Invited symposium: Neuropsychological Phenotyping Bridges Clinical and Basic Research

Abstract

Symposium Description: Genetic disorders can initially manifest with a specific pattern of psychological dysfunctions and/or behavioural disorders. This holds for genetic disorders resulting from large chromosomal abnormalities but also for the many novel microdeletion syndromes that have been described recently. A well-known example of the first category is Klinefelter or XXY syndrome, while 17q21.31 microdeletion syndrome (17qMDS) and Kleefstra syndrome (KS) are examples of the last. KS was originally described as the 9q subtelomeric deletion syndrome associated with marked mental retardation, specific dysmorphisms, particular sleep disturbances, and progressive deterioration and apathy, suggestive for a ‘neurodegenerative phenotype’. Haploinsufficiency of the EHMT1 gene has proven to be the causative factor. 17qMDS, thought to be caused by MAPT haploinsufficiency, comprises moderate mental retardation, dysmorphisms and various congenital anomalies. Hypersociability has been suggested to be part of its behavioural phenotype. There is great variability in the degree to which genetic disorders are investigated on behavioural and neurocognitive variables. For instance, Noonan syndrome (NS), a relatively common autosomal dominant congenital disorder often caused by a mutation of genes in the Ras/MAP kinase pathway (e.g., PTPN11, KRAS, and SOS1), has been described from a neuropsychological perspective only very recently. In this symposium, an overview will be given of modern genetic analysis techniques followed by recent findings on neuropsychological and psychopathological phenotypes of 17qMDS, XXY, NS, and KS. It is concluded that in all of the above syndromes, neuropsychological examination was able to demonstrate specific patterns of neurocognitive development and social interaction. Findings will be discussed as to their potential to further clarify the genotype-phenotype relation and to establish individualized behavioural and clinical management programs.