De Novo Translocation (8;12) and Frontofacionasal Dysplasia in a Newborn Boy Julia Habecker-Green, 1 * Rizwan Naeem, 2 R. Michael Scott, 3 Camille Kanaan, 1 Lucy Bayer-Zwirello, 1 and Gabriel Cohn 1 1 Department of Obstetrics and Gynecology, Baystate Medical Center, Springfield, Massachusetts 2 Department of Pathology, Baystate Medical Center, Springfield, Massachusetts 3 Department of Neurosurgery, The Children’s Hospital, Boston, Massachusetts We describe a newborn boy one of triplets, whose karyotype was 46,XY,t(8;12)(q22;q21). Prenatal diagnosis of multiple craniofacial anomalies had been made. Following deliv- ery, the patient was thought to exhibit find- ings consistent with a diagnosis of frontofa- cionasal dysostosis. We hypothesize that one of the break points of this translocation may involve a gene essential to craniofacial development. Am. J. Med. Genet. 94:179–183, 2000. © 2000 Wiley-Liss, Inc. KEY WORDS: frontofacionasal dysplasia; frontofacionasal dysostosis; de novo trans- location (8;12) INTRODUCTION Frontofacionasal dysplasia or dysostosis (FFND, MIM 229400) comprises encephalocele, cranium bif- idum occultum, facial hypoplasia, blepharophimosis, telecanthus, S-shaped palpebral fissures, eyelid anomalies, deformed nostrils, nasal hypoplasia, bifid nose, and clefting of the lip, premaxilla, palate, and uvula. We report prenatal diagnosis and follow up to age 18 months of a boy with frontofacionasal dysplasia, and a de novo translocation (8;12). CLINICAL REPORT Our patient was the result of a triplet pregnancy conceived through intracytoplasmic sperm injection with subsequent zygote transfer. During a routine ul- trasound at 33 weeks of gestation, the following anomalies were noted in triplet C: bitemporal narrow- ing, bilateral anophthalmia, hypoplastic nose, small mouth, cleft lip, and stubby fingers with hitch-hiker thumb. The brain and heart were thought to be normal, and no other anomalies were detected. No anomalies were detected in triples A and B. Delivery occurred at 35 weeks of gestation, and an evaluation of newborn C was undertaken. The baby was a 1,017.5-g, 43.75-cm boy with a head circumference of 31.5 cm (25th–50th centile). The anterior fontanel was enlarged, measur- ing 4 × 4 cm with a wide metopic suture. Hypertelorism with telecanthus was noted; his outer canthal distance was 7 cm (> +2 SD) and inner canthal distance was 3.5 (> +2 SD). Blepharophimosis and probable anophthalmia were observed. The eyebrows were scant, especially medially. There was a small, flat nose and bilateral cleft lip. The middle finger length was 2.5 cm (mean to +2 SD), the hand length was 5.5 cm (mean), and the foot length was 9 cm (> +2 SD). Some lateral deviation of his fingers and toes was ob- served. A head computed tomography scan was per- formed and was significant for a possible naso- ethmoidal encephalocele with questionable extension of the frontal lobes into the nasal cavity, bilateral choa- nal stenosis or atresia, absent globes, partial agenesis of the corpus callosum, prominent cisterna magna, and several suture lines extending inferiorly from the an- terior fontanel to the level of the nasal bones. Magnetic resonance imaging evaluation did not confirm definite agenesis of the corpus callosum. These findings, with the results of the physical exam, were felt to be consis- tent either with frontonasal dysplasia sequence (FND) or FFND. Chromosomal studies were undertaken, and the peripheral karyotype was 46,XY,t(8;12)(q22;q21) (Fig. 1). Parental karyotypes were studied and were both normal showing the child’s translocation to be de novo. At age 5 months, the boy underwent a craniotomy to rule out and repair a suspected frontonasal encephalo- cele. Findings during this procedure were as follows: a very large anterior fontanel, a large wormian bone in the metopic suture, no olfactory apparatus, and a deep bowl-like configuration to the floor of the anterior fossa with a slight increase in gyral pattern in the overlying brain. There was no evidence of encephalocele, but the floor of the anterior fossa was inferiorly displaced. The brain structure looked relatively normal, although there were no olfactory nerves and probably no optic nerves. At 18 months, the boy presented to genetics for a *Correspondence to: Julia Habecker-Green, M.S., Division of Clinical and Reproductive Genetics, Baystate Medical Center, 759 Chestnut Street, Springfield, MA 01199. Received 21 October 1998; Accepted 21 April 2000 American Journal of Medical Genetics 94:179–183 (2000) © 2000 Wiley-Liss, Inc.