Central Precocious Puberty (CPP)

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

Aliases & Classifications for Central Precocious Puberty

MalaCards integrated aliases for Central Precocious Puberty:

Name: Central Precocious Puberty 25 58 36 39 17
Cpp 25 58
Gonadotropin-Dependent Precocious Puberty 25
Gonadotropin-Dependant Precocious Puberty 58
Precocious Puberty, Central 71


Orphanet epidemiological data:

central precocious puberty
Inheritance: Autosomal dominant,Not applicable; Age of onset: Childhood,Infancy; Age of death: normal life expectancy;


Orphanet: 58  
Rare gynaecological and obstetric diseases
Rare endocrine diseases

External Ids:

KEGG 36 H02018
ICD10 via Orphanet 33 E22.8
UMLS via Orphanet 72 C0342543
Orphanet 58 ORPHA759
UMLS 71 C0342543

Summaries for Central Precocious Puberty

Genetics Home Reference : 25 Central precocious puberty is a condition that causes early sexual development in girls and boys. While puberty normally starts between ages 8 and 13 in girls and between ages 9 and 14 in boys, girls with central precocious puberty begin exhibiting signs before age 8, and boys with this disorder begin before age 9. Signs of puberty include development of pubic and underarm hair, a rapid increase in height (commonly referred to as a "growth spurt"), acne, and underarm odor. Girls also develop breasts and begin their menstrual periods. Boys have growth of the penis and testes and deepening of the voice. Because of the early growth spurt, children with central precocious puberty may be taller than their peers; however, they may stop growing abnormally early. Without proper treatment, some affected individuals are shorter in adulthood compared with other members of their family. Developing ahead of their peers can be emotionally difficult for affected individuals and may lead to psychological and behavioral problems.

MalaCards based summary : Central Precocious Puberty, also known as cpp, is related to idiopathic central precocious puberty and hypothalamic hamartomas. An important gene associated with Central Precocious Puberty is KISS1R (KISS1 Receptor), and among its related pathways/superpathways are NF-KappaB Family Pathway and G-protein signaling RAC1 in cellular process. The drugs Megestrol acetate and Leuprolide have been mentioned in the context of this disorder. Affiliated tissues include pituitary, testes and bone, and related phenotypes are isosexual precocious puberty and increased circulating gonadotropin level

KEGG : 36 Central precocious puberty is caused by early maturation of the hypothalamic-pituitary-gonadal axis. Recently, kisspeptin receptor (KISS1R) and its ligand, kisspeptin, were described as an excitatory neuroregulator system for the secretion of gonadotropin-releasing hormone (GnRH). Mutations of the KISS1R gene were identified in patients with impaired pubertal development. It has also been reported that central precocious puberty caused by mutations in the imprinted gene MKRN3.

Related Diseases for Central Precocious Puberty

Diseases in the Precocious Puberty family:

Precocious Puberty, Central, 1 Precocious Puberty, Central, 2
Central Precocious Puberty Secondary Central Precocious Puberty
Rare Precocious Puberty

