The duplication 17p13.3 phenotype: Analysis of 21 families delineates developmental, behavioral and brain abnormalities, and rare variant phenotypes. Issue 8 (27th June 2013)

• Record Type: Journal Article
• Authors: Curry, Cynthia J.; Rosenfeld, Jill A.; Grant, Erica; Gripp, Karen W.; Anderson, Carol; Aylsworth, Arthur S.; Saad, Taha Ben; Chizhikov, Victor V.; Dybose, Giedre; Fagerberg, Christina; Falco, Michelle; Fels, Christina; Fichera, Marco; Graakjaer, Jesper; Greco, Donatella; Hair, Jennifer; Hopkins, Elizabeth; Huggins, Marlene; Ladda, Roger; Li, Chumei; Moeschler, John; Nowaczyk, Malgorzata J.M.; Ozmore, Jillian R.; Reitano, Santina; Romano, Corrado; Roos, Laura; Schnur, Rhonda E.; Sell, Susan; Suwannarat, Pim; Svaneby, Dea; Szybowska, Marta; Tarnopolsky, Mark; Tervo, Raymond; Tsai, Anne Chun‐Hui; Tucker, Megan; Vallee, Stephanie; Wheeler, Ferrin C; Zand, Dina J.; Barkovich, A. James; Aradhya, Swaroop; Shaffer, Lisa G.; Dobyns, William B.;
• Is Part Of: American journal of medical genetics. Volume 161:Issue 8(2013:Aug.)
• Page Start: 1833
• Page End: 1852
• Publication Date: 2013-06-27
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.35996
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="ajmga35996-sec-0001" sec-type="section"> <p>Chromosome 17p13.3 is a gene rich region that when deleted is associated with the well‐known Miller–Dieker syndrome. A recently described duplication syndrome involving this region has been associated with intellectual impairment, autism and occasional brain MRI abnormalities. We report 34 additional patients from 21 families to further delineate the clinical, neurological, behavioral, and brain imaging findings. We found a highly diverse phenotype with inter‐ and intrafamilial variability, especially in cognitive development. The most specific phenotype occurred in individuals with large duplications that include both the <italic>YWHAE</italic> and <italic>LIS1</italic> genes. These patients had a relatively distinct facial phenotype and frequent structural brain abnormalities involving the corpus callosum, cerebellar vermis, and cranial base. Autism spectrum disorders were seen in a third of duplication probands, most commonly in those with duplications of <italic>YWHAE</italic> and flanking genes such as <italic>CRK</italic>. The typical neurobehavioral phenotype was usually seen in those with the larger duplications. We did not confirm the association of early overgrowth with involvement of <italic>YWHAE</italic> and <italic>CRK</italic>, or growth failure with duplications of <italic>LIS1</italic>. Older patients were often overweight. Three variant phenotypes included cleft lip/palate (CLP), split hand/foot with long bone deficiency (SHFLD), and a connective tissue phenotype resembling Marfan syndrome. The duplications in patients with clefts appear to disrupt <italic>ABR</italic>, while the SHFLD phenotype was associated with duplication of <italic>BHLHA9</italic> as noted in two recent reports. The connective tissue phenotype did not have a convincing critical region. Our experience with this large cohort expands knowledge of this diverse duplication syndrome. © 2013 Wiley Periodicals, Inc.</p> </sec> </abstract>