PMC5224777_01
Comparison between the proband and her healthy brother. A-B, facial appearance of the MWS patient and her brother. The patient has large and deep-set eyes, telecanthus, round nasal tip with a prominent columella (beaked nose), short philtrum, frontal bossing, and micrognathia. C-D, a heterozygous mutation of c.904 C>T was detected by target gene NGS and verified by Sanger sequencing in the patient. Amniocentesis was performed at 19 + 1 weeks for her brother and genetic testing demonstrated him to be wild type. E-F, representation of the newborn echocardiogram examination on the patient and her brother. The patient has multiple muscular ventricular septal defect (VSD), multiple ostium secundum atrial septal defect (ASD), persistent ductus arteriosus (PDA), and pulmonary stenosis (PS).
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On primary examination, no specific facial characteristics were found prompting to any known syndromes, except for the profound microcephaly with a head circumference of 31 cm (<1st centile) (Fig. 1A). A nonsense mutation in ZEB2, denoted as p.Arg302Stop at the protein level (Fig. 1C), appeared as the strongest candidate. Amniocentesis was performed at 19 + 1 weeks for genetic testing which revealed a normal 46, XY karyotype, and wild-type status of the p.Arg302 (Fig. 1D). The mother gave birth to a healthy boy (Fig. 1B) in March 2016 with a birthweight of 3870 g (between the 75th and 85th centile), length of 52 cm (between the 85th and 95th centile) and head circumference of 35 cm (between the 50th and 75th centile). The baby passed meconium at 3 h after birth, and the newborn echocardiogram examination revealed no obvious heart defects (Fig. 1F).
Prenatal ultrasound examinations of the proband's sibling. (A) Axial plane showed the cavum septi pellucid (CSP) in prenatal scan at 30 weeks of gestation. (B) Axial plane showed the lateral ventricle (LV) in prenatal scan at 21 weeks of gestation. (C) Fetal echocardiography at 21 weeks of gestation showed normal four-chamber view. (D) Normal male genitalia showed in scan at 30 weeks of gestation.
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Follow-up prenatal scans at 30 and 36 weeks presented no abnormal findings associated with MWS (Fig. 2).