Further delineation of the 22q13 deletion syndrome

Abstract

A chromosomal deletion syndrome associated with a 22q13 microdeletion has previously been reported in approximately 75 children. We report six cases from Denmark with a deletion of 22q13. One was cytogenetically visible by conventional karyotyping, one was diagnosed by high resolution karyotyping after the demonstration of low arylsulfatase A activity. Two were diagnosed by high resolution CGH analysis, one was diagnosed by multisubtelomeric FISH analysis and one was diagnosed serendipitously as lack of the control signal in a FISH analysis for 22q11 deletion. One of the cases was a mosaic with 16% of cells showing two signals. The phenotype of the children included: generalized developmental delay, compromised language development, hypotonia, normal or accelerated growth and minor facial dysmorphism. Other features were partial agenesis of the corpus callosum, bilateral ureteropelvic stricture, gastroesophageal reflux and hearing loss. One case had a different phenotype, and showed a deletion as well as a duplication. The extent of the deletion was studied by quantitative PCR analysis of a number of DNA markers in the 22q13 region. The deletions varied in size, extending from 4.0 to 9.0 Mb. The clinical phenotype seemed rather similar although some specific features might be attributable to differences in deletions.

22q13.3 deletion syndrome: A recognizable malformation syndrome associated with marked speech and language delay

“…As above, several authors have described the phenotype in detail [Phelan et al, 2001;Luciani et al, 2003;Manning et al, 2004;Lindquist et al, 2005]. Clinical features are summarized in Table I, and Figures 1 and 2 depict affected children with deletion 22q13.3.…”

“…Subsequently, a number of case reports and small series of affected patients further delineated a recognizable del 22q13.3 syndrome [Doheny et al, 1997;Slavotinek et al, 1997;Fujita et al, 2000;Praphanphoj et al, 2000;Prasad et al, 2000;Anderlid et al, 2002;Barakat et al, 2004;Lindquist et al, 2005;Tabolacci et al, 2005;Babineau et al, 2006]. In addition, several larger series of affected individuals have delineated a widely variable disorder in which normal to accelerated growth, hypotonia and marked speech and language impairment are the most reproducible features.…”

A patient with the classic features of Phelan‐McDermid syndrome and a high immunoglobulin E level caused by a cryptic interstitial 0.72‐Mb deletion in the 22q13.2 region

“…It is believed that the SHANK3 gene, which maps to 22q13 region, is the major candidate gene for the neurologic features of the syndrome [Wilson et al, 2003]. If SHANK3 is responsible for most of the neurologic abnormalities in these patients, this would imply that the deletion proximal to SHANK3 might have a milder phenotype that is largely masked by the terminal deletion of SHANK3 [Wilson et al, 2008].Almost all of the 22q13 deletions published so far have been described as terminal [Luciani et al, 2003;Wilson et al, 2003;Manning et al, 2004;Koolen et al, 2005;Lindquist et al, 2005;Phelan, 2008]. Deletions of 22q13 terminal region are variable in size [Koolen et al, 2005;Lindquist et al, 2005;Wilson et al, 2008; How to Cite this Article: 806 Dhar et al, 2010; Bonaglia et al, 2011;Sarasua et al, 2011].…”

Unilateral Opercular Polymicrogyria in a Girl with 22q13 Deletion Syndrome

“…To the best of our knowledge this is the first case of brain cortical malformation described in a patient with 22q13 deletion syndrome. As the majority of the cases previously described the reported girl presented a terminal deletion of considerable extension involving several genes including SHANK3 [15,30,16,12,14,20]. Because none of the previously reported cases of haploinsufficiency of SHANK3 were associated with a cortical brain disorder is improbably that this gene is involved in this kind of structural abnormalities.…”

“…If SHANK3 is responsible for most of the neurological abnormalities in these patients, this would imply that deletion of the region proximal to SHANK3 might have a mild phenotype that could be masked by the terminal deletion of SHANK3. Almost all of the 22q13 deletions published have been described as terminal [15,30,16,12,14,20]. However, there are several cases identified in the literature that have been described as 22q13 interstitial deletion and that presented a phenotype similar to the 22q13 terminal deletion syndrome [27,24,8,29].…”