Phenotypic Expansion and Further Characterization of the 17q21.31 Microdeletion Syndrome

Tiong Yang Tan ^1*, Salim Aftimos ², Lisa Worgan ³, Rachel Susman ⁴, Meredith Wilson ⁵, Sondhya Ghedia ⁶, Edwin P Kirk ⁶, Donald Love ⁷, Anne Ronan ⁸, Artur Darmanian ⁴, Anne Slavotinek ⁹, Jacob Hogue ¹⁰, John B Moeschler ¹¹, Jillian Ozmore ¹¹, Richard Widmer ⁴, Ravi Savarirayan ¹ and Gregory Peters ⁴

¹ Murdoch Children's Research Institute, Melbourne, Australia
² Northern Regional Genetic Services, Auckland Hospital, New Zealand
³ Department of Clinical Genetics, Liverpool Hospital, Australia
⁴ Children's Hospital at Westmead, Sydney, Australia
⁵ Childrens Hospital at Westmead, Sydney, Australia
⁶ Sydney Children's Hospital, Australia
⁷ Diagnostic Genetics, LabPLUS, Auckland Hospital, New Zealand
⁸ Hunter Genetics Unit, Waratah, NSW and University of Newcastle, Australia
⁹ Department of Pediatrics, Division of Genetics, University of California, San Francisco, United States
¹⁰ Department of Pediatrics, Division of Genetics, University of California, San Francisco, Australia
¹¹ Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire, United States

^* To whom correspondence should be addressed. E-mail: tiong.tan{at}ghsv.org.au.

Accepted 18 March 2009

Abstract

The recognition of the 17q21.31 microdeletion syndrome has been facilitated by high-resolution microarray technology. Recent clinical delineation of this condition emphasises a typical facial appearance, cardiac and renal defects, and speech delay in addition to intellectual disability, hypotonia and seizures. We describe eleven previously unreported patients expanding the phenotypic spectrum to include aortic root dilatation, recurrent joint subluxation, conductive hearing loss due to chronic otitis media, dental anomalies and persistence of fetal fingertip pads. Molecular analysis of the deletions demonstrates a critical region spanning 440 kb involving either partially or wholly five genes, CRHR1, IMP5, MAPT, STH and KIAA1267. These data have significant implications for the clinical diagnosis and management of other individuals with 17q21.31 deletions.