Diseases related to Central Precocious Puberty via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 303)
# Related Disease Score Top Affiliating Genes
1 idiopathic central precocious puberty 32.8 MKRN3 KISS1R KISS1 IGF1
2 hypothalamic hamartomas 31.9 KISS1R KISS1 GNRH1
3 precocious puberty 31.3 MKRN3 KISS1R KISS1 GNRH1 GH1
4 traumatic brain injury 30.4 IGF1 GH1
5 insulin-like growth factor i 30.4 IGF1 GH1
6 polycystic ovary syndrome 30.2 IGF1 GNRH1 GH1
7 sexual disorder 30.1 IGF1 GNRH1
8 hyperandrogenism 30.0 IGF1 GNRH1 GH1
9 mccune-albright syndrome 30.0 IGF1 GH1
10 pseudohypoparathyroidism, type ia 29.9 IGF1 GH1
11 pituitary tumors 29.9 IGF1 GH1
12 hyperprolactinemia 29.8 IGF1 GNRH1 GH1
13 fibrous dysplasia 29.8 IGF1 GH1
14 empty sella syndrome 29.6 IGF1 GNRH1 GH1
15 prader-willi syndrome 29.6 MKRN3 IGF1 GNRH1 GH1
16 hypothyroidism 29.4 IGF1 GNRH1 GH1
17 hypogonadism 29.4 KISS1R KISS1 IGF1 GNRH1
18 septooptic dysplasia 29.4 IGF1 GNRH1 GH1
19 pituitary adenoma, prolactin-secreting 29.4 IGF1 GNRH1 GH1
20 pituitary adenoma 29.4 IGF1 GNRH1 GH1
21 hypogonadotropic hypogonadism 29.4 MKRN3 KISS1R KISS1 GNRH1
22 craniopharyngioma 29.4 IGF1 GNRH1 GH1
23 hyperinsulinism 29.3 IGF1 GNRH1 GH1
24 conn's syndrome 29.3 IGF1 GNRH1 GH1
25 normosmic congenital hypogonadotropic hypogonadism 29.3 KISS1R KISS1 GNRH1
26 precocious puberty, male-limited 29.0 MKRN3 KISS1R KISS1 GNRH1
27 cryptorchidism, unilateral or bilateral 28.8 KISS1R KISS1 IGF1 GNRH1
28 kallmann syndrome 28.8 MKRN3 KISS1R KISS1 GNRH1
29 secondary central precocious puberty 12.7
30 papilloma of choroid plexus 12.3
31 precocious puberty, central, 2 12.0
32 precocious puberty, central, 1 11.9
33 chondrocalcinosis 2 11.4
34 atypical choroid plexus papilloma 11.2
35 congenital heart defects, hamartomas of tongue, and polysyndactyly 10.7
36 prostatitis 10.7
37 body mass index quantitative trait locus 1 10.7
38 lipoid congenital adrenal hyperplasia 10.6
39 head injury 10.4
40 dental caries 10.4
41 growth hormone deficiency 10.4
42 enamel erosion 10.4
43 neurofibromatosis, type ii 10.4
44 brain injury 10.3
45 hydrocephalus 10.3
46 ovarian cyst 10.3
47 neurofibromatosis 10.3
48 chronic pain 10.3
49 panic disorder 10.3
50 williams-beuren syndrome 10.2

Graphical network of the top 20 diseases related to Central Precocious Puberty:

Diseases related to Central Precocious Puberty

Symptoms & Phenotypes for Central Precocious Puberty

Human phenotypes related to Central Precocious Puberty:

58 31 (show all 15)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 isosexual precocious puberty 58 31 obligate (100%) Obligate (100%) HP:0008236
2 increased circulating gonadotropin level 58 31 frequent (33%) Frequent (79-30%) HP:0000837
3 abnormality of secondary sexual hair 58 31 frequent (33%) Frequent (79-30%) HP:0009888
4 proportionate short stature 58 31 frequent (33%) Frequent (79-30%) HP:0003508
5 overgrowth 58 31 frequent (33%) Frequent (79-30%) HP:0001548
6 accelerated bone age after puberty 58 31 frequent (33%) Frequent (79-30%) HP:0002805
7 premature thelarche 58 31 frequent (33%) Frequent (79-30%) HP:0010314
8 acne 58 31 occasional (7.5%) Occasional (29-5%) HP:0001061
9 obesity 58 31 occasional (7.5%) Occasional (29-5%) HP:0001513
10 prenatal maternal abnormality 58 31 occasional (7.5%) Occasional (29-5%) HP:0002686
11 hypothalamic hamartoma 58 31 occasional (7.5%) Occasional (29-5%) HP:0002444
12 hydrocephalus 58 31 very rare (1%) Very rare (<4-1%) HP:0000238
13 meningitis 58 31 very rare (1%) Very rare (<4-1%) HP:0001287
14 cafe-au-lait spot 58 31 very rare (1%) Very rare (<4-1%) HP:0000957
15 increased body weight 58 Frequent (79-30%)

MGI Mouse Phenotypes related to Central Precocious Puberty:

