Variability of epilepsy, autism, brachydactyly, and other clinical features in familial and sporadic 2q37.3 deletion

Article type: Research Article

Authors: Shrimpton, Antony E. | Kessler, John A. | Shaffer, Lisa G. | Stack, Cindy | Jalali, Ali | Little, Robert | Goldstein, Joshua | Angle, Brad | Chary, Ajit | Coppinger, Justine | Mathison, David J. | Khan, Sophia | Poznanski, Andrew K. | Dobyns, William B. | Craig, David W. | Hoo, Joe J. | Sarco, Dean | Bassuk, Alexander G.

Affiliations: Department of Pathology, Upsate Medical University, Syracuse, NY, USA | Department of Neurology, Northwestern University, Chicago, IL, USA | Signature Genomics Laboratory LLC, Spokane, Washington, DC, USA | Department of Pediatrics, Northwestern University, Chicago, IL, USA | Department of Pediatrics, Children's National Medical Center, Washington, DC, USA | Department of Medical Imaging, Children's Memorial Hospital, Northwestern University, Chicago, IL, USA | Department of Genetics, University of Chicago, Chicago, IL, USA | The Translational Genomics Research Institute, Phoenix, AZ, USA | Department of Genetics, University of Toledo, Toledo, OH, USA | Department of Pediatrics, Harvard University, Boston, MA, USA | Department of Pediatrics, Graduate Program in Genetics, Neuroscience, and Molecular and Cellular Biology, University of Iowa, Iowa City, IA, USA

Note: [] Correspondence: Alexander G. Bassuk, MD, University of Iowa, Department of Pediatrics, Graduate Program in Genetics, Neuroscience and Molecular and Cellular Biology, 25 S. Grand Ave, Medical Laboratories Building Room 2158, Iowa City, IA 52242, USA. Tel.: +1 319 384 4648; Fax: +1 832 218 1026; E-mail: [email protected]

Abstract: Chromosomal microdeletion syndromes are frequently associated with neurological disease including epilepsy and behavioral abnormalities. Yet, for most microdeletions, neurological phenotypes are variable and the exact molecular cause of neurological disease is not yet understood. Terminal deletions in the long arm of chromosome 2 (2q37.3) are among the most common microdeletion syndromes diagnosed, and have been associated with epilepsy, autistic-like features, short stature, obesity, and brachydactyly type E (short 4th and 5th metacarpals and metatarsals). However, neither epilepsy nor any of the other clinical features are invariant in 2q37.3 deletion. To elucidate the genetic mechanisms underlying this clinical variability we report what is, to our knowledge, the first description of inherited 2q37.3 deletion (without other complex chromosomal rearrangements) in three family members and present two sporadic cases and accompanying chromosomal microarray data. The clinical features of the three familial and two sporadic cases combined with the chromosomal microarray results suggest that all of the clinical features seen in 2q37.3 deletion may be variably expressed.

Keywords: 2q37.3, microarray, microdeletion, epilepsy, autism, brachydactyly

DOI: 10.3233/JPN-2009-0312

Journal: Journal of Pediatric Neurology, vol. 7, no. 3, pp. 279-283, 2009