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Possible mechanisms and gene involvement in speech problems in the 22q11.2 deletion syndrome

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Summary

The 22q11.2 deletion syndrome represents a contiguous gene syndrome with a highly variable phenotype. To date, over 180 clinical features have been described. Studies have been done in order to identify the responsible genes. Several candidate genes such as TBX1 and COMT seem to be important in the development of the phenotype. One of the prevalent and serious problems encountered by patients with the 22q11.2 deletion is difficulty with speech. This may be due to a number of factors such as adenoid hypoplasia, muscle hypotonia, platybasia, upper airway asymmetry, and neuroanatomical abnormalities. The complex interaction of these factors leads to less favourable results after surgery to correct velopharyngeal insufficiency. This article offers a theoretical overview and proposes future research to investigate which factors are indeed responsible for the speech problems encountered by patients with the 22q11.2 deletion and identify responsible genes.

Section snippets

Clinical features

To date, over 180 clinical features have been associated with the deletion2, 3 (see Table 1). The features show great inter- and intrafamilial variability. This variability is independent of the size of the deletion.5 Physical manifestations have been described which involve every organ system. The first presenting symptom is usually a congenital heart defect. Characteristic facial features are small ears, flat cheeks, a bulbous nose, hypertelorism, and almond-shaped eyes (see Figure 1). An

Management

Currently no accepted global protocol in the management of 22q11.2 deletion syndrome exists. After the international 22q11.2 deletion conference in Marseilles, France in 2006 this is under development. In the Netherlands a national guideline for the management of 22q11.2 DS has been in use for several years.13 As a rule, patients diagnosed with the 22q11.2 deletion usually undergo a series of evaluations, including cardiac, palatal, immunologic, otolaryngologic/audiologic, and developmental

Speech difficulties

One of the characteristic features of 22q11.2 DS is the presence of speech difficulties. Several studies have shown that children with the deletion show delayed language onset.15, 16, 17 In addition, a number of other communication disorders has been described. These include articulation, language, resonance, and voice problems. Palatal abnormalities may cause hypernasal speech and nasal air emission. Secondary to palatal anomalies and velopharyngeal insufficiency (VPI), compensatory

Genetic basis

The majority of patients who are clinically suspected of 22q11.2 DS and subsequently undergo genetic testing have a 3.0 megabase deletion. Less than 10% of patients has a smaller 1.5 megabase deletion and only few cases have unique smaller deletions.5The most commonly deleted region of 22q11.2 is known as the DiGeorge Chromosomal Region (DGCR) and comprises approximately 2.0 megabases (see Figure 2). It can be assumed that haploinsufficiency of one or more genes in this region may be

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