Can a mother's polycystic ovary syndrome (PCOS)-related symptoms be used to predict the future clinical profile of PCOS in her adolescent daughter? A pilot study.

OBJECTIVE: The aim of the study was to establish whether a mother's polycystic ovary syndrome (PCOS) symptoms can predict her daughter's future PCOS clinical profile. METHODS: This was a cross-sectional study of 57 adolescents who attended a paediatric gynaecology clinic between 2017 and 2019 and had an established diagnosis of PCOS according to the 2018 criteria of the European Society of Human Reproduction and Embryology. A clinical examination and pelvic ultrasound were performed and the level of total testosterone was measured. A structured questionnaire concerning PCOS symptoms was completed by the girls' mothers. RESULTS: It was found that 51% of girls with PCOS and 44% of their mothers had an elevated body mass index (BMI), and 35% of girls had an increased waist-hip ratio (>0.85). The mother's BMI significantly predicted her daughter's BMI and waist-hip ratio. It was reported that 40% of mothers had experienced menstrual irregularities, 50% hirsutism and 67% acne, and 12% had a confirmed diagnosis of PCOS. CONCLUSION: Our study population had several markers of poor metabolic health (increased BMI and waist-hip ratio) that were passed down from mother to daughter. No direct link was found between a mother's PCOS symptoms and those of her adolescent daughter. In order to establish definitive links between the symptoms of a mother and those of her daughter, a more comprehensive study should be conducted using a larger study sample. Additionally, a follow-up assessment of our studied adolescents would be appropriate to evaluate the progress of their symptoms.

The association of FMR1 gene (CGG)n variation with idiopathic female infertility.

INTRODUCTION: The FMR1 gene plays an important role in brain development and in the regulation of ovarian function. The FMR1 gene contains CGG repeat variation and the expansion of the repeats is associated with various phenotypes e.g. fragile X syndrome, premature ovarian failure, etc. Repeats ranging < 55 CGG are considered normal, however recent studies suggest that high-normal (35-54 CGG) and low-normal (< 26 CGG) alleles may also have an impact on female reproductive function. MATERIAL AND METHODS: We have performed a case-control study to assess the impact of FMR1 gene CGG repeats on female infertility. The study comprised 161 women with primary and secondary idiopathic infertility and 12 females with diminished ovarian reserve. The control group consisted of 129 healthy women with children. The FMR1 gene trinucleotide CGG repeat variation was detected using a triplet repeat primed polymerase chain reaction with capillary electrophoresis. RESULTS: The analysis of CGG repeats revealed that high-normal alleles are statistically significantly more common in the secondary infertility group than in controls (12% vs. 4.3%, p = 0.03, OR = 3.1, 95% CI: 1.1-8.3). The distribution of high-normal alleles and genotypes did not differ between patients with primary infertility and controls (p > 0.05). In addition, the analysis of low-normal allele and genotype frequencies did not present a difference between primary, secondary infertility and the control group (p > 0.05). CONCLUSIONS: In our study, the FMR1 gene high-normal alleles were associated with secondary infertility. However, to address the controversies related to the role of FMR1 genes in the development of diminished ovarian reserve, further studies on the subject are required.

The Fetal Phenotype of Noonan Syndrome Caused by Severe, Cancer-Related PTPN11 Variants.

BACKGROUND The nuchal translucency measurement is the major focus of an early fetal ultrasound scan, with the goal to identify various inherited conditions, such as chromosomal aberrations and others. The diagnostic strategy for fetuses with increased nuchal translucency and normal karyotype is not clearly defined and may vary between countries. CASE REPORT We describe 2 cases of Noonan syndrome diagnosed prenatally by ultrasound scanning and genetic testing. The prenatal ultrasound scans showed abnormal nuchal translucencies, cystic lymphangioma/cystic hygroma, and other findings. Both fetuses had normal karyotype; however, after additional analysis, pathogenic variants of the PTPN11 gene (encoding SH2 domain-containing protein tyrosine phosphatase) were found, previously frequently described as somatic variants in hematological malignancies in postnatal life, but not previously described with severe prenatal phenotype of Noonan syndrome. CONCLUSIONS Our case reports confirm the hypothesis that severe, cancer related PTPN11 variants cause severe Noonan syndrome prenatal phenotype, when inherited in the germline.Analysis of pathogenic variants associated with Noonan syndrome should be included in the prenatal diagnostics for fetuses with increased nuchal translucency and normal karyotype.