Peculiarities of Precocious Puberty in Boys and Girls With McCune-Albright Syndrome

Abstract

McCune-Albright Syndrome (MAS; OMIM # 174800) is a rare, sporadic disease caused by a post-zygotic, activating mutation in the guanine-nucleotide binding protein α-subunit (GNAS1) gene. MAS is characterized by the clinical triad of polyostotic fibrous dysplasia of bone, café-au-lait skin pigmentation and peripheral precocious puberty. However, clinical presentation is highly variable depending on mosaic tissue distribution of mutant-bearing cells. Precocious puberty is the most common endocrine manifestation of MAS and is often the presenting, and sometimes the only, clinical sign of MAS. Due to the very low prevalence of MAS, data on course of precocious puberty, effectiveness of treatments and gonadal function during post-pubertal period are lacking. Our knowledge on this issue derives essentially from case reports and small cohorts of patients. The aim of this review is to report all available literature data on clinical aspects, therapeutic management and outcomes of precocious puberty in children with MAS. A systematic research was carried out through MEDLINE via PubMed, EMBASE, Web of Science, Semantic Scholar, Cochrane Library.

Café au Lait Macules and Associated Genetic Syndromes

“…The presentation of precocious puberty in females is highly variable and unpredictable. Girls may present with gonadotropin-independent precocious puberty caused by recurrent estrogen-producing ovarian cysts, vaginal bleeding as young 2 years of age, breast tissue development, and enhanced growth and bone age (Boyce et al, 2018;Corica, Aversa, Pepe, De Luca, & Wasniewska, 2018). Biochemical findings include high estradiol levels and diminished gonadotropins.…”

“…Although rare in males, signs of precocious puberty result from autonomous testosterone production and include macroorchidism with or without signs of sexual precocity. Testicular lesions in the presence or absence of gonadotropin-independent precocious puberty may occur (Corica et al, 2018).…”

A rare case of McCune Albright syndrome

“…Its prevalence is estimated to range between 1/100 000 and 1/1 000 000. 1,2 This mutation of GNAS gene is a post-zygotic event, which leads to a mosaic presentation of the gene. This explains the broad clinical spectrum of this disease.…”

“…1 Precocious puberty is the most common manifestation and if often the presenting, and only clinical sign of MAS. 2 It is defined as the onset of the evidence of puberty before the age of 8 years. This includes the presence of either of the following: development of breasts (thelarche), appearance of pubic hair (pubarche), and beginning of menstruation (menarche).…”

Phenotypic testicular abnormalities and pubertal development in boys with McCune-Albright syndrome

“…By contrast, the two testicular cell populations (Leydig and Sertoli cells) play a different physiologic role in the hormone biosynthesis. Therefore, whereas in MAS girls the activating mutation in the GNAS gene is almost always followed by a precocious increase of estrogen secretion, in boys an early androgen secretion may be observed only when this mutation involves Leydig cells, but not in the cases where are the Sertoli cells to carry the mutation [ 12 ].…”