7q11.23 Duplication syndrome: Physical characteristics and natural history. (3rd September 2015)

• Record Type: Journal Article
• Authors: Morris, Colleen A.; Mervis, Carolyn B.; Paciorkowski, Alex P.; Abdul‐Rahman, Omar; Dugan, Sarah L.; Rope, Alan F.; Bader, Patricia; Hendon, Laura G.; Velleman, Shelley L.; Klein‐Tasman, Bonita P.; Osborne, Lucy R.
• Is Part Of: American journal of medical genetics. Volume 167:Number 12(2015:Dec.)
• Page Start: 2916
• Page End: 2935
• Publication Date: 2015-09-03
• Subjects: 7q11.23 duplication syndrome -- Williams syndrome -- aortic dilation -- macrocephaly -- cerebellar vermis hypoplasia -- anxiety -- psychopathology -- developmental coordination disorder -- speech sound disorder; Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.37340
• Languages: English
• ISSNs: 1552-4825

Abstract

Abstract : In order to describe the physical characteristics, medical complications, and natural history of classic 7q11.23 duplication syndrome [hereafter Dup7 (MIM 609757)], reciprocal duplication of the region deleted in Williams syndrome [hereafter WS (MIM 194050)], we systematically evaluated 53 individuals aged 1.25–21.25 years and 11 affected adult relatives identified in cascade testing. In this series, 27% of probands with Dup7 had an affected parent. Seven of the 26 de novo duplications that were examined for inversions were inverted; in all seven cases one of the parents had the common inversion polymorphism of the WS region. We documented the craniofacial features of Dup7: brachycephaly, broad forehead, straight eyebrows, broad nasal tip, low insertion of the columella, short philtrum, thin upper lip, minor ear anomalies, and facial asymmetry. Approximately 30% of newborns and 50% of older children and adults had macrocephaly. Abnormalities were noted on neurological examination in 88.7% of children, while 81.6% of MRI studies showed structural abnormalities such as decreased cerebral white matter volume, cerebellar vermis hypoplasia, and ventriculomegaly. Signs of cerebellar dysfunction were found in 62.3%, hypotonia in 58.5%, Developmental Coordination Disorder in 74.2%, and Speech Sound Disorder in 82.6%. Behavior problems included anxiety disorders, ADHD, and oppositional disorders. Medical problems included seizures, 19%; growth hormone deficiency, 9.4%; patent ductus arteriosus, 15%; aortic dilation, 46.2%; chronic constipation, 66%; and structural renal anomalies, 18%. We compare these results to the WS phenotype and offer initial recommendations for medical evaluation and surveillance of individuals who have Dup7. © 2015 Wiley Periodicals, Inc.