MCID: PRC038
MIFTS: 42

Precocious Puberty, Male-Limited

Categories: Genetic diseases, Endocrine diseases, Rare diseases

Aliases & Classifications for Precocious Puberty, Male-Limited

MalaCards integrated aliases for Precocious Puberty, Male-Limited:

Name: Precocious Puberty, Male-Limited 57 55
Gonadotropin-Independent Familial Sexual Precocity 29 6 40
Testotoxicosis 59 75 73
Leydig Cell Adenoma, Somatic, with Precocious Puberty 57 13
Fmpp 59 75
Familial Gonadotropin-Independent Male-Limited Sexual Precocity 59
Sexual Precocity, Familial, Gonadotropin-Independent 57
Familial Male-Limited Precocious Puberty 59
Familial Male Precocious Puberty 75
Male-Limited Precocious Puberty 59
Precocious Puberty in Males 6
Testotoxicosis, Familial 57
Precocious Puberty, Male 57
Familial Testotoxicosis 73

Characteristics:

Orphanet epidemiological data:

59
familial male-limited precocious puberty
Inheritance: Autosomal dominant; Prevalence: <1/1000000 (Europe); Age of onset: Childhood; Age of death: normal life expectancy;

OMIM:

57
Inheritance:
sex-limited autosomal dominant


HPO:

32
precocious puberty, male-limited:
Inheritance sex-limited autosomal dominant


Classifications:

Orphanet: 59  
Rare endocrine diseases


External Ids:

OMIM 57 176410
Orphanet 59 ORPHA3000
UMLS via Orphanet 74 C0342549 C1504412
ICD10 via Orphanet 34 E30.1
MESH via Orphanet 45 C536961
SNOMED-CT via HPO 69 276411001

Summaries for Precocious Puberty, Male-Limited

OMIM : 57 Familial male precocious puberty is a gonadotropin-independent disorder that is inherited in an autosomal dominant, male-limited pattern. Affected males generally exhibit signs of puberty by age 4 years (Shenker et al., 1993). (176410)

MalaCards based summary : Precocious Puberty, Male-Limited, also known as gonadotropin-independent familial sexual precocity, is related to testotoxicosis and precocious puberty. An important gene associated with Precocious Puberty, Male-Limited is LHCGR (Luteinizing Hormone/Choriogonadotropin Receptor), and among its related pathways/superpathways are G alpha (s) signalling events and Ovarian steroidogenesis. The drugs Anastrozole and Bicalutamide have been mentioned in the context of this disorder. Affiliated tissues include testes and testis, and related phenotypes are precocious puberty and behavioral abnormality

UniProtKB/Swiss-Prot : 75 Familial male precocious puberty: In FMPP the receptor is constitutively activated.

Related Diseases for Precocious Puberty, Male-Limited

Graphical network of the top 20 diseases related to Precocious Puberty, Male-Limited:



Diseases related to Precocious Puberty, Male-Limited

Symptoms & Phenotypes for Precocious Puberty, Male-Limited

Symptoms via clinical synopsis from OMIM:

57
Endocrine:
male-limited sexual precocity
extremely rapid virilization

Lab:
increased gonadotropin-independent gonadal testosterone secretion
low basal and gonadotropin-releasing hormone-induced secretion of luteinizing hormone (lh)
advanced spermatogenesis on testis biopsy
novel plasma stimulator of testicular testosterone

GU:
small testes


Clinical features from OMIM:

176410

Human phenotypes related to Precocious Puberty, Male-Limited:

59 32 (show all 13)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 precocious puberty 59 Very frequent (99-80%)
2 behavioral abnormality 59 Occasional (29-5%)
3 macroorchidism 59 Occasional (29-5%)
4 acne 59 Frequent (79-30%)
5 attention deficit hyperactivity disorder 59 Occasional (29-5%)
6 decreased testicular size 32 HP:0008734
7 long penis 59 Frequent (79-30%)
8 abnormality of the hair 59 Frequent (79-30%)
9 tall stature 59 Very frequent (99-80%)
10 oligospermia 59 Occasional (29-5%)
11 male infertility 59 Very frequent (99-80%)
12 accelerated skeletal maturation 59 Very frequent (99-80%)
13 precocious puberty in males 32 HP:0008185

