ß 2008 Wiley-Liss, Inc. American Journal of Medical Genetics Part A 146A:2407–2411 (2008) Clinical Report Williams Syndrome in a Preterm Infant With Phenotype of Alagille Syndrome Prakesh S. Shah, 1 Prashanth Murthy, 1 David Skidmore, 2,3 Lisa G. Shaffer, 4 Bassem A. Bejjani, 4 and David Chitayat 2,3 * 1 Department of Pediatrics, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada 2 Department of Pediatrics, Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada 3 The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada 4 Signature Genomic Laboratories, LLC, Spokane, Washington Received 18 February 2008; Accepted 23 March 2008 We report on a preterm infant born at 31 weeks of gestation with a phenotype suggestive of Alagille syndrome, yet microarray analysis identified a deletion on 7q11.23 at the Williams syndrome locus. The infant died on day 18 of life with overwhelming sepsis. This case illustrates the importance of microarray analysis in diagnosing genetic conditions, especially in preterm babies whose facial and other clinical manifestations have not fully developed. ß 2008 Wiley-Liss, Inc. Key words: microarray; phenotype; genotype How to cite this article: Shah PS, Murthy P, Skidmore D, Shaffer LG, Bejjani BA, Chitayat D. 2008. Williams syndrome in a preterm infant with phenotype of Alagille syndrome. Am J Med Genet Part A 146A:2407 – 2411. INTRODUCTION Microarray-based cytogenetics has rapidly become adopted into the practice of clinical genetics. In array- based comparative genomic hybridization (aCGH), the patient and a control are differentially labeled and compared for DNA dosage differences. Depending on the design and genomic content, aCGH can be comprehensive and of very high resolution [Shaffer et al., 2007]. Williams syndrome is a genetic neurodevelop- mental disorder comprising supravalvar aortic steno- sis, mental retardation, a behavior phenotype and characteristic minor anomalies [Williams et al., 1961; Beuren et al., 1962, 1964; Nickerson et al., 1995]. Almost all cases are non-inherited and due to a deletion at 7q11.23 caused by an instability in a highly repetitive genomic region prone to unequal cross- over during meiosis [Nickerson et al., 1995]. The facial findings in newborn infants are not characteristic and thus cases with Williams syndrome are usually not diagnosed early unless the characteristic cardiac lesion, supravalvar aortic stenosis, is identified and prompts the specific FISH analysis. We report on a case of a preterm infant with Williams syndrome who presented with findings highly suggestive of Alagille syndrome. This case highlights the importance of microarray analysis in the clinical diagnosis of com- plex genetic conditions. CLINICAL REPORT The patient, a boy, was born to a 23-year-old G2P0SA1 mother at 31 weeks of gestation. The pregnancy was uneventful until 29 weeks when intrauterine growth restriction (IUGR) was detected (estimated fetal weight—793 g which was <3rd centile for gestational age). There was no history of bleeding, high blood pressure, diabetes mellitus or exposure to teratogens. Following counseling the couple decided to have amniocentesis, which showed a normal male karyotype (46,XY). Echo- cardiography showed a structurally normal heart. Delivery was by C-section for severe IUGR and breech presentation. The Apgar scores were 5 and 9 at 1 and 10 min, respectively. His birth weight was *Correspondence to: Dr. David Chitayat, The Prenatal Diagnosis and Medical Genetics Program, Mount Sinai Hospital, Ontario Hydro Generation Building, 700 University Avenue, 3rd floor, Rm. 3292, Toronto, Ontario, Canada. E-mail: dchitayat@mtsinai.on.ca DOI 10.1002/ajmg.a.32356