# Description MGI Source Accession Score Top Affiliating Genes
1 renal/urinary system MP:0005367 8.92 GNRH1 IGF1 KISS1 KISS1R

Drugs & Therapeutics for Central Precocious Puberty

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

(show all 25)
# Name Status Phase Clinical Trials Cas Number PubChem Id
Megestrol acetate Approved, Investigational, Vet_approved Phase 4 595-33-5 11683
Leuprolide Approved, Investigational Phase 4 53714-56-0 657181 3911
Medroxyprogesterone acetate Approved, Investigational Phase 4 71-58-9
4 Triptorelin Pamoate Phase 4
5 Prolactin Release-Inhibiting Factors Phase 4
6 Central Nervous System Stimulants Phase 4
Megestrol Phase 4 3562-63-8 19090 3080587
8 Antineoplastic Agents, Hormonal Phase 4
9 Contraceptive Agents Phase 4
10 Contraceptives, Oral Phase 4
11 Progestins Phase 4
12 Contraceptive Agents, Male Phase 4
Medroxyprogesterone Phase 4 520-85-4 10631
14 Pharmaceutical Solutions Phase 3
Testolactone Approved, Investigational Phase 2 968-93-4 13769
Testosterone Approved, Experimental, Investigational Phase 2 58-22-0, 481-30-1 10204 6013
Spironolactone Approved Phase 2 52-01-7, 1952-01-7 5833
Deslorelin Investigational, Vet_approved Phase 2 57773-65-6
19 Hormones Phase 2
20 Hormone Antagonists Phase 2
21 Mineralocorticoids Phase 2
22 Mineralocorticoid Receptor Antagonists Phase 2
23 diuretics Phase 2
24 Diuretics, Potassium Sparing Phase 2
25 Tin Fluorides

Interventional clinical trials:

