Associations between congenital heart defects and genetic and morphological anomalies. The importance of prenatal screening.

AIM: To study congenital heart defects (CHDs), evaluate their relation to extra-cardiac pathologies, and assess the significance of prenatal diagnostics for heart diseases. METHODS: Data from 1999-2017 were analyzed for the incidence of significant CHDs in fetuses (prenatal ultrasound/echocardiography) and children, including, where applicable, autopsy data and genetic evaluation. RESULTS: Among 220,400 fetuses, 819 (3.7 cases per 1000) significant CHDs were observed. Of the total, 53% (435/819) of CHDs were diagnosed prenatally. The heart defect was an isolated impairment in 78% (640/819), associated with a genetic impairment in 16% (128/819), and with extra-cardiac malformations without genetic pathology in 6% (51/819). Chromosomal aberrations were diagnosed prenatally in 70% (90/128) of those affected and extra-cardiac conditions in 86% (44/51). The CHD and genetic pathology association was more frequent prenatally [21% (90/435) vs. postnatally: 10% (38/384; P<0.0001)], as was the association between CHD with other extra-cardiac pathology and a normal karyotype [prenatally: 10% (44/435) vs. postnatally: 2% (7/384; P<0.0001)]. CONCLUSION: Heart defects are most frequently isolated, with genetic and other extra-cardiac anomalies in about one third of cases, significantly linked to prenatal diagnostics.

High incidence of monozygotic twinning after assisted reproduction is related to genetic information, but not to assisted reproduction technology itself.

OBJECTIVE: To study the incidence of monozygotic twinning (MZT) in patients using in vitro fertilization, relative to their age, genetic background, ovarian function, and assisted reproductive techniques used. DESIGN: Analysis of a collected database. SETTING: Infertility treatment center. PATIENT(S): A total of 1,876 patients receiving infertility treatment between 2000 and 2012. Pregnancies with monozygotic twins (A: 23) were compared with deliveries of dizygotic twins (B: 423), singleton pregnancies (C: 880), and aborted pregnancies (D: 389). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): A genetic survey on multiple pregnancies in the extended family. Measures were micromanipulation technique, the length of embryo cultivation, type of cultivation media, basal follicle-stimulating hormone level, estradiol level on the day of human chorionic gonadotropin administration, number of oocytes, total consumption of gonadotropins, and consumption of gonadotropins needed for recovery of 1 oocyte. RESULT(S): No differences were found between the incidence of MZT in cycles that did vs. did not use micromanipulation techniques. In addition, the length of embryo cultivation or type of cultivation media used did not affect the results. Estradiol levels and implantation rates were significantly higher in group A. The incidence of MZT in families in group A was significantly higher than that in groups B and C. CONCLUSION(S): We propose that the high incidence of MZT in infertility-clinic patients is conditioned by hereditary factors, and good ovarian function only facilitates the expression. The resulting recommendation is that young women with a positive family history and good ovarian function undergo elective single-embryo transfer, and proper counseling is advisable.

Molecular and clinical characterization of two patients with Prader-Willi syndrome and atypical deletions of proximal chromosome 15q.

Prader-Willi syndrome (PWS) is caused by the disturbed expression of genes from the imprinted region of 15q11-q13, but the specific contributions of individual genes remain unknown. Most paternal PWS deletions are bracketed by recurrent breakpoints BP1 or BP2 and BP3. Atypical deletions are very rare. In the present work, we describe the molecular analysis of two patients with atypical deletions using microsatellite analysis, methylation-specific MLPA, and microarray CGH. A deletion of about 2 Mb in Patient 1 started at BP2 and ended in the middle of the typically deleted region within the UBE3A gene. The deletion in Patient 2 started 1.3 Mb distal from BP2 within the C15ORF2 gene, extended over 9.5 Mb, and ended within the AVEN gene in proximal 15q14. In Patient 1 both deletion breakpoints involved repetitive regions, which precluded cloning of the junction and pointed to non-allelic homologous recombination as a possible mechanism of this rearrangement. The breakpoints in Patient 2 were sequenced, and their structure suggested non-homologous end joining as the most likely cause of this deletion. The phenotype of both patients did not depart significantly from the typical clinical picture of PWS, although some symptoms in Patient 2 were also reminiscent of the phenotype of individuals with the recently described 15q13.3 microdeletion syndrome. Our findings support previous observations of relatively mild phenotypic effects resulting from deletions that extend distally from the PWS region and observations of the modest effects of different types of genetic defects on the spectrum and severity of symptoms in PWS.

Elejalde syndrome--a case report.

Elejalde syndrome (McKusick 200995), also known as acrocephalopolydactylous dysplasia, is a rare condition. We describe a sixth patient with this syndrome which is characterized by craniosynostosis and hyperproliferation of fibroblasts in many tissues including skin, liver, kidney, and pancreas. The cause of the syndrome is the homozygous state of an autosomal recessive mutation. We present a hypothesis that Elejalde syndrome might be associated with an inactivating FGFR gene mutation.