Abstract
Introduction: The 22q11.2 deletion syndrome (22q11DS), mostly caused by the common deletion including the TBX- and COMT-genes (LCR22A-D), is highly associated with somatic anomalies. The distal deletion (distal of LCR22D) comprises the MAPK1-gene and is associated with specific heart defects. The rare central deletion (LCR22B-D) encompasses the CRKL-gene and shows predominantly urogenital anomalies. 22q11DS also differs in its neuropsychiatric profile: common deletion accompanied by schizophrenia-like psychoses and autism spectrum disorders, distal deletion by anxiety disorders, and central deletion by autistic-like behaviours. Objectives: Investigating genetic subtypes of 22q11DS. Aims: Achieving a targeted pharmacological treatment based on genetic sub-typing. Methods: Thirty-two patients with genetically proven 22q11DS, referred for detailed neuropsychiatric analysis. Results: Apart from two patients with distal deletion and one with central deletion, common 22q11.2 deletion was detected in 29 patients. Those with the common deletion were typified by a history of relapsing schizophrenia-like psychoses and partial non-response to conventional antipsychotics. In most patients, anxieties and mood instability were also manifest. The two patients with a distal deletion predominantly showed anxiety symptoms, while the behaviour of the patient with a central deletion was characterized by symptoms from the autism spectrum. Most patients with a common deletion could successfully be treated with clozapine or quetiapine, often combined with valproic acid. One patient with a distal deletion showed full remission upon treatment with citalopram (the second refused such a pharmacological intervention). The behaviour of the patient with central deletion improved upon contextual measures only. Conclusions: The genetic subtype of 22q11DS enables targeting of treatment strategy.
