CHARGE syndrome in a fetus with a large paraesophageal hernia presenting prenatally as esophageal atresia

Abstract

We report on the case of a 28-year-old primigravida with polyhydramnios and a fetus with mild bilateral ventriculomegaly, a large cyst in the right lateral ventricle, a fluid-filled structure posterior to a normal heart (Figure 1) and a missing stomach. After delivery, bilateral retinal coloboma, micrognathia, bilateral external ear abnormalities and a submucous cleft palate with excessive salivation were noted. Esophago- and tracheoscopy excluded esophageal atresia and tracheoesophageal fistula, but X-ray of the chest and a barium swallow examination revealed a large left-sided paraesophageal hernia of the stomach (Figure 2). Neonatal echocardiography showed a persistent foramen ovale and, on magnetic resonance imaging, an aberrant right subclavian artery and left-sided choanal atresia could be seen. Other notable findings were dysphonia and hypocalcemia. A diagnosis of CHARGE syndrome was established based on the presence of four major features of the syndrome (bilateral coloboma, choanal atresia, swallowing difficulties and external ear abnormalities)1. CHARGE is a rare congenital anomaly syndrome, with ocular coloboma, congenital heart defects, choanal atresia, retardation of growth and development, genital hypoplasia and ear anomalies associated with deafness. The syndrome was first described in 1979 by B.D. Hall, as referenced by Blake and Prasad1. Its incidence is 0.1–1.2 per 10 000 deliveries1. In most cases, de novo truncating mutations in the gene encoding the chromodomain helicase DNA binding protein 7 (CHD7), located on chromosome 8q12, cause the syndrome2. Mutations in the CHD7 gene have been demonstrated in 42–64% of cases3. The clinical diagnosis is made either if four major features are present, i.e. coloboma of the eyes, choanal atresia or stenosis, cranial nerve anomaly (especially nerve I (missing or decreased sense of smell), nerve IX and nerve X (swallowing difficulties and aspiration) and nerve VII (facial palsy)) as well as ear abnormalities or if three major and three minor features are present, i.e. heart defects, cleft lip and/or palate, esophageal atresia or tracheoesophageal fistula, kidney anomalies, genital anomalies, growth deficiency, typical CHARGE face with asymmetry and ptotic lids, palm crease or CHARGE behavior (perseverative and obsessive compulsive)1. CHARGE syndrome may be associated with the presence of esophageal atresia and/or tracheoesophageal fistula4. In contrast to postnatal features, typical prenatal features on ultrasound are not well established since only a small number of fetuses with this syndrome have been described prenatally. In 2012, Legendre et al. summarized 40 cases of CHARGE syndrome5 and described external ear abnormalities, arhinencephaly and semicircular canal agenesis as typical prenatal ultrasound features. However, arhinencephaly and semicircular canal agenesis are rather difficult to identify. In our case, CHARGE syndrome was prenatally misdiagnosed as esophageal atresia because no stomach was present in typical location; polyhydramnios was visible and we interpreted the herniated stomach in the posterior mediastinum as mediastinal pouch of the atretic esophagus. This case shows that paraesophageal hernia can occur in fetuses with CHARGE syndrome, mimicking esophageal atresia. Based on our observation, paraesophageal hernia and CHARGE syndrome is a potential differential diagnosis in the case of a eutrophic fetus with clinical signs of esophageal atresia. E. Tempfer-Bentz*†, R. B. Troebs‡, C. Sonntag§, G. A. Rezniczek† and C. Tempfer† †Department of Obstetrics and Gynecology, Ruhr University of Bochum, Bochum, Germany; ‡Department of Pediatric Surgery, Ruhr University of Bochum, Bochum, Germany; §Department of Radiology, Ruhr University of Bochum, Bochum, Germany *Correspondence. (e-mail: [email protected])