Affiliations: Williams Syndrome Center, The Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA | Department of Pathology, Montefiore Medical Center, Bronx, NY, USA | Department of Genetics & Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA
Note:  Corresponding author: Lilian Cohen, Division of Medical Genetics, Department of Pediatrics, New York Presbyterian Hospital-Weill Cornell Medical College, 505 East 70th Street, 3rd Floor, New York, NY, USA. Tel.: +1 646 962 2205; Fax: +1 646 962 0273; E-mail: [email protected]
Abstract: Williams syndrome (WS) is a complex genomic disorder entailing distinctive facial dysmorphism, cardiovascular abnormalities, intellectual disabilities, unusual behavioral features, and a specific cognitive profile with considerable variability. Additional symptoms include endocrine abnormalities, renal anomalies and connective tissue disorders. We report a monozygotic twin patient with WS who presented with multicystic kidneys in the newborn period, and, in addition to the typical WS deletion at 7q11.23, was found to have a de novo 1.7 Mb deletion in the 17q12 region on microarray comparative genomic hybridization. The co-twin was selectively terminated at 23 wk of gestation after being diagnosed with bilateral multicystic dysplastic kidneys and anhydramnios. Review of the literature shows that deletion of chromosome 17q12, encompassing hepatocyte nuclear factor 1beta gene, is associated with cystic renal disease and is the first recurrent genomic deletion associated with maturity onset diabetes of the young. In addition, reports of female reproductive tract malformations and patients with neurocognitive or psychiatric phenotypes have recently been described. This review of the literature summarizes 47 other cases involving 17q12 deletions with wide variability in phenotype, possibly suggesting a contiguous gene syndrome. It is likely that the additional 17q12 deletion has played a role in modifying the phenotype in our patient. This case highlights the importance of using array comparative genomic hybridization in the clinical setting to uncover the etiology of atypical findings in individuals with known microdeletion syndromes.