7q11.23 Duplication syndrome: Physical characteristics and natural history.
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.
Department of Pediatrics, University of Nevada School of Medicine, Las Vegas, Nevada.
Colleen A
CA
Morris
Department of Psychological and Brain Sciences, University of Louisville, Louisville, Kentucky.
Carolyn B
CB
Mervis
Departments of Neurology, Pediatrics, and Biomedical Genetics, Center for Neural Development and Disease, University of Rochester Medical Center, Rochester, Nevada.
Alex P
AP
Paciorkowski
Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi.
Omar
O
Abdul-Rahman
Division of Medical Genetics, University of Utah, Salt Lake City, Utah.
Sarah L
SL
Dugan
Department of Medical Genetics, Kaiser Permanente, Portland, Oregon.
Alan F
AF
Rope
Northeast Indiana Genetics, Fort Wayne, Indiana.
Patricia
P
Bader
Department of Pediatrics, University of Mississippi Medical Center, Jackson, Mississippi.
Laura G
LG
Hendon
Department of Communication Sciences and Disorders, University of Vermont, Burlington, Vermont.
Shelley L
SL
Velleman
Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, West Virginia.
Bonita P
BP
Klein-Tasman
Departments of Medicine and Molecular Genetics and Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Lucy R
LR
Osborne
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002897:Chromosomes, Human, Pair 7; D002658:Developmental Disabilities / Q000209:etiology / Q000235:genetics; D005145:Face / Q000002:abnormalities; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D058627:Megalencephaly; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics; D018980:Williams Syndrome / Q000209:etiology* / Q000235:genetics; D055815:Young Adult
7q11.23 duplication syndrome; Williams syndrome; anxiety; aortic dilation; cerebellar vermis hypoplasia; developmental coordination disorder; macrocephaly; psychopathology; speech sound disorder