7q11.23 Duplication syndrome: Physical characteristics and natural history

• Published in: American journal of medical genetics. Part A Vol. 167A; no. 12; pp. 2916 - 2935
• Main 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.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.12.2015; Wiley Subscription Services, Inc
• Subjects: 7q11.23 duplication syndrome; Adolescent; anxiety; aortic dilation; cerebellar vermis hypoplasia; Child; Child, Preschool; Chromosomes, Human, Pair 7; Columella; developmental coordination disorder; Developmental Disabilities - etiology; Developmental Disabilities - genetics; Face - abnormalities; Female; Humans; Infant; macrocephaly; Male; Megalencephaly; Pregnancy; Pregnancy Complications - genetics; psychopathology; speech sound disorder; Williams syndrome; Williams Syndrome - etiology; Williams Syndrome - genetics; Young Adult; anxiety; macrocephaly; psychopathology; developmental coordination disorder; aortic dilation; cerebellar vermis hypoplasia; 7q11.23 duplication syndrome; speech sound disorder; Williams syndrome
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.37340

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.