MGI Mouse Phenotypes related to Precocious Puberty, Male-Limited:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 adipose tissue MP:0005375 8.8 CYP19A1 FSHR LHCGR

Drugs & Therapeutics for Precocious Puberty, Male-Limited

Drugs for Precocious Puberty, Male-Limited (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 24)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Anastrozole Approved, Investigational Phase 2 120511-73-1 2187
2
Bicalutamide Approved Phase 2 90357-06-5 56069 2375
3
Spironolactone Approved Phase 2 1952-01-7, 52-01-7 5833
4
Testolactone Approved, Investigational Phase 2 968-93-4 13769
5
Testosterone Approved, Investigational Phase 2 58-22-0 6013
6 Deslorelin Investigational, Vet_approved Phase 2 57773-65-6
7 Androgen Antagonists Phase 2
8 Androgens Phase 2
9 Antineoplastic Agents, Hormonal Phase 2
10 Aromatase Inhibitors Phase 2
11 Estrogen Antagonists Phase 2
12 Estrogens Phase 2
13 Hormone Antagonists Phase 2
14 Hormones Phase 2
15 Hormones, Hormone Substitutes, and Hormone Antagonists Phase 2
16 Steroid Synthesis Inhibitors Phase 2
17 diuretics Phase 2
18 Diuretics, Potassium Sparing Phase 2
19 Mineralocorticoid Receptor Antagonists Phase 2
20 Mineralocorticoids Phase 2
21 Natriuretic Agents Phase 2
22
Epinephrine Approved, Vet_approved 51-43-4 5816
23
Racepinephrine Approved 329-65-7 838
24 Epinephryl borate

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Pediatrics Testotoxicosis Study [Bicalutamide Anastrozole Treatment for Testotoxicosis] Completed NCT00094328 Phase 2 Bicalutamide;Anastrozole
2 Treatment of Boys With Precocious Puberty Completed NCT00001202 Phase 2 Spironolactone;Testolactone;Deslorelin
3 Natural History Study of Patients With Excess Androgen Enrolling by invitation NCT00250159

Search NIH Clinical Center for Precocious Puberty, Male-Limited

Genetic Tests for Precocious Puberty, Male-Limited

Genetic tests related to Precocious Puberty, Male-Limited:

# Genetic test Affiliating Genes
1 Gonadotropin-Independent Familial Sexual Precocity 29 LHCGR

Anatomical Context for Precocious Puberty, Male-Limited

MalaCards organs/tissues related to Precocious Puberty, Male-Limited:

41
Testes, Testis

Publications for Precocious Puberty, Male-Limited

Articles related to Precocious Puberty, Male-Limited:

# Title Authors Year
1
Gonadotropin-independent familial sexual precocity with premature Leydig and germinal cell maturation (familial testotoxicosis): effects of a potent luteinizing hormone-releasing factor agonist and medroxyprogesterone acetate therapy in four cases. ( 6223935 )
1983

Variations for Precocious Puberty, Male-Limited

UniProtKB/Swiss-Prot genetic disease variations for Precocious Puberty, Male-Limited:

75 (show all 15)
# Symbol AA change Variation ID SNP ID
1 LHCGR p.Ala373Val VAR_003553 rs121912528
2 LHCGR p.Met398Thr VAR_003554 rs121912526
3 LHCGR p.Ala568Val VAR_003555 rs121912534
4 LHCGR p.Met571Ile VAR_003556 rs121912519
5 LHCGR p.Ala572Val VAR_003557 rs121912522
6 LHCGR p.Thr577Ile VAR_003558 rs121912521
7 LHCGR p.Asp578Gly VAR_003559 rs121912518
8 LHCGR p.Leu457Arg VAR_010156 rs121912535
9 LHCGR p.Ile542Leu VAR_010157 rs121912531
10 LHCGR p.Asp564Gly VAR_010159 rs121912540
11 LHCGR p.Ile575Leu VAR_010160
12 LHCGR p.Asp578Glu VAR_010161
13 LHCGR p.Asp578Tyr VAR_010163 rs121912532
14 LHCGR p.Cys581Arg VAR_010164
15 LHCGR p.Leu368Pro VAR_062338 rs121912533

