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Precocious puberty, central, 2(CPPB2)

MedGen UID:
815529
Concept ID:
C3809199
Disease or Syndrome
Synonym: CPPB2
 
Gene (location): MKRN3 (15q11.2)
 
Monarch Initiative: MONDO:0014137
OMIM®: 615346

Definition

Early activation of the hypothalamic-pituitary-gonadal axis results in gonadotropin-dependent precocious puberty, also known as central precocious puberty, which is clinically defined by the development of secondary sexual characteristics before the age of 8 years in girls and 9 years in boys. Pubertal timing is influenced by complex interactions among genetic, nutritional, environmental, and socioeconomic factors. The timing of puberty is associated with risks of subsequent disease: earlier age of menarche in girls is associated with increased risk of breast cancer, endometrial cancer, obesity, type 2 diabetes, and cardiovascular disease. Central precocious puberty has also been associated with an increased incidence of conduct and behavior disorders during adolescence (summary by Abreu et al., 2013). For discussion of genetic heterogeneity of central precocious puberty, see CPPB1 (176400). [from OMIM]

Additional description

From MedlinePlus Genetics
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.  https://medlineplus.gov/genetics/condition/central-precocious-puberty

Clinical features

From HPO
Accelerated skeletal maturation
MedGen UID:
154262
Concept ID:
C0545053
Finding
An abnormally increased rate of skeletal maturation. Accelerated skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
Premature pubarche
MedGen UID:
575093
Concept ID:
C0342541
Disease or Syndrome
The onset of growth of pubic hair at an earlier age than normal.
Premature thelarche
MedGen UID:
98416
Concept ID:
C0425772
Finding
Premature development of the breasts.

Professional guidelines

PubMed

Bangalore Krishna K, Klein KO, Eugster EA
Endocrinol Metab Clin North Am 2024 Jun;53(2):229-238. Epub 2024 Feb 18 doi: 10.1016/j.ecl.2024.01.004. PMID: 38677866
Klein DA, Emerick JE, Sylvester JE, Vogt KS
Am Fam Physician 2017 Nov 1;96(9):590-599. PMID: 29094880
Chirico V, Lacquaniti A, Salpietro V, Buemi M, Salpietro C, Arrigo T
J Biol Regul Homeost Agents 2014 Jul-Sep;28(3):367-75. PMID: 25316125

Recent clinical studies

Etiology

Cassio A, Marescotti G, Aversa T, Salerno M, Tornese G, Stancampiano M, Tuli G, Faienza MF, Cavarzere P, Fava D, Parpagnoli M, Bruzzi P, Ibba A, Calcaterra V, Mameli C, Grandone A, Cherubini V, Assirelli V, Franchina F, Capalbo D, Di Mase R, Tamaro G, Cavasin J, Munarin J, Russo G, Wasniewska M; Physiopathology of Growth Processes and Puberty Study Group of the Italian Society for Pediatric Endocrinology and Diabetology
J Clin Endocrinol Metab 2024 Jul 12;109(8):2061-2070. doi: 10.1210/clinem/dgae035. PMID: 38308814Free PMC Article
Canton APM, Tinano FR, Guasti L, Montenegro LR, Ryan F, Shears D, de Melo ME, Gomes LG, Piana MP, Brauner R, Espino-Aguilar R, Escribano-Muñoz A, Paganoni A, Read JE, Korbonits M, Seraphim CE, Costa SS, Krepischi AC, Jorge AAL, David A, Kaisinger LR, Ong KK, Perry JRB, Abreu AP, Kaiser UB, Argente J, Mendonca BB, Brito VN, Howard SR, Latronico AC
Lancet Diabetes Endocrinol 2023 Aug;11(8):545-554. Epub 2023 Jun 26 doi: 10.1016/S2213-8587(23)00131-6. PMID: 37385287Free PMC Article
Liu G, Guo J, Zhang X, Lu Y, Miao J, Xue H
BMC Pediatr 2021 Nov 16;21(1):509. doi: 10.1186/s12887-021-02936-1. PMID: 34784914Free PMC Article
Rosenfield RL
Endocr Rev 2021 Nov 16;42(6):783-814. doi: 10.1210/endrev/bnab009. PMID: 33788946Free PMC Article
Smith CE, Biro FM
Clin Obstet Gynecol 2020 Sep;63(3):491-503. doi: 10.1097/GRF.0000000000000537. PMID: 32482957

