Patient 2, a female infant, was born to unrelated healthy Japanese parents. The father was 25 years old and the mother 24 years old when she was born. At 28 weeks of gestation, the mother was sent to our hospital after esophageal atresia was suspected in the fetus. Excess amniotic fluid, hydrocephalus, bilateral hydronephrosis, overlapping fingers and toes, high prominent forehead, hypertelorism, and depressed nasal root were observed in the fetus on ultrasonography (Fig. 2A-C). The female infant was delivered at 37 weeks and 4 days of gestation, weighing 3106 g and with a length of 47 cm. Soon after birth, she developed respiratory difficulty due to middle airway obstruction attributed to the posteriorly placed tongue and narrow nasal cavity. Esophageal atresia was not found on nasogastric tube examination. The patient showed a characteristic facial appearance with high prominent forehead, hypertelorism, upturned nostrils, midface hypoplasia, depressed nasal root, and micrognathia (Fig. 2D). She also had a large fontanel, malformed auricles, low-set ears, and overlapping fingers and toes (Fig. 2E). By 17 days after birth, her respiration had improved and oral milk feeding was started. Further examinations revealed mild hydrocephalus, hydronephrosis (Fig. 2F), normal heart structure, and normal external genitalia. No neoplasia was detected before she left our hospital at 30 days old. Peripheral blood was withdrawn for chromosomal and DNA examinations. GTG-banded chromosome examination revealed 46,XX. SETBP1 coding sequence analysis revealed a heterozygous guanine-to-adenine missense mutation at position 2608, predicting amino acid substitution (G870S).
This research was prospectively reviewed and approved by the Committee for Genetic Testing and Counseling at Tenshi Hospital in Japan.