ClinVar genetic disease variations for Precocious Puberty, Male-Limited:

6
(show top 50) (show all 88)
# Gene Variation Type Significance SNP ID Assembly Location
1 LHCGR NM_000233.3(LHCGR): c.1733A> G (p.Asp578Gly) single nucleotide variant Pathogenic rs121912518 GRCh37 Chromosome 2, 48915203: 48915203
2 LHCGR NM_000233.3(LHCGR): c.1733A> G (p.Asp578Gly) single nucleotide variant Pathogenic rs121912518 GRCh38 Chromosome 2, 48688064: 48688064
3 LHCGR NM_000233.3(LHCGR): c.1713G> A (p.Met571Ile) single nucleotide variant Pathogenic rs121912519 GRCh37 Chromosome 2, 48915223: 48915223
4 LHCGR NM_000233.3(LHCGR): c.1713G> A (p.Met571Ile) single nucleotide variant Pathogenic rs121912519 GRCh38 Chromosome 2, 48688084: 48688084
5 LHCGR NM_000233.3(LHCGR): c.1730C> T (p.Thr577Ile) single nucleotide variant Pathogenic rs121912521 GRCh37 Chromosome 2, 48915206: 48915206
6 LHCGR NM_000233.3(LHCGR): c.1730C> T (p.Thr577Ile) single nucleotide variant Pathogenic rs121912521 GRCh38 Chromosome 2, 48688067: 48688067
7 LHCGR NM_000233.3(LHCGR): c.1715C> T (p.Ala572Val) single nucleotide variant Pathogenic rs121912522 GRCh37 Chromosome 2, 48915221: 48915221
8 LHCGR NM_000233.3(LHCGR): c.1715C> T (p.Ala572Val) single nucleotide variant Pathogenic rs121912522 GRCh38 Chromosome 2, 48688082: 48688082
9 LHCGR NM_000233.3(LHCGR): c.1193T> C (p.Met398Thr) single nucleotide variant Pathogenic/Likely pathogenic rs121912526 GRCh37 Chromosome 2, 48915743: 48915743
10 LHCGR NM_000233.3(LHCGR): c.1193T> C (p.Met398Thr) single nucleotide variant Pathogenic/Likely pathogenic rs121912526 GRCh38 Chromosome 2, 48688604: 48688604
11 LHCGR NM_000233.3(LHCGR): c.1118C> T (p.Ala373Val) single nucleotide variant Pathogenic rs121912528 GRCh37 Chromosome 2, 48915818: 48915818
12 LHCGR NM_000233.3(LHCGR): c.1118C> T (p.Ala373Val) single nucleotide variant Pathogenic rs121912528 GRCh38 Chromosome 2, 48688679: 48688679
13 LHCGR NM_000233.3(LHCGR): c.1624A> C (p.Ile542Leu) single nucleotide variant Pathogenic rs121912531 GRCh37 Chromosome 2, 48915312: 48915312
14 LHCGR NM_000233.3(LHCGR): c.1624A> C (p.Ile542Leu) single nucleotide variant Pathogenic rs121912531 GRCh38 Chromosome 2, 48688173: 48688173
15 LHCGR NM_000233.3(LHCGR): c.1103T> C (p.Leu368Pro) single nucleotide variant Pathogenic rs121912533 GRCh37 Chromosome 2, 48915833: 48915833
16 LHCGR NM_000233.3(LHCGR): c.1103T> C (p.Leu368Pro) single nucleotide variant Pathogenic rs121912533 GRCh38 Chromosome 2, 48688694: 48688694
17 LHCGR NM_000233.3(LHCGR): c.1703C> T (p.Ala568Val) single nucleotide variant Pathogenic rs121912534 GRCh37 Chromosome 2, 48915233: 48915233
18 LHCGR NM_000233.3(LHCGR): c.1703C> T (p.Ala568Val) single nucleotide variant Pathogenic rs121912534 GRCh38 Chromosome 2, 48688094: 48688094
19 LHCGR NM_000233.3(LHCGR): c.1370T> G (p.Leu457Arg) single nucleotide variant Pathogenic rs121912535 GRCh37 Chromosome 2, 48915566: 48915566
20 LHCGR NM_000233.3(LHCGR): c.1370T> G (p.Leu457Arg) single nucleotide variant Pathogenic rs121912535 GRCh38 Chromosome 2, 48688427: 48688427
21 LHCGR NM_000233.3(LHCGR): c.1691A> G (p.Asp564Gly) single nucleotide variant Pathogenic rs121912540 GRCh37 Chromosome 2, 48915245: 48915245
22 LHCGR NM_000233.3(LHCGR): c.1691A> G (p.Asp564Gly) single nucleotide variant Pathogenic rs121912540 GRCh38 Chromosome 2, 48688106: 48688106
23 LHCGR NM_000233.3(LHCGR): c.1732G> T (p.Asp578Tyr) single nucleotide variant Likely pathogenic rs121912532 GRCh37 Chromosome 2, 48915204: 48915204
