Association of Syndromic Mental Retardation and Autism with 22q11.2 Duplication

Abstract

We describe a 5.3-year-old girl with autism, mental retardation, hypotonia, marked speech delay, and mild dysmorphic features with a 22q11.2 duplication. Her mother carries the same duplication and presents cleft palate, and normal intelligence. The clinical and behavioural phenotype of this relatively new syndrome is very heterogeneous, with high variability also in the familiar cases. Up till now, about 50 cases of 22q11.2 duplication have been reported, but only three of them are associated with autistic disorders. We propose that in addition to 22q13.3 deletion syndrome, also 22q11.2 duplication should be suspected in a patient with unspecified dysmorphisms, mental retardation, autism, hypotonia, and severe speech delay.

autism - 22q11.2 duplication - chromosome 22 - DiGeorge/velocardiofacial syndrome - mental retardation

References

• 1 Antshel KM, Aneja A, Strunge L. et al . Autistic spectrum disorders in velo-cardio facial syndrome (22q11.2 deletion).  J Autism Dev Disord. 2007;  37 1776-1786
• 2 Cusmano-Ozog K, Manning MA, Hoyme HE. 22q13.3 deletion syndrome: a recognizable malformation syndrome associated with marked speech and language delay.  Am J Med Genet C. 2007;  145 393-398
• 3 de La Rochebrochard C, Joly-Hélas G, Goldenberg A. et al . The intrafamilial variability of the 22q11.2 microduplication encompasses a spectrum from minor cognitive deficits to severe congenital anomalies.  Am J Med Genet. 2006;  140 1608-1613
• 4 Hassed S, Vaz SA, Lee J. et al . Expanded phenotype on the 22q duplication syndrome.  Am J Hum Genet. 2004;  75 151
• 5 Jacquemont ML, Sanlaville D, Redon R. et al . Array-based comparative genomic hybridisation identifies high frequency of cryptic chromosomal rearrangements in patients with syndromic autism spectrum disorders.  J Med Genet. 2006;  43 843-849
• 6 Mukaddes NM, Herguner S. Autistic disorder and 22q11.2 duplication.  World J Biol Psychiatry. 2007;  8 127-130
• 7 Portnoï MF. Microduplication 22q11.2: A new chromosomal syndrome.  Eur J Med Genet. 2009;  52 88-93
• 8 Prasad SE, Howley S, Murphy KC. Candidate genes and the behavioral phenotype in 22q11.2 deletion syndrome.  Dev Disabil Res Rev. 2008;  14 26-34
• 9 Ramelli GP, Silacci C, Ferrarini A. et al . Microduplication 22q11.2 in a child with autism spectrum disorder: clinical and genetic study.  Dev Med Child Neurol. 2008;  50 953-955
• 10 Wentzel C, Fernström M, Ohrner Y. et al . Clinical variability of the 22q11.2 duplication syndrome.  Eur J Med Genet. 2008;  51 501-510

Correspondence