Clinical, Biological and Genetic Analysis of Prepubertal Isolated Ovarian Cyst in 11 Girls

Raja Brauner,Pascal Philibert,Christine Trivin,Hélène Sarda-Thibault,Micheline Misrahi,Marie Goulet,Ken Mcelreavey,Charles Sultan,Sébastien Rouget,Anu Bashamboo,Syed A Aziz

doi:10.1371/journal.pone.0011282

Abstract

BackgroundThe cause of isolated gonadotropin-independent precocious puberty (PP) with an ovarian cyst is unknown in the majority of cases. Here, we describe 11 new cases of peripheral PP and, based on phenotypes observed in mouse models, we tested the hypothesis that mutations in the GNAS1, NR5A1, LHCGR, FSHR, NR5A1, StAR, DMRT4 and NOBOX may be associated with this phenotype.Methodology/Principal Findings11 girls with gonadotropin-independent PP were included in this study. Three girls were seen for a history of prenatal ovarian cyst, 6 girls for breast development, and 2 girls for vaginal bleeding. With one exception, all girls were seen before 8 years of age. In 8 cases, an ovarian cyst was detected, and in one case, suspected. One other case has polycystic ovaries, and the remaining case was referred for vaginal bleeding. Four patients had a familial history of ovarian anomalies and/or infertility. Mutations in the coding sequences of the candidate genes GNAS1, NR5A1, LHCGR, FSHR, NR5A1, StAR, DMRT4 and NOBOX were not observed.Conclusions/SignificanceOvarian PP shows markedly different clinical features from central PP. Our data suggest that mutations in the GNAS1, NR5A1, LHCGR, FSHR StAR, DMRT4 and NOBOX genes are not responsible for ovarian PP. Further research, including the identification of familial cases, is needed to understand the etiology of ovarian PP.

Highlights

Precocious puberty (PP) in girls is defined by the development of sexual characters and increased growth rate before 8 years-of-age [1]
These data suggest a strong genetic contribution to the phenotype in each case, but no mutations in the GNAS1, LHCGR, FSHR, Steroidogenic Acute Regulatory (StAR), NR5A1, DMRT4 and NOBOX were found, including DNA extracted from the ovarian cyst tissue in case 9
Clinical and biological presentation The presentation of the 8 postnatally diagnosed cases differs from the typical presentation of central precocious puberty (PP)

Summary

Introduction

Precocious puberty (PP) in girls is defined by the development of sexual characters (development of breasts, pubic and menstrual bleeding) and increased growth rate before 8 years-of-age [1]. There are two major categories of precocious puberty: true or central PP and pseudo or peripheral PP. True and peripheral isosexual PP can be distinguished by measuring basal, and gonadotropin releasing hormone (GnRH)-stimulated luteinising hormone (LH) and follicle stimulating hormone (FSH) peaks concentrations. These concentrations increase in true PP [3] while they are low and do not increase in peripheral PP. The cause of isolated gonadotropin-independent precocious puberty (PP) with an ovarian cyst is unknown in the majority of cases. We describe 11 new cases of peripheral PP and, based on phenotypes observed in mouse models, we tested the hypothesis that mutations in the GNAS1, NR5A1, LHCGR, FSHR, NR5A1, StAR, DMRT4 and NOBOX may be associated with this phenotype

Methods

Results

Conclusion