Gonadotropin dependent precocious puberty in a boy with Prader Willi Syndrome

Objective: Prader-Willi syndrome (PWS) is a rare genetic neuroendocrine disorder characterized by hypotonia, obesity, short stature, and mental retardation. Incomplete or delayed pubertal development as well as premature adrenarche are usually found in PWS, whereas central precocious puberty is rarely seen. Methods: This study reports the clinical, biochemical, and histologic findings in 2 boys with PWS who developed central precocious puberty. Results: Both boys were started on growth hormone therapy during the first years of life according to the PWS indication. They had both bilateral cryptorchidism at birth and had orchidopexy in early childhood. Retrospective histologic analysis of testicular biopsies demonstrated largely normal tissue architecture and germ cell maturation, but severely decreased number of prespermatogonia in one of the patients. Both boys had premature adrenarche around the age of 6. Precocious puberty was diagnosed in both boys with enlargement of testicular volume (>3 mL), signs of virilization and a pubertal response to a gonadotropin-releasing hormone (GnRH) test and they were both treated with GnRH analog. Conclusion: The cases described here displayed typical characteristics for PWS, a considerable heterogeneity of the hypothalamic-pituitary function, as well as testicular histology. Central precocious puberty is extremely rare in PWS boys, but growth hormone treatment may play a role in the pubertal timing.

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Precocious puberty in the male offspring of a mother and daughter with the Prader-Willi syndrome

American Journal of Medical Genetics ◽

10.1002/ajmg.1320260333 ◽

1987 ◽

Vol 26 (3) ◽

pp. 749-749 ◽

Cited By ~ 5

Author(s):

Athel Hockey ◽

Geoff Byrne ◽

Alex Cohen ◽

James F. Reynolds

Keyword(s):

Precocious Puberty ◽

Male Offspring ◽

Prader Willi Syndrome ◽

Mother And Daughter

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Central precocious puberty and growth hormone deficiency in a boy with Prader-Willi syndrome

European Journal of Pediatrics ◽

10.1007/s00431-008-0679-0 ◽

2008 ◽

Vol 167 (12) ◽

pp. 1455-1458 ◽

Cited By ~ 17

Author(s):

Antonino Crinò ◽

Girolamo Di Giorgio ◽

Riccardo Schiaffini ◽

Alessandra Fierabracci ◽

Sabrina Spera ◽

...

Keyword(s):

Growth Hormone ◽

Growth Hormone Deficiency ◽

Precocious Puberty ◽

Central Precocious Puberty ◽

Hormone Deficiency ◽

Prader Willi Syndrome

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Heterozygous Deletions in MKRN3 Cause Central Precocious Puberty Without Prader-Willi Syndrome

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa331 ◽

2020 ◽

Vol 105 (8) ◽

pp. 2732-2739

Author(s):

Brooke N Meader ◽

Alessandro Albano ◽

Hilal Sekizkardes ◽

Angela Delaney

Keyword(s):

Precocious Puberty ◽

Copy Number ◽

Genetic Diagnosis ◽

Central Precocious Puberty ◽

Chromosomal Microarray ◽

Imprinted Genes ◽

Prader Willi Syndrome ◽

Loss Of Function ◽

Gene Deletions ◽

Pubertal Onset

Abstract Context Loss-of-function mutations in the imprinted genes MKRN3 and DLK1 cause central precocious puberty (CPP) but whole gene deletions have not been reported. Larger deletions of the chromosome 15q11-13 imprinted locus, including MKRN3, cause Prader-Willi syndrome (PWS). CPP has been reported in PWS but is not common, and the role of MKRN3 in PWS has not been fully elucidated. Objective To identify copy number variants in puberty-related, imprinted genes to determine their role in CPP. Methods Probands with idiopathic CPP had chromosomal microarray (CMA) and targeted deletion/duplication testing for MKRN3 and DLK1. Results Sixteen female probands without MKRN3 or DLK1 variants identified by Sanger sequencing were studied. Whole gene deletions of MKRN3 were identified in 2 subjects (13%): a complete deletion of MKRN3 in Patient A (pubertal onset at 7 years) and a larger deletion involving MAGEL2, MKRN3, and NDN in Patient B (pubertal onset 5.5 years). Both were paternally inherited. Patient B had no typical features of PWS, other than obesity, which was also present in her unaffected family. Conclusions We identified 2 cases of whole gene deletions of MKRN3 causing isolated CPP without PWS. This is the first report of complete deletions of MKRN3 in patients with CPP, emphasizing the importance of including copy number variant analysis for MKRN3 mutation testing when a genetic diagnosis is suspected. We speculate that there is a critical region of the PWS locus beyond MKRN3, MAGEL2, and NDN that is responsible for the PWS phenotype.

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