22q 13 Deletion Syndrome: A Genetic Basis For Neurobehavioral Disorders?

Abstract

Neurobehavioral disorders pose a challenge to physicians, both in diagnostic and therapeutic aspects. Many neurobehavioral disorders have been identified to have a genetic basis such as the fragile X syndrome and the 22q11 deletion associated with the Velocardiofacial syndrome. We describe three children with a different and less well characterized deletion involving the most distal band of chromosome 22 (22q13), where the presentation entails deviant development, minor dysmorphism and autistic features.

All 3 patients had developmental delay and unusual behavioral features. All our patients exhibited normal to advanced growth. Patient 1 had an added feature in submucous clefting of the palate. Patient 2 and 3 shared features of autistic spectrum disorder. Results of cytogenetic analysis in the three patients are as follows: Patient 1 ( 46XX ish del (22) (q13.3) (D22S39- D22S75X2), Patient 2 (46XY, del(22)(q13.1), Patient 3 (ish del (22)(q13q13) (LSI ARSA-) de novo). Thus, all three patients appear to share a deletion affecting the terminal 22q13 region.

Literature review of the patients with 22ql3 deletion is presented. Initially, the deletion was detected using high resolution chromosome analysis. Recently a FISH probe (D22S39) through its fortuitous use as a control probe in testing for 22q11 deletions has been used to demonstrate this deletion. The phenotypic features in most of the cases described include marked expressive speech delay, deviant development and pervasive behaviors, minor motor delays, minor dysmorphism, with normal or exaggerated growth. While there remain gaps in our understanding of this particular deletion syndrome, we propose that patients with significantly delayed speech, deviant development and behavioral issues, and minor facial dysmorphism be screened for this deletion.