The genetics of recurrent hydatidiform moles: new insights and lessons from a comprehensive analysis of 113 patients.

Hydatidiform mole is an aberrant human pregnancy characterized by early embryonic arrest and excessive trophoblastic proliferation. Recurrent hydatidiform moles are defined by the occurrence of at least two hydatidiform moles in the same patient. Fifty to eighty percent of patients with recurrent hydatidiform moles have biallelic pathogenic variants in NLRP7 or KHDC3L. However, in the remaining patients, the genotypic types of the moles are unknown. We characterized 80 new hydatidiform mole tissues, 57 of which were from patients with no mutations in the known genes, and we reviewed the genotypes of a total of 123 molar tissues. We also reviewed mutation analysis in 113 patients with recurrent hydatidiform moles. While all hydatidiform moles from patients with biallelic NLRP7 or KHDC3L mutations are diploid biparental, we demonstrate that those from patients without mutations are highly heterogeneous and only a small minority of them are diploid biparental (8%). The other mechanisms that were found to recur in patients without mutations are diploid androgenetic monospermic (24%) and triploid dispermic (32%); the remaining hydatidiform moles were misdiagnosed as moles due to errors in the analyses and/or their unusual mechanisms. We compared three parameters of genetic susceptibility in patients with and without mutations and show that patients without mutations are mostly from non-familial cases, have fewer reproductive losses, and more live births. Our data demonstrate that patients with recurrent hydatidiform moles and no mutations in the known genes are, in general, different from those with mutations; they have a milder genetic susceptibility and/or a multifactorial etiology underlying their recurrent hydatidiform moles. Categorizing these patients according to the genotypic types of their recurrent hydatidiform moles may facilitate the identification of novel genes for this entity.

Two Consecutive Pregnancies with Simpson-Golabi-Behmel Syndrome Type 1: Case Report and Review of Published Prenatal Cases.

Fetal overgrowth and numerous congenital malformations can be detected in every trimester of pregnancy. New technologies in molecular testing, such as chromosomal microarray analysis and next-generation sequencing, continually demonstrate advantages for definitive diagnosis in fetal life. Simpson-Golabi-Behmel (SGB) syndrome is a rare but well-known overgrowth condition that is rarely diagnosed in the prenatal setting. We report 3 cases of SGB syndrome in 2 consecutive pregnancies. In our series, distinctive prenatal sonographic findings led to molecular diagnosis. Exome sequencing from fetal DNA revealed a hemizygous splice site variant in the GPC3 gene: NM_004484.3:c.1166+ 1G>T. The mother is a heterozygous carrier. We also provide an overview of the previously published 57 prenatal cases of SGB syndrome with prevalence estimation of the symptoms to aid prenatal differential diagnosis of fetal overgrowth syndromes.

Validity of self-reported height and weight for estimating prevalence of overweight among Estonian adolescents: the Health Behaviour in School-aged Children study.

BACKGROUND: Low to moderate agreement between self-reported and directly measured anthropometry is shown in studies for adults and children. However, this issue needs further evaluation during puberty, a period marked by several transitions. We examined the correspondence of BMI status based on self-reported versus measured anthropometric data among Estonian adolescents with a specific focus on gender and age differences. METHODS: Self-reported height and weight were determined in a national representative sample of Estonian schoolchildren collected within the framework of the HBSC (health behaviour of school-aged children) survey. Self-reported and directly measured height and weight were collected from 3379 students (1071 aged 11, 1133 aged 13 and 1175 aged 15 years). The standardized HBSC questionnaire was used for collecting self-reported data; direct anthropometric measures were taken after the HBSC questionnaires were completed. The accuracy of the self-reported values by age and gender groups were determined by comparing mean differences, Bland-Altman plots with limits of agreement, Kappa statistics, and by estimation of the sensitivity and positive predictive value for detecting overweight. RESULTS: Mean self-reported weight, height and body mass index (BMI) values were significantly lower than corresponding values obtained using direct measurements. Mean differences between self-reported and directly measured weight, height and BMI were largest among 11-year-olds and smallest among students aged 15 years. Underestimation of overweight prevalence (includes obese) showed a graded trend which decreased in older age groups; the difference was greater among girls than boys in all age groups. The mean underestimation of overweight prevalence based on self-reported anthropometry was 3.6 percentage points. The positive predictive value was 72.3 % for boys and 63.4 % for girls. CONCLUSION: A distinct age-related pattern in underestimation of weight, height and prevalence of overweight was found; the bias decreased with increasing age. The mean underestimation of overweight prevalence based on self-reports was small, 3.6 %. Self-reported height and weight remain the method of choice in large surveys for practical and logistical reasons.

Improvements in fitness reduce the risk of becoming overweight across puberty.

PURPOSE: Information about factors related to overweight development in early stages of life is needed for designing useful strategies to prevent overweight and related diseases. Longitudinal studies can contribute to this goal. The present study aimed to identify factors in childhood that determine the development of overweight/obesity in adolescence. METHODS: A prospective study in 598 normal-weight Estonian and Swedish children age 9.5 ± 0.4 yr from the European Youth Heart Study, who were followed during 6 yr, was conducted. Weight and height were measured at baseline and follow-up, and weight status was ascertained according to the international criteria for body mass index. Cardiorespiratory fitness (expressed as VO(2max) (mL·kg(-1)·min(-1))) was assessed by a maximal bike test. Parents reported their weight, height, and educational level. RESULTS: Being male (vs female) and Estonian (vs Swedish) was related to higher risk for incident overweight/obesity. Change in fitness was a stronger predictor of incident overweight/obesity than childhood fitness, parental overweight, or parental education. The risk of developing overweight/obesity was reduced 10% every 1 mL·kg(-1)·min(-1) of VO(2max) increase (odds ratio = 0.90 and 95% confidence interval = 0.84-0.95) after adjustment for a set of confounders including baseline body mass index and without differences by gender. CONCLUSIONS: Our results suggest that improvements in fitness from childhood to adolescence are associated with a lower risk of becoming overweight/obese in adolescence. The current findings highlight the importance of promoting fitness through physical exercise from early stages in life, as a promising strategy to fight against overweight and obesity. Gender and country differences observed in this study require social and political attention.

Aggregation of lipoprotein and inflammatory parameters in families with a history of premature myocardial infarction: the Tallinn myocardial infarction study.

BACKGROUND: The offspring of individuals with a history of premature myocardial infarction are at increased risk of premature coronary attacks. The aim of this study was to determine parent/offspring associations of coronary risk factors in families affected by premature myocardial infarction and to compare these to corresponding control families. METHODS: The cohort of cases consisted of 71 male survivors of myocardial infarction and their 128 descendants (aged 7-18 years). As control families, 85 randomly selected healthy males with their 66 descendants were investigated. Besides traditional risk factors, serum high sensitive C-reactive protein (hsCRP), apolipoprotein (apo) E phenotypes and lipoprotein(a) were analyzed. RESULTS: In the offspring of the patients, fibrinogen and atherogenic lipoprotein parameters were higher than in the corresponding controls, but hsCRP, lipoprotein(a) and anthropometric data did not differ between the groups. The adult-offspring positive correlations were detected in fibrinogen and in almost all measured lipoprotein fractions in the affected families; amongst the controls, the association was observed only for triglyceride levels. Multiple logistic regression analysis demonstrated independent association of offspring apoB, apoA-I and fibrinogen levels with a family history of premature myocardial infarction. CONCLUSIONS: The most informative predictors of future coronary attacks during childhood are apoB-100 and apoB/apoA-I ratio; serum hsCRP and lipoprotein(a) do not have predictive value in childhood.