Neurocognition, adaptive functioning, and psychopathology in Kleefstra syndrome

Objective: The diagnostic yield for rare genetic causes for ID has increased tremendously over the last years. Studies that focus on sub-cohorts with known underlying genetic causes may enable to define more specific profiles that potentially could guide tailor made management. In our present study we aimed to examine if EHMT1 gene defects, which are also known as Kleefstra Syndrome (KS) in human, are associated with specific profiles for adaptive and maladaptive functioning. Participants and Methods: In total we studied 58 subjects with ID (28 males, 30 females): 24 with Kleefstra Syndrome and 34 controls. They were examined with the Vineland Adaptive Behavior Scale, mini PAS-ADD interview, Autism Diagnostic Observation Schedule and the Cambridge Neuropsychological Test Automated Battery (CANTAB) to obtain measures of adaptive and maladaptive functioning. This study has an explorative nature and statistical analysis were used to contrast the results (Fisher's exact test for prevalences, Mann-Whitney tests for subscale scores). Results: KS-participants have low levels of adaptive functioning. Autism spectrum disorders are extremely prevalent (about 100%, p=0,001). There are also signifantly high prevalences and symptom scores for depressive episodes (41,6%, p=0,043), obsessive compulsive disorders (33,3%, p=0,03) and psychotic symptoms (29,2%, p=0,005). The performance and results at the CANTAB are discussed in line with these. All together this results in a discriminating neuropsychiatric picture in KS patients. Conclusions: KS patients are extremely vulnerable to develop neuropsychiatric disorders and should be carefully monitored for this