TRH PRL
40 diabetes insipidus, neurohypophyseal 9.8 TRH PRL
41 functioning pituitary adenoma 9.8 TRH PRL
42 pituitary tumors 9.8 PROP1 PRL
43 pituitary-dependent cushing's disease 9.8 TRHR TRH PRL
44 endogenous depression 9.7 TRH PRL
45 hyperthyroidism 9.7 TRHR TRH PRL
46 pituitary hypoplasia 9.7 PRL POU1F1
47 hypothalamic disease 9.7 TSHB TRH PRL
48 hyperprolactinemia 9.7 TRH PRL
49 acromegaly 9.7 TRHR TRH PRL
50 goiter 9.7 TRH PRL DUOXA2

Graphical network of the top 20 diseases related to Hypothyroidism, Central, with Testicular Enlargement:



Diseases related to Hypothyroidism, Central, with Testicular Enlargement

Symptoms & Phenotypes for Hypothyroidism, Central, with Testicular Enlargement

Human phenotypes related to Hypothyroidism, Central, with Testicular Enlargement:

31
# Description HPO Frequency HPO Source Accession
1 hypothyroidism 31 HP:0000821
2 overweight 31 HP:0025502

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Neurologic Central Nervous System:
fatigue
motor delay (in some patients)
speech delay (in some patients)
clumsiness (in some patients)
neonatal hypothermia (rare)

Growth Weight:
overweight
increased birth weight

Endocrine Features:
decreased serum prolactin
low free t4
hypothyroidism, central
elevated or inappropriately normal thyroid stimulating hormone (tsh)
diminished tsh response to trh stimulation
more
Genitourinary External Genitalia Male:
normal testicular volume in childhood
enlarged testicles in adulthood

Skin Nails Hair Skin:
prolonged neonatal jaundice

Neurologic Behavioral Psychiatric Manifestations:
attention deficit disorder

Growth Height:
delayed growth spurt in puberty
average height in adulthood

Clinical features from OMIM®:

300888 (Updated 05-Mar-2021)

MGI Mouse Phenotypes related to Hypothyroidism, Central, with Testicular Enlargement:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 endocrine/exocrine gland MP:0005379 9.43 IGSF1 POU1F1 PRL PROP1 TRH TRHR
2 reproductive system MP:0005389 9.1 IGSF1 POU1F1 PRL PROP1 TRHR TSHB

Drugs & Therapeutics for Hypothyroidism, Central, with Testicular Enlargement

Search Clinical Trials , NIH Clinical Center for Hypothyroidism, Central, with Testicular Enlargement

Genetic Tests for Hypothyroidism, Central, with Testicular Enlargement

Genetic tests related to Hypothyroidism, Central, with Testicular Enlargement:

# Genetic test Affiliating Genes
1 Hypothyroidism, Central, and Testicular Enlargement 29 IGSF1

Anatomical Context for Hypothyroidism, Central, with Testicular Enlargement

MalaCards organs/tissues related to Hypothyroidism, Central, with Testicular Enlargement:

40
Thyroid, Testis, Pituitary

Publications for Hypothyroidism, Central, with Testicular Enlargement

Articles related to Hypothyroidism, Central, with Testicular Enlargement:

(show all 11)
# Title Authors PMID Year
1
A novel IGSF1 mutation in a large Irish kindred highlights the need for familial screening in the IGSF1 deficiency syndrome. 57 6
30086211 2018
2
Familial Central Hypothyroidism Caused by a Novel IGSF1 Gene Mutation. 57 6
27310681 2016
3
Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement. 57 6
23143598 2012
4
Identification of an IGSF1-specific deletion in a five-generation pedigree with X-linked Central Hypothyroidism without macroorchidism. 57
27146357 2016
5
IGSF1 Deficiency: Lessons From an Extensive Case Series and Recommendations for Clinical Management. 57
26840047 2016
6
The IGSF1 deficiency syndrome: characteristics of male and female patients. 57
24108313 2013
7
DUOX2 Mutations Are Associated With Congenital Hypothyroidism With Ectopic Thyroid Gland. 61
28666341 2017
8
The NEAT Domain-Containing Proteins of Clostridium perfringens Bind Heme. 61
27637108 2016
9
Microwave spectra of the deuterium isotopologues of cis-hexatriene and a semiexperimental equilibrium structure. 61
23237234 2013
10
Substituent effects in the interconversion of phenylcarbene, bicyclo[4.1.0]hepta-2,4,6-triene, and 1,2,4,6-cycloheptatetraene. 61
11950298 2002
11
Mixed submerged fermentation with two filamentous fungi for cellulolytic and xylanolytic enzyme production. 61
12018234 2002

Variations for Hypothyroidism, Central, with Testicular Enlargement

ClinVar genetic disease variations for Hypothyroidism, Central, with Testicular Enlargement:

