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 central congenital hypothyroidism and congenital hypothyroidism. An important gene associated with Hypothyroidism, Central, with Testicular Enlargement is IGSF1 (Immunoglobulin Superfamily Member 1). 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.

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 55)
# Related Disease Score Top Affiliating Genes
1 central congenital hypothyroidism 30.6 TSHB TRHR
2 congenital hypothyroidism 28.9 TSHB TRHR PRL POU1F1 DUOXA2
3 hypothyroidism, congenital, nongoitrous, 4 28.8 TSHB PROP1 PRL POU1F1
4 pituitary gland disease 27.8 TSHB TRH PROP1 PRL POU1F1 LHX3
5 hypothyroidism 27.2 TSHB TRHR TRH PROP1 PRL POU1F1
6 growth hormone deficiency 10.2
7 suprasellar meningioma 10.2 TSHB TRH
8 thyroid hormone resistance, selective pituitary 10.2 TSHB TRH
9 thyroid hormone resistance, generalized, autosomal dominant 10.1 TSHB TRH
10 allan-herndon-dudley syndrome 10.1 TSHB TRH
11 neonatal jaundice 10.1
12 generalized resistance to thyroid hormone 10.0 TRH PRL
13 adenohypophysitis 10.0 TRH PRL
14 tsh producing pituitary tumor 10.0 TSHB PRL
15 chromophobe adenoma 10.0 TRH PRL
16 pituitary hormone deficiency, combined, 1 10.0 POU1F1 LHX3
17 pituitary infarct 10.0 TRH PRL
18 acidophil adenoma 10.0 TRH PRL
19 pituitary apoplexy 9.9 TRH PRL
20 hyperpituitarism 9.9 TRH PRL
21 pituitary stalk interruption syndrome 9.9 PRL POU1F1
22 pseudohypoparathyroidism, type ia 9.9 TRH PRL
23 pseudohypoparathyroidism 9.9 TRH PRL
24 pituitary-dependent cushing's disease 9.8 TRHR TRH PRL
25 combined pituitary hormone deficiencies, genetic forms 9.8 PROP1 POU1F1
26 hypothalamic disease 9.8 TSHB TRH PRL
27 diabetes insipidus, neurohypophyseal 9.8 TRH PRL
28 thyroiditis 9.8 TSHB TRH PRL
29 hyperthyroidism 9.8 TRHR TRH PRL
30 adamantinous craniopharyngioma 9.7 PROP1 POU1F1
31 neonatal thyrotoxicosis 9.7 PROP1 LHX3
32 acromegaly 9.7 TRHR TRH PRL
33 functioning pituitary adenoma 9.7 TRH PRL
34 isolated growth hormone deficiency, type ii 9.7 PROP1 POU1F1
35 goiter 9.7 TRH PRL DUOXA2
36 adenoma 9.7 TRH PRL POU1F1
37 endogenous depression 9.7 TRH PRL
38 sheehan syndrome 9.6 PROP1 PRL
39 pituitary hypoplasia 9.6 PRL POU1F1 LHX3
40 hyperprolactinemia 9.5 TRH PRL
41 pituitary tumors 9.5 PROP1 PRL
42 pituitary adenoma, prolactin-secreting 9.5 TRHR TRH PRL POU1F1
43 hypothyroidism due to deficient transcription factors involved in pituitary development or function 9.4 PROP1 POU1F1 LHX3
44 pituitary adenoma 9.4 TSHB TRH PRL POU1F1
45 borjeson-forssman-lehmann syndrome 9.4 PROP1 POU1F1 LHX3
46 isolated growth hormone deficiency 9.4 PROP1 POU1F1 LHX3
47 thyroid gland disease 9.3 TSHB TRH PRL IGSF1 DUOXA2
48 holoprosencephaly 9.2 PROP1 POU1F1 LHX3
49 craniopharyngioma 9.1 TRH PROP1 PRL POU1F1
50 empty sella syndrome 9.0 TRH PROP1 PRL LHX3

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 9.8 IGSF1 LHX3 POU1F1 PRL PROP1 TRH
2 growth/size/body region MP:0005378 9.76 DUOXA2 IGSF1 LHX3 POU1F1 PROP1 TRH
3 nervous system MP:0003631 9.5 ARHGAP36 IGSF1 LHX3 POU1F1 PRL PROP1
4 reproductive system MP:0005389 9.17 IGSF1 LHX3 POU1F1 PRL PROP1 TRHR

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. 6 56
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.2407dup (p.His803fs)duplication Pathogenic 807432 X:130411113-130411114 X:131277139-131277140
2 IGSF1 NM_001555.5(IGSF1):c.2123_2149del (p.Ala708_Lys716del)deletion Pathogenic 39849 rs1556181091 X:130412001-130412027 X:131278027-131278053
3 IGSF1 NM_001555.5(IGSF1):c.2916G>A (p.Trp972Ter)SNV Pathogenic 39850 rs398122919 X:130409720-130409720 X:131275746-131275746
4 IGSF1 NM_001555.5(IGSF1):c.2233del (p.Glu745fs)deletion Pathogenic 39851 rs398122920 X:130411917-130411917 X:131277943-131277943
5 IGSF1 NM_001555.5(IGSF1):c.2573C>T (p.Ser858Phe)SNV Pathogenic 39852 rs397514622 X:130410948-130410948 X:131276974-131276974
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 X:130411881-130411882 X:131277907-131277908
8 IGSF1 NM_001555.5(IGSF1):c.2303T>C (p.Leu768Pro)SNV Pathogenic 689655 X:130411847-130411847 X:131277873-131277873
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

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 9.32 TSHB TRH
2 dorsal/ventral pattern formation GO:0009953 9.26 PROP1 LHX3
3 adenohypophysis development GO:0021984 9.16 PROP1 POU1F1
4 somatotropin secreting cell differentiation GO:0060126 8.96 PROP1 POU1F1
5 pituitary gland development GO:0021983 8.8 PROP1 POU1F1 LHX3

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

# Name GO ID Score Top Affiliating Genes
1 RNA polymerase II transcription factor binding GO:0001085 8.96 POU1F1 LHX3
2 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
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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