The association of anophthalmia and esophageal atresia was first reported by Schenk et al.[1976] in a 28 mm human embryo. Since then, 15 further cases have been reported [Sassani and Yanoff, 1977; Rogers, 1988; Arroyo et al., 1992; Lurie et al., 1995; Sandler et al., 1995; Tucker et al., 1996; Ulman et al., 1996; Shah et al., 1997; Imaizumi et al., 1999; Menetrey et al., 2002; Messina et al., 2003; Petrackova et al., 2004], supporting the concept that the association should be considered a distinct syndrome. Although a genetic cause may be implicated, the etiology still remains unknown. We report a further patient with the association of esophageal atresia and anophthalmia and review the literature with particular emphasis on the associated anomalies, suggesting a role for the neural crest in its development. The patient was born by emergency cesarean section for fetal bradycardia at 38 weeks of gestation to a 29-year-old gravida 3, para 3. The present pregnancy was complicated by polyhydramnios and esophageal atresia was suspected on prenatal ultrasound at 36 weeks of gestation. During pregnancy, the mother smoked 5 cigarettes per day. Otherwise there was no known exposure to drugs or teratogens. The parents were nonconsanguineous, and the family history was positive for coronary disease in the maternal grandparents. Her birth weight was 2,956 g, length 48 cm (10th–50th centile), head circumference 34 cm (> 50th centile). Apgar scores were 9 and 10 at 1 and 5 min. At birth, in addition to a pure esophageal atresia without tracheo-esophageal fistula, bilateral anophthalmia, and a patent ductus arteriosus were found. There was no evidence of facial dysmorphism. The remainder of physical examination was normal. No vertebral or limbs anomalies were detected on radiographs. Karyotype was normal (46, XX). On day 3 of life, she underwent cervical esophagostomy and gastrostomy in another institution. At 5 months of age, she underwent esophageal replacement by gastric transposition, the cervical esophagus was anastomosed to the gastric fundus in the neck, and a feeding jejunostomy was performed. The baby was electively ventilated for three days post-operatively. The post-operative course was complicated by bilateral pleural effusions, which required drainage. Microcephaly (head circumference: 40 cm; 2nd centile for the age) was evident at a neurological examination. A brain CT scan was normal. By the age of 8 months she was able to take feeds by mouth, and the jejunal tube was removed. At 21 months, neurological motor examination revealed mild spastic diplegia and moderate hearing loss, which was secondary to recurrent episodes of otitis media. Developmental evaluation using the Reynell–Zinkin Scales for blind children, showed mild retardation, at 23 and 33 months. A subsequent brain MRI confirmed bilateral anophthalmia, with mild ventriculomegaly, some white matter changes posteriorly, and a normal pituitary stalk. At 4 years, she has no feeding problems, and weight and height are at the 3rd centile for her age. This is the 17th reported patient with the association of microphthalmia/anophthalmia and esophageal atresia. In addition to these malformations, all patients had one or more associated anomaly including central nervous system (CNS), craniofacial, urogenital, cardiovascular, and skeletal defects. Patients with the association of microphthalmia/anophthalmia and esophageal atresia may be divided in two groups.(A) Those with anophthalmia, all except one [Imaizumi et al., 1999] who are bilaterally affected and seem to have more severe associated anomalies.(B) Those with microphthalmia, with one …