Diagnosis

Rapaport R
Endocrinol Metab Clin North Am 2024 Jun;53(2):ix-x. doi: 10.1016/j.ecl.2024.03.001. PMID: 38677873
Brito VN, Canton APM, Seraphim CE, Abreu AP, Macedo DB, Mendonca BB, Kaiser UB, Argente J, Latronico AC
Endocr Rev 2023 Mar 4;44(2):193-221. doi: 10.1210/endrev/bnac020. PMID: 35930274Free PMC Article
Prosperi S, Chiarelli F
Front Endocrinol (Lausanne) 2022;13:1107911. Epub 2023 Jan 9 doi: 10.3389/fendo.2022.1107911. PMID: 36699035Free PMC Article
Rosenfield RL
Endocr Rev 2021 Nov 16;42(6):783-814. doi: 10.1210/endrev/bnab009. PMID: 33788946Free PMC Article
Klein DA, Emerick JE, Sylvester JE, Vogt KS
Am Fam Physician 2017 Nov 1;96(9):590-599. PMID: 29094880

Therapy

Fraga NR, Minaeian N, Kim MS
Pediatr Rev 2024 Feb 1;45(2):74-84. doi: 10.1542/pir.2022-005617. PMID: 38296783
Wit JM
Front Endocrinol (Lausanne) 2021;12:812196. Epub 2021 Dec 16 doi: 10.3389/fendo.2021.812196. PMID: 34975773Free PMC Article
Liu G, Guo J, Zhang X, Lu Y, Miao J, Xue H
BMC Pediatr 2021 Nov 16;21(1):509. doi: 10.1186/s12887-021-02936-1. PMID: 34784914Free PMC Article
Nermoen I, Husebye ES, Myhre AG, Løvås K
Tidsskr Nor Laegeforen 2017 Apr;137(7):540-543. Epub 2017 Apr 4 doi: 10.4045/tidsskr.16.0376. PMID: 28383228
Neely EK, Crossen SS
Curr Opin Obstet Gynecol 2014 Oct;26(5):332-8. doi: 10.1097/GCO.0000000000000099. PMID: 25144596

Prognosis

Wit JM
Front Endocrinol (Lausanne) 2021;12:812196. Epub 2021 Dec 16 doi: 10.3389/fendo.2021.812196. PMID: 34975773Free PMC Article
Urakami T
Minerva Pediatr 2020 Dec;72(6):472-483. Epub 2020 Aug 4 doi: 10.23736/S0026-4946.20.05971-X. PMID: 32748612
Neely EK, Crossen SS
Curr Opin Obstet Gynecol 2014 Oct;26(5):332-8. doi: 10.1097/GCO.0000000000000099. PMID: 25144596
Reiter EO, Norjavaara E
Pediatr Endocrinol Rev 2005 Dec;3(2):77-86. PMID: 16361981
Colaco P
Indian J Pediatr 1997 Mar-Apr;64(2):165-75. doi: 10.1007/BF02752439. PMID: 10771833

Clinical prediction guides

Bangalore Krishna K, Klein KO, Eugster EA
Endocrinol Metab Clin North Am 2024 Jun;53(2):229-238. Epub 2024 Feb 18 doi: 10.1016/j.ecl.2024.01.004. PMID: 38677866
Wit JM
Front Endocrinol (Lausanne) 2021;12:812196. Epub 2021 Dec 16 doi: 10.3389/fendo.2021.812196. PMID: 34975773Free PMC Article
Liu G, Guo J, Zhang X, Lu Y, Miao J, Xue H
BMC Pediatr 2021 Nov 16;21(1):509. doi: 10.1186/s12887-021-02936-1. PMID: 34784914Free PMC Article
Reiter EO, Norjavaara E
Pediatr Endocrinol Rev 2005 Dec;3(2):77-86. PMID: 16361981
Colaco P
Indian J Pediatr 1997 Mar-Apr;64(2):165-75. doi: 10.1007/BF02752439. PMID: 10771833

Recent systematic reviews

Cheng H, Chen D, Gao H
Front Endocrinol (Lausanne) 2023;14:1298374. Epub 2023 Dec 5 doi: 10.3389/fendo.2023.1298374. PMID: 38116317Free PMC Article
Soliman AT, Alaaraj N, De Sanctis V, Hamed N, Alyafei F, Ahmed S
Acta Biomed 2023 Dec 5;94(6):e2023222. doi: 10.23750/abm.v94i6.15316. PMID: 38054666Free PMC Article
Eckert-Lind C, Busch AS, Petersen JH, Biro FM, Butler G, Bräuner EV, Juul A
JAMA Pediatr 2020 Apr 1;174(4):e195881. Epub 2020 Apr 6 doi: 10.1001/jamapediatrics.2019.5881. PMID: 32040143Free PMC Article
Wen Y, Liu SD, Lei X, Ling YS, Luo Y, Liu Q
Int J Environ Res Public Health 2015 Dec 1;12(12):15254-68. doi: 10.3390/ijerph121214974. PMID: 26633449Free PMC Article
Bouras T, Sgouros S
J Neurosurg Pediatr 2011 Jun;7(6):643-9. doi: 10.3171/2011.4.PEDS10503. PMID: 21631203

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