24 LHCGR NM_000233.3(LHCGR): c.1732G> T (p.Asp578Tyr) single nucleotide variant Likely pathogenic rs121912532 GRCh38 Chromosome 2, 48688065: 48688065
25 LHCGR NM_000233.3(LHCGR): c.1065T> C (p.Asp355=) single nucleotide variant Benign rs11125179 GRCh37 Chromosome 2, 48915871: 48915871
26 LHCGR NM_000233.3(LHCGR): c.1065T> C (p.Asp355=) single nucleotide variant Benign rs11125179 GRCh38 Chromosome 2, 48688732: 48688732
27 LHCGR NM_000233.3(LHCGR): c.935A> G (p.Asn312Ser) single nucleotide variant Benign rs2293275 GRCh38 Chromosome 2, 48694236: 48694236
28 LHCGR NM_000233.3(LHCGR): c.935A> G (p.Asn312Ser) single nucleotide variant Benign rs2293275 GRCh37 Chromosome 2, 48921375: 48921375
29 LHCGR NM_000233.3(LHCGR): c.866+8G> A single nucleotide variant Benign rs6755901 GRCh37 Chromosome 2, 48925746: 48925746
30 LHCGR NM_000233.3(LHCGR): c.866+8G> A single nucleotide variant Benign rs6755901 GRCh38 Chromosome 2, 48698607: 48698607
31 LHCGR NM_000233.3(LHCGR): c.*383C> A single nucleotide variant Uncertain significance rs777978092 GRCh38 Chromosome 2, 48687314: 48687314
32 LHCGR NM_000233.3(LHCGR): c.*383C> A single nucleotide variant Uncertain significance rs777978092 GRCh37 Chromosome 2, 48914453: 48914453
33 LHCGR NM_000233.3(LHCGR): c.*360G> A single nucleotide variant Benign rs10495956 GRCh38 Chromosome 2, 48687337: 48687337
34 LHCGR NM_000233.3(LHCGR): c.*360G> A single nucleotide variant Benign rs10495956 GRCh37 Chromosome 2, 48914476: 48914476
35 LHCGR NM_000233.3(LHCGR): c.*281delA deletion Likely benign rs558291070 GRCh38 Chromosome 2, 48687416: 48687416
36 LHCGR NM_000233.3(LHCGR): c.*281delA deletion Likely benign rs558291070 GRCh37 Chromosome 2, 48914555: 48914555
37 LHCGR NM_000233.3(LHCGR): c.*221G> C single nucleotide variant Benign rs62137532 GRCh38 Chromosome 2, 48687476: 48687476
38 LHCGR NM_000233.3(LHCGR): c.*221G> C single nucleotide variant Benign rs62137532 GRCh37 Chromosome 2, 48914615: 48914615
39 LHCGR NM_000233.3(LHCGR): c.*7C> T single nucleotide variant Likely benign rs200256443 GRCh38 Chromosome 2, 48687690: 48687690
40 LHCGR NM_000233.3(LHCGR): c.*7C> T single nucleotide variant Likely benign rs200256443 GRCh37 Chromosome 2, 48914829: 48914829
41 LHCGR NM_000233.3(LHCGR): c.2002A> C (p.Thr668Pro) single nucleotide variant Likely benign rs199807908 GRCh38 Chromosome 2, 48687795: 48687795
42 LHCGR NM_000233.3(LHCGR): c.2002A> C (p.Thr668Pro) single nucleotide variant Likely benign rs199807908 GRCh37 Chromosome 2, 48914934: 48914934
43 LHCGR NM_000233.3(LHCGR): c.606-5C> T single nucleotide variant Likely benign rs78135094 GRCh37 Chromosome 2, 48936166: 48936166
44 LHCGR NM_000233.3(LHCGR): c.606-5C> T single nucleotide variant Likely benign rs78135094 GRCh38 Chromosome 2, 48709027: 48709027
45 LHCGR NM_000233.3(LHCGR): c.-58G> T single nucleotide variant Benign rs10176989 GRCh37 Chromosome 2, 48982868: 48982868
46 LHCGR NM_000233.3(LHCGR): c.-58G> T single nucleotide variant Benign rs10176989 GRCh38 Chromosome 2, 48755729: 48755729
47 LHCGR NM_000233.3(LHCGR): c.*724T> C single nucleotide variant Uncertain significance rs886056145 GRCh38 Chromosome 2, 48686973: 48686973
48 LHCGR NM_000233.3(LHCGR): c.*724T> C single nucleotide variant Uncertain significance rs886056145 GRCh37 Chromosome 2, 48914112: 48914112
49 LHCGR NM_000233.3(LHCGR): c.*273T> C single nucleotide variant Uncertain significance rs886056146 GRCh38 Chromosome 2, 48687424: 48687424
50 LHCGR NM_000233.3(LHCGR): c.*273T> C single nucleotide variant Uncertain significance rs886056146 GRCh37 Chromosome 2, 48914563: 48914563