(show all 24)
# Name Status NCT ID Phase Drugs
1 Analysis of Body Mass Index in Central Precocious Puberty(CPP) Patients Treated With Leuprolide Acetate Unknown status NCT02974270 Phase 4 Leuprolide
2 Triptorelin Acetate Utilization for the Early Diagnosis of Central Precocious Puberty (CPP) in Girls. Unknown status NCT01278290 Phase 4 Triptorelin acetate and Gonadorelin acetate;Gonadorelin acetate and Triptorelin acetate
3 Analysis of Genetic and Environmental Parameters Influencing Growth Rate of Precocious Puberty Children Unknown status NCT00438217 Phase 4 Triptorelin (GnRH agonists);Leuprolide (GnRH agonists)
4 Multi-site Study of Comprehensive Treatment for Children Precocious Puberty Completed NCT02920515 Phase 4 Triptorlin or Leuprorelin;Zhibo dihuang pills;Dabu ying pills
5 The Phase 4 Clinical Trial to Evaluate the Efficacy and Safety of Luphere Depot Inj. 3.75mg(Leuprolide Acetate 3.75mg) in Patients With Precocious Puberty; A Single, Open, Multi-center, Prospective Study Completed NCT01634321 Phase 4 Luphere depot 3.75mg(Leuprolide acetate 3.75mg)
6 A Multicenter, Open, Prospective Study to Evaluate the Safety and Efficacy of Leuprorelin Acetate DPS (Leuplin DPS) Treatment Quarterly in Patients With Central Precocious Puberty Completed NCT03316482 Phase 4 Leuplin DPS 11.25mg
7 An Open Label, Multicenter Study to Assess the Safety and Efficacy of Leuprorelin in the Treatment of Central Precocious Puberty Completed NCT02427958 Phase 4 Leuprorelin
8 Evidence-based Medical Research on the Treatment of Children's Rapid Progressive Central Precocious Puberty With Integrative Chinese and Western Medicine Recruiting NCT03963752 Phase 4 Ziyinxiehuo Granules Herbs;Megestrol Acetate Tablet;Leuprorelin Acetate 3.75mg Injection
9 Initiation of Medical Menopause With Depot Leuprolide Acetate vs Depot Leuprolide Acetate Plus Medroxyprogesterone Acetate: A Pilot Randomized Terminated NCT01776203 Phase 4 Medroxyprogesterone 17-Acetate
10 An Open-label, Single Arm, Multicenter Study on the Efficacy, Safety, and Pharmacokinetics of Leuprolide Acetate 45 mg for Injectable Suspension Controlled Release in Subjects With Central (Gonadotropin-Dependent) Precocious Puberty Completed NCT02452931 Phase 3 Leuprolide Acetate 45 mg
11 An Open-label, Non-comparative, Multicenter Study on the Efficacy, Safety, and Pharmacokinetics of Triptorelin Pamoate (Embonate) 22.5 mg 6-month Formulation in Patients Suffering From Central (Gonadotropin-dependent) Precocious Puberty Completed NCT01467882 Phase 3 Triptorelin
12 A Phase 3, Randomized, Multi-Center, Open-Label Study to Evaluate the Efficacy and Safety of Leuprolide Acetate 11.25 and 30 mg Formulations in Children With Central Precocious Puberty Completed NCT00635817 Phase 3 Leuprolide acetate 11.25 mg;Leuprolide acetate 30 mg
13 A 36 Month, Multi-Center, Open-Label Extension Study to Evaluate the Safety of Leuprolide Acetate 11.25 mg and 30 mg Formulations in Children With Central Precocious Puberty Completed NCT00667446 Phase 3 Leuprolide Acetate 3 Month Depot
14 Study of Lupron Depot In The Treatment of Central Precocious Puberty Completed NCT00660010 Phase 3 Lupron (leuprolide acetate)
15 Phase III, Open-Label Study to Evaluate Efficacy and Safety of Histrelin Subdermal Implant in Children With Central Precocious Puberty Completed NCT00779103 Phase 3 Histrelin Subcutaneous Implant
16 A Phase 3, Multicenter, Open-Label, Two-Part Study to Evaluate the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Leuprolide Acetate 45mg 6-Month Depot Formulation in Children With Central Precocious Puberty (CPP) Recruiting NCT03695237 Phase 3 Leuprolide Acetate (LA)
17 3 Months, Open-Label, Parallel-Group Study of the Pharmacodynamics, Pharmacokinetics and Safety of TAP-144SR 1-month Depot Gelatin-Free vs. Gelatin-Containing Formulation in Female Patients With Uterine Fibroids Completed NCT00776074 Phase 2 Leuprorelin (GF);Leuprorelin (GC)
18 Spironolactone and Testolactone Treatment of Boys With Familial Isosexual Precocious Puberty Completed NCT00001202 Phase 2 Spironolactone;Testolactone;Deslorelin
19 The LUCINDA Trial: LeUprolide Plus Cholinesterase Inhibition to Reduce Neurological Decline in Alzheimer's Recruiting NCT03649724 Phase 2 Placebo;Eligard 22.5Mg Suspension for Injection
20 Influence of Early Adiposity Rebound, Genetic Polymorphisms and GnRHa Treatment on Long-term Outcome of Girls With Idiopathic Central Precocious Puberty. Unknown status NCT02790112
21 Qualitative Assessment of the Psychosocial Impact of Early Puberty in Girls Aged 6 to 8 Years Completed NCT01679925
22 An Observational, Retrospective Study to Evaluate the Long Term Safety and Effectiveness of Leuprorelin in the Treatment of Central Precocious Puberty Completed NCT02993926 Enantone;GnRH agonist
23 COPENHAGEN Minipuberty Study Active, not recruiting NCT02784184
24 Markers of Adequate Pubertal Suppression During Supprelin LA Therapy for Central Precocious Puberty Terminated NCT02006680

Search NIH Clinical Center for Central Precocious Puberty

Genetic Tests for Central Precocious Puberty

Anatomical Context for Central Precocious Puberty

MalaCards organs/tissues related to Central Precocious Puberty:

Pituitary, Testes, Bone, Breast, Brain, Pineal, Ovary

Publications for Central Precocious Puberty

Articles related to Central Precocious Puberty:

