The WNT-signaling pathway plays a major role during mammalian embryogenesis. We report a novel autosomal-recessive syndrome that consists of female to male sex reversal and renal, adrenal, and lung dysgenesis and is associated with additional developmental defects. Using a candidate-gene approach, we identified a disease-causing homozygous missense mutation in the human WNT4 gene. The mutation was found to result in markedly reduced WNT4 mRNA levels in vivo and in vitro and to downregulate WNT4-dependent inhibition of beta-catenin degradation. Taken together with previous observations in animal models, the present data attribute a pivotal role to WNT4 signaling during organogenesis in humans.

Objective: Hemivertebra is a rare congenital spinal anomaly where only one side of the vertebral body develops, resulting in deformation of the spine, such as scoliosis, lordosis, or kyphosis. We aimed to determine the incidence and clinical characteristics of hemivertebra. Patients and Methods: We present three fetuses with a prenatal ultrasonographic diagnosis of hemivertebra at 15–22 weeks’ gestation, and we determine the incidence and clinical characteristics of hemivertebra among 78,500 live-born infants at a tertiary medical center in Israel. Results: There were 26 cases of hemivertebra (0.33/1,000 live-born infants): male/female ratio 1/1, Jewish/Arab ratio 10/16, and ratio of single/multiple type of hemivertebrae 17/9. Twenty-three out of 26 infants (88.5%) with hemivertebra had additional congenital anomalies (cranial, cardiac, renal, intestinal, and skeletal). Conclusions: Hemivertebra is not an infrequent finding in fetuses and live-born infants. Comprehensive ultrasonographic screening of the fetus allows early prenatal diagnosis of hemivertebra, and provides parents with helpful information for their decision regarding the fate of pregnancy.

Parental decisions concerning the continuation of pregnancy following prenatal detection of abnormal chromosomes were evaluated for 80 patients whose diagnosis and prenatal counselling were performed in our centre. Twenty-two anomalies were diagnosed by chorionic villus sampling (CVS) and 58 by amniocentesis. The severity of the chromosome anomaly and associated ultrasound findings in the first vs. second trimester were correlated with patients' decisions. No difference was found in the likelihood of parental decisions to interrupt or continue a pregnancy between CVS and amniocentesis for either the 'severe' or the 'questionable' group of chromosome anomalies. Ninety-three per cent of patients with severe prognosis and 27 per cent with questionable prognosis opted for pregnancy termination (p less than 0.0001). The association of ultrasound anomalies and termination was highly significant (p less than 0.001). The severity of the chromosome anomaly, and, to a lesser extent, the visualization of anomalies on ultrasound were the major determinants of parental decisions to terminate the pregnancy. The diagnosis of an anomaly in the first trimester was no more likely ito lead to a termination of pregnancy than in the second trimester.