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PEDIATRICS Vol. 114 No. 2 August 2004, pp. 451-457

Terminal 22q Deletion Syndrome: A Newly Recognized Cause of Speech and Language Disability in the Autism Spectrum

Melanie A. Manning, MD^*, Suzanne B. Cassidy, MD, Carol Clericuzio, MD, Athena M. Cherry, PhD^||, Stuart Schwartz, PhD^¶, Louanne Hudgins, MD^*, Gregory M. Enns, MB, ChB^*, H. Eugene Hoyme, MD^*

^* Department of Pediatrics, Division of Medical Genetics, Stanford University School of Medicine, Stanford, California
Department of Pediatrics, Division of Human Genetics, University of California, Irvine, School of Medicine, Irvine, California
Department of Pediatrics, Division of Clinical Genetics/Dysmorphology, University of New Mexico School of Medicine, Albuquerque, New Mexico
^|| Department of Pathology, Stanford University School of Medicine, Stanford, California
^¶ Center for Human Genetics, Case Western Reserve University School of Medicine, Cleveland, Ohio

Objective. Cryptic subtelomeric chromosome rearrangements account for 6% to 10% of idiopathic mental retardation. As cytogenetic and molecular techniques have become more sophisticated, the number of genetic syndromes attributed to these microdeletions has increased. To date, 64 patients have been described in the literature with a more recently recognized microdeletion syndrome, del 22q13.3. The purpose of this study is to present 11 new cases of this recently described syndrome to delineate further the phenotype and to alert the clinician to another genetic condition that should be considered in the differential diagnosis of early hypotonia, delayed speech acquisition, and autistic behavior.

Methods. Eleven patients were evaluated in 3 academic institutions. Clinical features and results of cytogenetic testing were recorded and tabulated. Reasons for referral for genetic evaluation included developmental delay, severe expressive speech and language delay, and dysmorphic features.

Results. Age of presentation ranged from 5 months to 46 years. There were 10 female patients and 1 male patient. All of the patients exhibited delayed motor development, some degree of hypotonia, and severe expressive speech and language delay. Dysmorphic facial features included epicanthal folds, large cupped ears, underdeveloped philtrum, loss of cupid's bow, and full supraorbital ridges. Six patients exhibited autistic-like behaviors. Microscopically visible chromosome deletions were observed in 6 patients. In the remainder, the deletion was detected with the use of fluorescence in situ hybridization.

Conclusions. Hypotonia and developmental delay are nonspecific findings observed in many malformation and genetic syndromes. However, in association with severe speech and language delay and autistic-like behavior, this phenotype may be a significant indication to consider the 22q13 deletion syndrome as a potential cause.

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Key Words: 22q deletion syndrome • autism • speech and language disability • fluorescence in situ hybridization

Abbreviations: MR, mental retardation • FISH, fluorescence in situ hybridization • VCF, velocardiofacial • ARSA, arylsulfatase A • DGS, DiGeorge sequence • ProSAP2, proline-rich synapse associated protein 2

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Received for publication Jun 26, 2003; Accepted Nov 20, 2003.

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