A Novel Distal 22Q11.21 Microduplication in a 43-Year-Old Male Patient with Mild Intellectual Disability, Social Cognitive Dysfunctions, and Anxiety.

Objective: The chromosome region 22q11.2 is highly susceptible to genomic rearrangements. It has become clear that genomic instability extends distally to the commonly deleted/duplicated region (Low Copy Repeats [LCR] A-D) and that a clear difference exists between the phenotypic presentation of patients with rearrangements in the common region versus that in the distal region (LCR D-H), particularly with respect to developmental and somatic issues. Microdeletions in the 22q11.2 distal region are typically associated with congenital heart defects whereas distal 22q11.2 microduplications are infrequently described and present with a smaller duplicated region and a rather unspecified phenotype.

Method: The present paper provides detailed assessments of a middle-aged male with mild intellectual disability, elsewhere diagnosed with autism spectrum disorder. Because of persisting functional complaints, he was referred for second opinion to a specialized outpatient department.

Results: High resolution SNP-based array analysis demonstrated a ~1.5 Mb distal microduplication in chromosome 22 flanked by LCR region 22C and LCR22E encompassing among others the disease gene MAPK1. No remarkable facial dysmorphisms were noticed. Autism spectrum disorder was ruled out and it was concluded that the patient was primarily suffering from mild intellectual disability and social cognitive dysfunctions with anxieties and suspicious social interactions, to be understood as a disorder within the anxiety spectrum.

Conclusions: The pattern of psychological and psychiatric phenomena was discussed against the background of findings on psychopathology in the chromosome 22 region demarcated by LCR breakpoints C and E. It was suggested that alterations in the MAPK1 gene due to either a deletion or a duplication enhance the vulnerability to develop a psychiatric disorder within the anxiety spectrum.