6 (show all 20)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 IGSF1 NM_001555.5(IGSF1):c.2123_2149del (p.Ala708_Lys716del) Deletion Pathogenic 39849 rs1556181091 X:130412001-130412027 X:131278027-131278053
2 IGSF1 NM_001555.5(IGSF1):c.2916G>A (p.Trp972Ter) SNV Pathogenic 39850 rs398122919 X:130409720-130409720 X:131275746-131275746
3 IGSF1 NM_001555.5(IGSF1):c.2233del (p.Glu745fs) Deletion Pathogenic 39851 rs398122920 X:130411917-130411917 X:131277943-131277943
4 IGSF1 NM_001555.5(IGSF1):c.2573C>T (p.Ser858Phe) SNV Pathogenic 39852 rs397514622 X:130410948-130410948 X:131276974-131276974
5 IGSF1 NM_001555.5(IGSF1):c.2303T>C (p.Leu768Pro) SNV Pathogenic 689655 rs1603404413 X:130411847-130411847 X:131277873-131277873
6 IGSF1 NM_001555.5(IGSF1):c.3581dup (p.Glu1195fs) Duplication Pathogenic 39853 rs398122921 X:130408742-130408743 X:131274768-131274769
7 IGSF1 NM_001555.5(IGSF1):c.2268dup (p.Arg757fs) Duplication Pathogenic 689654 rs1603404421 X:130411881-130411882 X:131277907-131277908
8 IGSF1 NM_001555.5(IGSF1):c.2407dup (p.His803fs) Duplication Pathogenic 807432 rs1603404297 X:130411113-130411114 X:131277139-131277140
9 FANCC NM_000136.3(FANCC):c.996+979_996+983del Deletion Uncertain significance 929812 9:97886385-97886389 9:95124103-95124107
10 FANCC NM_000136.3(FANCC):c.996+1056C>A SNV Likely benign 929813 9:97886312-97886312 9:95124030-95124030
11 FANCC NM_000136.3(FANCC):c.996+1752A>G SNV Likely benign 929814 9:97885616-97885616 9:95123334-95123334
12 FANCB NM_001018113.3(FANCB):c.-70-246C>T SNV Likely benign 691297 rs5935816 X:14883948-14883948 X:14865826-14865826
13 FANCB NM_001018113.3(FANCB):c.951+129A>C SNV Likely benign 691303 rs2375729 X:14882553-14882553 X:14864431-14864431
14 FANCB NM_001018113.3(FANCB):c.2166-186T>C SNV Likely benign 691312 rs6527027 X:14862289-14862289 X:14844167-14844167
15 FANCB NM_001018113.3(FANCB):c.2166-176A>G SNV Likely benign 691313 rs6527026 X:14862279-14862279 X:14844157-14844157
16 FANCB NM_001018113.3(FANCB):c.-173G>C SNV Likely benign 368036 rs2188383 X:14887147-14887147 X:14869025-14869025
17 FANCB NM_001018113.3(FANCB):c.1327-10T>C SNV Likely benign 93467 rs2905223 X:14868806-14868806 X:14850684-14850684
18 IGSF1 NM_001555.5(IGSF1):c.2556T>C (p.Tyr852=) SNV Benign 257591 rs4830219 X:130410965-130410965 X:131276991-131276991
19 IGSF1 NM_001555.5(IGSF1):c.1347A>G (p.Glu449=) SNV Benign 257590 rs1128617 X:130415818-130415818 X:131281844-131281844
20 IGSF1 NM_001555.5(IGSF1):c.948G>A (p.Val316=) SNV Benign 257593 rs5932877 X:130416958-130416958 X:131282984-131282984

UniProtKB/Swiss-Prot genetic disease variations for Hypothyroidism, Central, with Testicular Enlargement:

73
# Symbol AA change Variation ID SNP ID
1 IGSF1 p.Ser765Asn VAR_069269
2 IGSF1 p.Ser858Phe VAR_069270 rs397514622
3 IGSF1 p.Cys942Arg VAR_069271

Expression for Hypothyroidism, Central, with Testicular Enlargement

Search GEO for disease gene expression data for Hypothyroidism, Central, with Testicular Enlargement.

Pathways for Hypothyroidism, Central, with Testicular Enlargement

Pathways related to Hypothyroidism, Central, with Testicular Enlargement according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.54 PRL POU1F1

GO Terms for Hypothyroidism, Central, with Testicular Enlargement

Biological processes related to Hypothyroidism, Central, with Testicular Enlargement according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 hormone-mediated signaling pathway GO:0009755 8.62 TSHB TRH

Molecular functions related to Hypothyroidism, Central, with Testicular Enlargement according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 hormone activity GO:0005179 8.8 TSHB TRH PRL

Sources for Hypothyroidism, Central, with Testicular Enlargement

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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