Pre- and postnatal phenotype of 6p25 deletions involving the FOXC1 gene.

FOXC1 deletion, duplication, and mutations are associated with Axenfeld-Rieger anomaly, and Dandy-Walker malformation spectrum. We describe the clinical history, physical findings, and available brain imaging studies in three fetuses, two children, and one adult with 6p25 deletions encompassing FOXC1. Various combinations of ocular and cerebellar malformations were found. In all three fetuses, necropsy including detailed microscopic assessments of the eyes and brains showed ocular anterior segment dysgenesis suggestive of Axenfeld-Rieger anomaly. Five 6p25 deletions were terminal, including two derived from inherited reciprocal translocations; the remaining 6p25 deletion was interstitial. The size and breakpoints of these deletions were characterized using comparative genomic hybridization arrays. All six deletions included FOXC1. Our data confirm that FOXC1 haploinsufficiency plays a major role in the phenotype of patients with 6p25 deletions. Histopathological features of Axenfeld-Rieger anomaly were clearly identifiable before the beginning of the third-trimester of gestation.

Ultrasound assessment of the prognosis in triplet pregnancies.

OBJECTIVE: To assess the diagnostic accuracy and show the prognostic influence of different ultrasonographic criteria in triplet pregnancies(TP). DESIGN: Retrospective study. SETTING: Tertiary care center in France. POPULATION: Fifty-one consecutive TP in which at least one of the children, live- or stillborn, weighed 500 g or more, and with a gestation period of at least 22 weeks. METHODS: Chorionicity, abnormal umbilical artery Doppler waveforms, intrauterine weight (IUW) <10th centile and prenatal diagnosis of fetal anomaly were studied simultaneously as prognostic criteria. Chorionicity was confirmed at birth by placental pathology. MAIN OUTCOME MEASURES: Diagnosis of chorionicity/amnionicity and IUW <10th centile. Neonatal intensive care unit admission, occurrence of respiratory distress syndrome and perinatal mortality. RESULTS: Prenatal misclassification of chorionicity/amnionicity after postnatal perinatal pathology review was 12%. The positive predictive value of IUW <10th centile diagnosis was 44% for the prediction of birthweight <10th centile. Prenatal diagnosis of mono- or dichorionic placentation was associated with increased neonatal morbidity in comparison with that of trichorionic triplets. Perinatal mortality was significantly increased where mono- or dichorionic placentation was diagnosed prenatally (OR: 4.2; CI: 1.04-17), IUW <10th centile (OR: 10; CI: 2.4-41), with raised odds for abnormal umbilical Doppler measurements (OR: 9.7; CI: 2-47) and fetal anomaly (OR: 6.4; CI: 1.4-28.9). CONCLUSION: Early prenatal diagnosis of chorionicity is of major importance in triplet pregnancy. Experienced sonographers must quickly evaluate any uncertain diagnosis. In cases of unknown chorionicity, other ultrasonographic criteria can highlight high-risk triplet pregnancy, but at a later stage.

Zygosity and chorionicity in triplet pregnancies: new data.

BACKGROUND: In studies of twin and triplet pregnancies, molecular genetic techniques have rarely been used to confirm zygosity yet this is the most accurate approach. The aim of this study was to present the cross-distribution of chorionicity and zygosity in triplet pregnancies as a function of their mode of conception using such techniques. Rates of monozygosity were studied simultaneously. METHODS: Forty-nine consecutive sets of triplets were observed in the study, including 18 sets of spontaneously conceived (SC) triplet pregnancies and 31 sets resulting from assisted reproduction technologies (ARTs). Zygosity was determined through PCR-amplified microsatellite analysis. Chorionicity was determined by placental analysis in our department of fetopathology. Sets of triplets were considered as twin pairs in order to determine the rate of monozygosity. RESULTS: For SC triplet pregnancies, the rate of monozygotic (MZ) twin pairs was 48%; 30% of dichorionic (DC) triplet pregnancies were MZ and 70% dizygotic (DZ); 20% of trichorionic (TC) triplet pregnancies were DZ and 80% trizygotic (TZ). For triplet pregnancies conceived using ART, the rate of MZ twin pairs was 6.5%; 100% of DC triplet pregnancies were DZ; 4% of TC triplet pregnancies were DZ and 96% TZ. CONCLUSIONS: This study is the first report to present the cross-distribution of chorionicity and zygosity in triplet pregnancies as a function of their mode of conception. In triplet pregnancies conceived using ART, DC triplets are always DZ, and TC triplets are almost always TZ.

Zygosity and chorionicity in the prognosis of triplet pregnancies: contribution of microsatellites.

We assess the prognostic values of zygosity and chorionicity in triplet pregnancies (TP) with the assistance of microsatellites analysis. 53 consecutive TP whose prenatal care and delivery occurred in our maternity hospital were included in this prospective study. Zygosity of all sets of triplets (alive or stillbirth, after 22 weeks of gestation) was determined by PCR-amplified microsatellites markers analysis. Chorionicity was determined by placental analysis in our fetopathology referral department and validated by molecular analysis of zygosity. Placental conformations, obstetrical and neonatal outcomes of TP were studied according to their zygosity and chorionicity. Monozygotic and to a greater extent, dizygotic TP were associated with an increase in placental ischemic injuries, velamentous cord insertions, twin-twin transfusion syndromes, fetal anomalies, and perinatal mortality when compared with the trizygotic TP (p < 0.05). Monochorionic and more significantly, dichorionic TP presented with the same increases as trichorionic TP (p < 0.05). Thus chorionicity easily determined by ultrasound evaluation during the first trimester of the pregnancy must remain the main prognosis criterion in TP. Taking into account the rare indications of prenatal diagnosis of zygosity, it became apparent that chorionicity has a greater impact than zygosity when distinguishing high-risk groups of TP.

Humero-radial synostosis, microcephaly, short corpus callosum, and abnormal genitalia in sibs.

We report on two male sib fetuses with humero-radial synostosis and thumb hypoplasia, microcephaly with simplified gyral pattern, short corpus callosum and ambiguous genitalia. The main clinical, anatomopathological and imaging findings are presented and compared with previous cases of humero-radial synostosis as a prominent manifestation and with the X-linked lissencephaly with ambiguous genitalia syndrome (X-LAG). To our knowledge, this combination of anomalies has never been described before, and we propose that this disorder comprises a new humero-radial synostosis syndrome with an autosomal recessive or X-linked pattern of inheritance.