Eyal Mazaki

Loss of function of PCDH12 underlies recessive microcephaly mimicking intrauterine infection

Objective: To identify the genetic basis of a recessive syndrome characterized by prenatal hyperechogenic brain foci, congenital microcephaly, hypothalamic midbrain dysplasia, epilepsy, and profound global developmental disability. Methods: Identification of the responsible gene by whole exome sequencing and homozygosity mapping. Results: Ten patients from 4 consanguineous Palestinian families manifested in utero with hyperechogenic brain foci, microcephaly, and intrauterine growth retardation. Postnatally, patients had progressive severe microcephaly, neonatal seizures, and virtually no developmental milestones. Brain imaging revealed dysplastic elongated masses in the midbrain–hypothalamus–optic tract area. Whole exome sequencing of one affected child revealed only PCDH12 c.2515C>T, p.R839X, to be homozygous in the proband and to cosegregate with the condition in her family. The allele frequency of PCDH12 p.R839X is <0.00001 worldwide. Genotyping PCDH12 p.R839X in 3 other families with affected children yielded perfect cosegregation with the phenotype (probability by chance is 2.0 × 10−12). Homozygosity mapping revealed that PCDH12 p.R839X lies in the largest homozygous region (11.7 MB) shared by all affected patients. The mutation reduces transcript expression by 84% (p < 2.4 × 10−13). PCDH12 is a vascular endothelial protocadherin that promotes cellular adhesion. Endothelial adhesion disruptions due to mutations in OCLN or JAM3 also cause congenital microcephaly, intracranial calcifications, and profound psychomotor disability. Conclusions: Loss of function of PCDH12 leads to recessive congenital microcephaly with profound developmental disability. The phenotype resembles Aicardi-Goutières syndrome and in utero infections. In cases with similar manifestations but no evidence of infection, our results suggest consideration of an additional, albeit rare, cause of congenital microcephaly.

Omega-shaped variant of the umbilical artery: prenatal diagnosis and outcome.

The purpose of this series was to report on the observation of an anomalous course of the umbilical artery. Ten cases in a 25‐month period are reported. An omega‐shaped variant, coined the “omega sign,” of one of two umbilical arteries or of a single umbilical artery was observed. In 2 cases, there were two umbilical arteries, one of them with the anomalous vessel. In 8 cases, the vessel was a single umbilical artery. In 1 case with a single umbilical artery and pericardial effusion, aneuploidy was found on amniocentesis. A second case was associated with multiple anomalies. A third case was associated with hypoplastic left heart syndrome. Seven cases with the omega sign as an isolated finding, with or without a single umbilical artery, had favorable outcomes. An omega‐shaped variant of the umbilical artery is likely to be more common in cases of a single umbilical artery than in cases with two umbilical arteries. It is probably a normal variant when unassociated with additional sonographically detectable structural anomalies.

OP33.05: The prenatal diagnosis of isolated varix of the fetal intra‐abdominal umbilical vein (VFIUV): iatrogenic prematurity is not obligatory

Amniocentesis was performed, and we confirmed the presence of meconium in 3 of them. The fetus with the amniotic fluid clear amniocentesis showed intestinal obstruction with reflux of stomach contents due to the narrow opening of the abdominal wall defect. There was no rupture of the bowel. There were no cases of bowel perforation in the other 24 fetuses. Conclusions: The presence of debris in the amniotic fluid and in the gastric contents, associated with the classic signs of bowel distress, may be an important tool to detect the presence of bowel perforation.

First trimester expression of anorectal malformation: Case report and review of the literature

A 26‐years‐old woman, underwent an ultrasound examination at 13.4 weeks. A cystic structure was identified in the right lower abdomen. Gradually, the cystic mass was replaced by echogenic content and eventually attained the appearance of hyperechoic bowel. At 21.2 weeks, the anal sphincter could not be demonstrated which was consistent with the diagnosis of isolated anal agenesis. Amniocentesis revealed 46XY karyotype with normal comparative genomic hybridization. After termination of pregnancy at 23 weeks, an autopsy revealed an isolated high type anorectal malformation (ARM) without fistula. We reviewed all 14 cases reported in the literature of first trimester sonographic expression of ARM.

P02.18: Early second‐trimester amniotic shelf—a common, transient, benign finding on early second‐trimester sonography

Objective: To assess the predictive value of an elongated stomach in the fetal abdomen on a longitudinal scan as an early sign of congenital diaphragmatic hernia. Methods: Serial sonograms were performed in 2 cases with thirdtrimester prenatal diagnosis of diaphragmatic hernia and postnatal follow-up was obtained. Results: We retrospectively reviewed our cases of congenital diaphragmatic hernia. In 2 of them, despite final diagnosis was made in the third trimester, suspicion was raised at midtrimester based upon the ultrasound finding of dislocation of the stomach in the fetal abdomen, which appeared with peculiar elongated and narrow morphology on longitudinal scan. Conclusions: Prenatal diagnosis of diaphragmatic hernia can be made since midtrimester, although it is frequently achieved in late gestation only. We herein suggest the potential for a peculiar sonographic feature of the fetal stomach at midtrimester as a highly predictive sign for such malformation.