Familial transmission of chromoanagenesis leads to unpredictable unbalanced rearrangements through meiotic recombination.

Chromoanagenesis is a cellular mechanism that leads to complex chromosomal rearrangements (CCR) during a single catastrophic event. It may result in loss and/or gain of genetic material and may be responsible for various phenotypes. These rearrangements are usually sporadic. However, some familial cases have been reported. Here, we studied six families in whom an asymptomatic or paucisymptomatic parent transmitted a CCR to its offspring in an unbalanced manner. The rearrangements were characterized by karyotyping, fluorescent in situ hybridization, chromosomal microarray (CMA) and/or whole genome sequencing (WGS) in the carrier parents and offspring. We then hypothesized meiosis-pairing figures between normal and abnormal parental chromosomes that may have led to the formation of new unbalanced rearrangements through meiotic recombination. Our work indicates that chromoanagenesis might be associated with a normal phenotype and normal fertility, even in males, and that WGS may be the only way to identify these events when there is no imbalance. Subsequently, the CCR can be transmitted to the next generation in an unbalanced and unpredictable manner following meiotic recombination. Thereby, prenatal diagnosis using CMA should be proposed to these families to detect any pathogenic imbalances in the offspring.

Prenatal Diagnosis of Trisomy 2p due to Terminal 2p Duplication including Interstitial Telomeric Sequences.

We report on a prenatally diagnosed unusual case of inverted terminal duplication of the short arm of chromosome 2, leading to interstitial telomeric sequences (ITSs) and partial trisomy 2p. To our knowledge, there are only 4 further cases of pure partial trisomy 2p reported prenatally. Here, the mother was referred at 22 weeks of gestation for isolated fetal congenital heart malformation at ultrasound. The karyotype of amniotic fluid cells displayed a large duplication of the short arm of chromosome 2 that was further investigated by array-CGH, which detected a 1-copy gain of 43.75 Mb in chromosome 2 at 2p21p25.3. FISH confirmed the presence of an inverted duplication in the short arm of chromosome 2 involving the region 2p21pter and revealed the presence of ITSs at the breakpoint in chromosome 2p21. This report contributes to the prenatal description of the syndrome. We also discuss the possible mechanisms leading to this duplication and the formation of ITSs which are rarely described in constitutional rearrangements.

A risk score for the management of pregnant women with increased risk of venous thromboembolism: a multicentre prospective study.

Patients with thrombophilia and/or a history of venous thromboembolism (VTE) exhibit a high risk of thrombosis during pregnancy. The present multicentre study prospectively assessed a prophylaxis strategy, based on a risk score, in pregnancies with increased risk of VTE. Among 286 patients included in the study, 183 had a personal history of VTE (63.98%) and 191 patients (66.8%) had a thrombophilia marker. Eighty nine (46.6%) thrombophilic women had a personal history of VTE. Patients were assigned to one of three prophylaxis strategies according to the risk scoring system. In postpartum, all patients received low molecular weight heparin (LMWH) prophylaxis for at least 6 weeks. In antepartum, LMWH prophylaxis was prescribed to 61.8% of patients with high risk of VTE. Among them, 37.7% were treated in the third trimester only and 24.1% were treated throughout pregnancy. In this cohort, one antepartum-related VTE (0.35%) and two postpartum-related VTE (0.7%) occurred. No case of pulmonary embolism was observed during the study period. The rate of serious bleeding was 0.35%. There was no evidence of heparin-induced thrombocytopenia or osteoporosis. The use of a risk score may provide a rational decision process to implement safe and effective antepartum thromboprophylaxis in pregnant women at high risk of VTE.

Focal sonographic periventricular pattern associated with mild ventriculomegaly in foetal cytomegalic infection revealing cytomegalic encephalitis in the third trimester of pregnancy.

OBJECTIVES: To report focal sonographic periventricular pattern related to residual germinal matrix lesions in foetal cytomegalic infection in association with mild ventriculomegaly seen during the third trimester of pregnancy correlating with neuropathological findings of encephalitis. METHODS: We reviewed prenatal cerebral sonographic examination performed in three patients, during the third trimester of pregnancy, looking for either late 'isolated' ventriculomegaly (n = 2) or sonographic follow-up of cerebral structures following a known primary CMV infection in the early stage of pregnancy (n = 1). In cases of isolated ventriculomegaly, serological examination identified prenatal CMV infection. Magnetic resonance imaging (MRI) was performed in all cases. Imaging findings were compared with those following neuropathological examination. RESULTS: In all cases, ultrasound examination revealed an abnormal focal symmetrical bilateral periventricular pattern on the mid-lateral border of the lateral ventricles, including a mainly hyperechogenic lesion containing a few microcysts (case 1), a mixture of echogenic tissue and cysts (case 2) and mainly cystic areas (case 3). No alteration of cephalic biometry was noted. Neuropathological examination correlated these abnormal areas with lesions of the residual germinal matrix including inflammation and necrosis, but revealed also an extensive inflammatory process of the whole foetal brain. CONCLUSIONS: This focal sonographic periventricular pattern associated with mild ventriculomegaly without any abnormalities of the cerebral and cerebellar organogenesis nor cephalic biometry alteration in the third trimester of pregnancy should be considered as a marker of encephalitis following CMV infection of the foetal brain.