Expression for Precocious Puberty, Male-Limited

Search GEO for disease gene expression data for Precocious Puberty, Male-Limited.

Pathways for Precocious Puberty, Male-Limited

Pathways related to Precocious Puberty, Male-Limited according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.49 FSHR LHCGR
2 10.82 CYP19A1 FSHR LHCGR
3 10.69 CYP19A1 FSHR
4 10.3 CYP19A1 FSHR LHCGR
5 10.27 FSHR LHCGR

GO Terms for Precocious Puberty, Male-Limited

Biological processes related to Precocious Puberty, Male-Limited according to GeneCards Suite gene sharing:

(show all 12)
# Name GO ID Score Top Affiliating Genes
1 male gonad development GO:0008584 9.51 FSHR LHCGR
2 adenylate cyclase-activating G-protein coupled receptor signaling pathway GO:0007189 9.49 FSHR LHCGR
3 phospholipase C-activating G-protein coupled receptor signaling pathway GO:0007200 9.48 FSHR LHCGR
4 hormone-mediated signaling pathway GO:0009755 9.46 FSHR LHCGR
5 activation of adenylate cyclase activity GO:0007190 9.43 FSHR LHCGR
6 regulation of osteoclast differentiation GO:0045670 9.4 FSHR LHCGR
7 positive regulation of adenylate cyclase activity GO:0045762 9.37 FSHR LHCGR
8 ovulation cycle process GO:0022602 9.32 FSHR LHCGR
9 follicle-stimulating hormone signaling pathway GO:0042699 9.26 FSHR LHCGR
10 primary ovarian follicle growth GO:0001545 9.16 FSHR LHCGR
11 female gonad development GO:0008585 9.13 CYP19A1 FSHR LHCGR
12 uterus development GO:0060065 8.8 CYP19A1 FSHR LHCGR

Molecular functions related to Precocious Puberty, Male-Limited according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 G-protein coupled peptide receptor activity GO:0008528 9.16 FSHR LHCGR
2 protein-hormone receptor activity GO:0016500 8.96 FSHR LHCGR
3 follicle-stimulating hormone receptor activity GO:0004963 8.62 FSHR LHCGR

Sources for Precocious Puberty, Male-Limited

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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