The authors declare no conflict of interest.
Article first published online: 7 DEC 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part A
Volume 161, Issue 1, pages 131–136, January 2013
How to Cite
Aldinger, K. A., Kogan, J., Kimonis, V., Fernandez, B., Horn, D., Klopocki, E., Chung, B., Toutain, A., Weksberg, R., Millen, K. J., Barkovich, A. J. and Dobyns, W. B. (2013), Cerebellar and posterior fossa malformations in patients with autism-associated chromosome 22q13 terminal deletion. Am. J. Med. Genet., 161: 131–136. doi: 10.1002/ajmg.a.35700
How to Cite this Article: Aldinger KA, Kogan J, Kimonis V, Fernandez B, Horn D, Klopocki E, Chung B, Toutain A, Weksberg R, Millen KJ, Barkovich AJ, Dobyns WB. 2012. Cerebellar and posterior fossa malformations in patients with autism-associated chromosome 22q13 terminal deletion. Am J Med Genet Part A 161A:131–136.
- Issue published online: 22 DEC 2012
- Article first published online: 7 DEC 2012
- Manuscript Accepted: 1 SEP 2012
- Manuscript Received: 29 MAR 2012
The 22q13.3 deletion causes a neurodevelopmental syndrome, also known as Phelan-McDermid syndrome (MIM #606232), characterized by developmental delay and severe delay or absence of expressive speech. Two patients with hemizygous chromosome 22q13.3 telomeric deletion were referred to us when brain-imaging studies revealed cerebellar vermis hypoplasia (CBVH). To determine whether developmental abnormalities of the cerebellum are a consistent feature of the 22q13.3 deletion syndrome, we examined brain-imaging studies for 10 unrelated subjects with 22q13 terminal deletion. In seven cases where the availability of DNA and array technology allowed, we mapped deletion boundaries using comparative intensity analysis with single nucleotide polymorphism (SNP) microarrays. Approximate deletion boundaries for three additional cases were derived from clinical or published molecular data. We also examined brain-imaging studies for a patient with an intragenic SHANK3 mutation. We report the first brain-imaging data showing that some patients with 22q13 deletions have severe posterior CBVH, and one individual with a SHANK3 mutation has a normal cerebellum. This genotype–phenotype study suggests that the 22q13 deletion phenotype includes abnormal posterior fossa structures that are unlikely to be attributed to SHANK3 disruption. Other genes in the region, including PLXNB2 and MAPK8IP2, display brain expression patterns and mouse mutant phenotypes critical for proper cerebellar development. Future studies of these genes may elucidate their relationship to 22q13.3 deletion phenotypes. © 2012 Wiley Periodicals, Inc.