(show top 50) (show all 1049)
# Title Authors PMID Year
Molecular Screening of MKRN3, DLK1, and KCNK9 Genes in Girls with Idiopathic Central Precocious Puberty. 61 6
28672280 2017
Mutations in the maternally imprinted gene MKRN3 are common in familial central precocious puberty. 61 6
26431553 2016
Central precocious puberty caused by mutations in the imprinted gene MKRN3. 6 61
23738509 2013
A GPR54-activating mutation in a patient with central precocious puberty. 61 6
18272894 2008
Intracranial Epidural Abscess in a 9-Year-Old Boy With Precocious Puberty and Use of Continuous Positive Airway Pressure. 61
32223497 2020
Heterozygous deletions in MKRN3 cause central precocious puberty without Prader-Willi Syndrome. 61
32480405 2020
Pretreatment Endocrine Disorders Due to Optic Pathway Gliomas in Pediatric Neurofibromatosis Type 1: Multicenter Study. 61
32294191 2020
Telomere length is not altered in girls with idiopathic central precocious puberty treated with a GnRH analog - leuprolide acetate. 61
32496827 2020
Long-term effects of treatment of central precocious puberty with gonadotropin-releasing hormone analogs every three months. 61
32484003 2020
Identification of rare missense mutations in NOTCH2 and HERC2 associated with familial central precocious puberty via whole-exome sequencing. 61
32400230 2020
Rapid progressive central precocious puberty: diagnostic and predictive value of basal sex hormone levels and pelvic ultrasound. 61
32441670 2020
Evaluation of cephalometric characteristics and skeletal maturation of the cervical vertebrae and hand-wrist in girls with central precocious puberty. 61
32475845 2020
MKRN3 inhibits the reproductive axis through actions in kisspeptin-expressing neurons. 61
32407292 2020
Comparison of triptorelin acetate vs triptorelin pamoate in the treatment of Central precocious puberty (CPP): a retrospective study. 61
31441342 2020
Treatment patterns, health resource utilization and costs among central precocious puberty patients treated with leuprolide or histrelin: an examination of the commercial and Medicaid populations. 61
31766907 2020
Challenges in monitoring GnRH analog treatment in central precocious puberty. 61
32401937 2020
Diagnostic value of urinary luteinizing hormone levels in the monitoring of precocious puberty treatment. 61
32236310 2020
Association of Polymorphisms in the Kisspeptin/GPR54 Pathway Genes With Risk of Early Puberty in Chinese Girls. 61
32160304 2020
Girls with premature thelarche younger than 3 years of age might have stimulated LH greater than 10 IU/L. 61
32349465 2020
Inhibin B as a screening tool for early detection and treatment monitoring of central precocious puberty. 61
32162574 2020
Arterial Spin Labeling and Central Precocious Puberty. 61
30397727 2020
An Unusual Presentation of Carney Complex 61
31117334 2020
Treatment with Depot Leuprolide Acetate in Girls with Idiopathic Precocious Puberty: What Parameter should be Used in Deciding on the Initial Dose? 61
31347350 2020
Relationship between final adult height and birth weight after gonadotropin-releasing hormone agonist treatment in girls with central precocious puberty. 61
32252213 2020
A survey of care pathway and health-related quality of life impact for children with central precocious puberty. 61
31778082 2020
Long-Term Outcomes of Treatments for Central Precocious Puberty or Early and Fast Puberty in Chinese Girls. 61
31702013 2020
MKRN3 and KISS1R mutations in precocious and early puberty. 61
32228714 2020
Does the risk of arterial hypertension increase in the course of triptorelin treatment? 61
30091950 2020
Evaluation of serum makorin ring finger protein 3 (MKRN3) levels in girls with idiopathic central precocious puberty and premature thelarche. 61
31852205 2020
Influence of Gonadotropin Hormone Releasing Hormone Agonists on Interhemispheric Functional Connectivity in Girls With Idiopathic Central Precocious Puberty. 61
32082242 2020
Effect of gonadotropin-releasing hormone analog on ovarian reserve in children with central precocious puberty. 61
32005063 2020
Long-term effects of GnRH agonist treatment on body mass index in girls with idiopathic central precocious puberty. 61
31804960 2020
Pathological and Incidental Findings in 403 Taiwanese Girls With Central Precocious Puberty at Initial Diagnosis. 61
32431668 2020
Etiological Spectrum of Precocious Puberty: Data from Northwest India. 61
31937701 2020
Central precocious puberty in a boy with pseudohypoparathyroidism type Ia due to a novel GNAS mutation. 61
32313379 2020
The neuroimaging features of Rathke's cleft cysts in children with endocrine-related diseases. 61
31670263 2020
Management of Systemic Hypersensitivity Reactions to Gonadotropin-Releasing Hormone Analogues during Treatment of Central Precocious Puberty. 61
31972562 2020
The alteration of IGF-1 levels and relationship between IGF-1 levels and growth velocity during GnRH analogue therapy. 61
31809263 2020
Response to Letter to the Editor: "Central Precocious Puberty as a Presenting Sign of Nonclassical Congenital Adrenal Hyperplasia: Clinical Characteristics". 61
31322673 2019
Letter to the Editor: "Central Precocious Puberty as a Presenting Sign of Nonclassical Congenital Adrenal Hyperplasia: Clinical Characteristics". 61
31322677 2019
Brief Behavioral Intervention for Disruptive Behavior in a Child with a Hypothalamic Hamartoma: A Case Report. 61
30470962 2019
Near final adult height, and body mass index in overweight/obese and normal-weight children with idiopathic central precocious puberty and treated with gonadotropin-releasing hormone analogs. 61
31605579 2019
Hypothalamic-Pituitary Disorders in Childhood Cancer Survivors: Prevalence, Risk Factors and Long-Term Health Outcomes. 61
31373627 2019
31967069 2019
A retrospective analysis of the prevalence of imprinting disorders in Estonia from 1998 to 2016. 61
31186545 2019
Understanding the functions of kisspeptin and kisspeptin receptor (Kiss1R) from clinical case studies. 61
30339828 2019
Changes in body mass index in children on gonadotropin-releasing hormone agonist therapy with precocious puberty, early puberty or short stature. 61
31465296 2019
Outcomes of Patients with Central Precocious Puberty due to Loss-of-Function Mutations in MKRN3 Gene After Treatment with Gonadotropin-Releasing Hormone Analog. 61
31671431 2019
Psychological effects of gonadotropin-releasing hormone agonist treatment in girls with central precocious puberty. 61
31415238 2019
Random urinary gonadotropins as a useful initial test for girls with central precocious puberty. 61
31217400 2019

