Relevance of deletion breakpoint specification in 22q11.2 deletion syndrome: Clinical management of three illustrative patients

Objective: One of the most prevalent deletion syndromes is the common 22q11.2 deletion syndrome (22q11.2DS) that has a highly variable somatic and behavioural phenotype with different levels of intellectual disability and a variety of congenital abnormalities. Nowadays, in addition to the common deletion, three subtypes are distinguished based on the breakpoints of the deleted 22q11.2 region, the proximal and central deletion within the common deletion, and an additional distal deletion in 22q11.2. The involved region determines not only the somatic anomalies, but also seems to play a role in the behavioural and psychopathological presentation. Method: From a group of 35 patients with genetically proven 22q11.2DS and a record with extensive information on somatic, neuropsychiatric and neuropsychological data, for each deletion subtype, the patient with the most comprehensive dossier was selected. Their detailed case vignettes were analyzed as to the differences in psychopathology and treatment. Results: The common 22q11.2 deletion (involving both the proximal and central part) was dominated by a great variety of somatic anomalies and symptoms form the psychotic and mood spectrum, whereas the distal 22q11.2 deletion mainly showed congenital cardiac defects and anxiety bound psychopathology. In the central 22q11.2 deletion variant, autistic behaviours formed the core symptoms. In the common deletion, an atypical antipsychotic in combination with a mood stabilizer appeared to be most effective while an antidepressant agent induced long lasting effectiveness in the distal variant. The central variant typically presented with symptoms from the autism spectrum that did not warrant psychotropic intervention. Conclusions: The 22q11DS deletion region is of relevance for the range of somatic investigations and the assessment of differentiated psychopathology and may provide guidance for the treatment regimen.