Facial Dysmorphism With Multiple Malformations

In 2 female fetuses born of first-cousin Pakistani parents, Thakker and Donnai (1991) described a syndrome of facial dysmorphism and multiple anomalies. The first fetus was delivered after therapeutic termination at 26 weeks' gestation for multiple structural abnormalities identified on ultrasound scanning. The palpebral fissures were long, downward slanting and widely separated; the nose was short and bulbous tipped; the mouth was small with downturned corners; and the neck was short and webbed. Autopsy showed dilatation of the ventricular system, Klippel-Feil anomaly, transposition of the great vessels with ventricular septal defect, and very short esophagus with intrathoracic stomach, small intestine, spleen, and pancreas. The umbilical cord had 4 vessels. The second affected sib was liveborn at 36 weeks' gestation. She had identical facial features, anal atresia associated with rectovaginal fistula, hemivertebra, agenesis of the corpus callosum, and tetralogy of Fallot. She died at age 53 days. Necropsy limited to a muscle biopsy showed uniform muscle atrophy compatible with a neurogenic origin.