Variations for Central Precocious Puberty

Expression for Central Precocious Puberty

Search GEO for disease gene expression data for Central Precocious Puberty.

Pathways for Central Precocious Puberty

Pathways related to Central Precocious Puberty according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
Show member pathways
12.05 IGF1 GNRH1 GH1
Show member pathways
11.84 IGF1 GNRH1 GH1
Show member pathways
11.54 IGF1 GNRH1 GH1
4 11.13 IGF1 GH1
5 10.82 IGF1 GNRH1 GH1
6 10.61 KISS1R KISS1 GNRH1
7 10.48 IGF1 GNRH1 GH1

GO Terms for Central Precocious Puberty

Biological processes related to Central Precocious Puberty according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 positive regulation of peptidyl-tyrosine phosphorylation GO:0050731 9.26 IGF1 GH1
2 positive regulation of phosphatidylinositol 3-kinase signaling GO:0014068 9.16 IGF1 GH1
3 positive regulation of tyrosine phosphorylation of STAT protein GO:0042531 8.96 IGF1 GH1
4 positive regulation of insulin-like growth factor receptor signaling pathway GO:0043568 8.62 IGF1 GH1

Molecular functions related to Central Precocious Puberty according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 hormone activity GO:0005179 8.8 IGF1 GNRH1 GH1

Sources for Central Precocious Puberty

9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
31 HPO
32 ICD10
33 ICD10 via Orphanet
37 LifeMap
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
54 Novoseek
57 OMIM via Orphanet
61 PubMed
70 Tocris
72 UMLS via Orphanet
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