CHTE
MCID: HYP856
MIFTS: 39

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 56
Hypothyroidism, Central, and Testicular Enlargement 56 73 29 13 6
Igsf1 Deficiency Syndrome 12 58 15
Chte 56 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:

56
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 56 300888
KEGG 36 H02034
MeSH 43 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 : 56 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)

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

Disease Ontology : 12 An X-linked recessive disease 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.

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 all 29)
# Related Disease Score Top Affiliating Genes
1 hypothyroidism, congenital, nongoitrous, 4 29.8 TSHB PROP1 POU1F1
2 congenital hypothyroidism 29.6 TSHB POU1F1 DUOXA2
3 pituitary gland disease 29.4 TSHB TRH PROP1 POU1F1
4 hypothyroidism 28.5 TSHB TRHR TRH PROP1 POU1F1 IGSF1
5 growth hormone deficiency 10.2
6 suprasellar meningioma 10.2 TSHB TRH
7 hypothalamic disease 10.1 TSHB TRH
8 neonatal jaundice 10.1
9 central congenital hypothyroidism 10.1
10 thyroid hormone resistance, generalized, autosomal dominant 10.1 TSHB TRH
11 hypothyroidism due to deficient transcription factors involved in pituitary development or function 10.0 PROP1 POU1F1
12 combined pituitary hormone deficiencies, genetic forms 10.0 PROP1 POU1F1
13 congenital hypopituitarism 10.0 PROP1 POU1F1
14 isolated growth hormone deficiency, type ii 10.0 PROP1 POU1F1
15 empty sella syndrome 10.0 TRH PROP1
16 isolated growth hormone deficiency 10.0 PROP1 POU1F1
17 combined pituitary hormone deficiency 9.9 PROP1 POU1F1
18 pituitary adenoma, prolactin-secreting 9.9 TRHR TRH POU1F1
19 pituitary adenoma 9.9 TSHB TRH POU1F1
20 thyroiditis 9.9 TSHB TRH
21 pituitary tumors 9.9 PROP1 POU1F1
22 borjeson-forssman-lehmann syndrome 9.8 PROP1 POU1F1
23 craniopharyngioma 9.7 TRH PROP1 POU1F1
24 pituitary hormone deficiency, combined, 2 9.5 TSHB TRH PROP1 POU1F1
25 amenorrhea 9.4 TRH FSHB
26 kallmann syndrome 9.2 PROP1 IGSF1 FSHB
27 septooptic dysplasia 9.1 TRH PROP1 POU1F1 FSHB
28 hypopituitarism 9.1 TRH PROP1 POU1F1 FSHB
29 acth deficiency, isolated 9.0 TSHB TRHR TRH PROP1 POU1F1 IGSF1

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:

56
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

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

45
# Description MGI Source Accession Score Top Affiliating Genes
1 endocrine/exocrine gland MP:0005379 9.63 FSHB IGSF1 POU1F1 PROP1 TRH TRHR
2 growth/size/body region MP:0005378 9.56 CRAMP1 DUOXA2 IGSF1 POU1F1 PROP1 TRH
3 reproductive system MP:0005389 9.1 FSHB IGSF1 POU1F1 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, Pituitary, Testis

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. 56 6
30086211 2018
2
Familial Central Hypothyroidism Caused by a Novel IGSF1 Gene Mutation. 56 6
27310681 2016
3
Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement. 56 6
23143598 2012
4
Identification of an IGSF1-specific deletion in a five-generation pedigree with X-linked Central Hypothyroidism without macroorchidism. 56
27146357 2016
5
IGSF1 Deficiency: Lessons From an Extensive Case Series and Recommendations for Clinical Management. 56
26840047 2016
6
The IGSF1 deficiency syndrome: characteristics of male and female patients. 56
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 17) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# 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.3581dup (p.Glu1195fs)duplication Pathogenic 39853 rs398122921 X:130408742-130408743 X:131274768-131274769
6 IGSF1 NM_001555.5(IGSF1):c.2268dup (p.Arg757fs)duplication Pathogenic 689654 X:130411881-130411882 X:131277907-131277908
7 IGSF1 NM_001555.5(IGSF1):c.2303T>C (p.Leu768Pro)SNV Pathogenic 689655 X:130411847-130411847 X:131277873-131277873
8 IGSF1 NM_001555.5(IGSF1):c.2407dup (p.His803fs)duplication Pathogenic 807432 X:130411113-130411114 X:131277139-131277140
9 FANCB NM_001018113.3(FANCB):c.2166-176A>GSNV Likely benign 691313 X:14862279-14862279 X:14844157-14844157
10 FANCB NM_001018113.3(FANCB):c.2166-186T>CSNV Likely benign 691312 X:14862289-14862289 X:14844167-14844167
11 FANCB NM_001018113.3(FANCB):c.951+129A>CSNV Likely benign 691303 X:14882553-14882553 X:14864431-14864431
12 FANCB NM_001018113.3(FANCB):c.-70-246C>TSNV Likely benign 691297 X:14883948-14883948 X:14865826-14865826
13 FANCB NM_001018113.3(FANCB):c.1327-10T>CSNV Benign 93467 rs2905223 X:14868806-14868806 X:14850684-14850684
14 IGSF1 NM_001555.5(IGSF1):c.2556T>C (p.Tyr852=)SNV Benign 257591 rs4830219 X:130410965-130410965 X:131276991-131276991
15 IGSF1 NM_001555.5(IGSF1):c.1347A>G (p.Glu449=)SNV Benign 257590 rs1128617 X:130415818-130415818 X:131281844-131281844
16 IGSF1 NM_001555.5(IGSF1):c.948G>A (p.Val316=)SNV Benign 257593 rs5932877 X:130416958-130416958 X:131282984-131282984
17 FANCB NM_001018113.3(FANCB):c.-173G>CSNV Benign 368036 rs2188383 X:14887147-14887147 X:14869025-14869025

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 9.74 TSHB FSHB

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 pituitary gland development GO:0021983 9.32 PROP1 POU1F1
2 peptide hormone processing GO:0016486 9.26 TSHB FSHB
3 adenohypophysis development GO:0021984 9.16 PROP1 POU1F1
4 somatotropin secreting cell differentiation GO:0060126 8.96 PROP1 POU1F1
5 hormone-mediated signaling pathway GO:0009755 8.8 TSHB TRH FSHB

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 FSHB

Sources for Hypothyroidism, Central, with Testicular Enlargement

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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