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Neurodevelopmental disorders (NDDs) are considered synaptopathies, as they are due to anomalies in neuronal connectivity during development. DLG2 is a gene involved insynaptic function; the phenotypic effect of itsalterations in NDDs has been underestimated since few cases have been thoroughly described.We report on eight patients with 11q14.1 imbalances involving DLG2 , underlining its potential effects on clinical presentation and its contribution to NDD comorbidity by accurate neuropsychiatric data collection. DLG2 is a very large gene in 11q14.1, extending over 2.172 Mb, with alternative splicing that gives rise to numerous isoforms differentially expressed in brain tissues. A thorough bioinformatic analysis of the altered transcripts was conducted for each patient. The different expression profiles of the isoforms of this gene and their influence on the excitatory-inhibitory balance in crucial brain structures could contribute to the phenotypic variability related to DLG2 alterations. Further studies on patients would be helpful to enrich clinical and neurodevelopmental findings and elucidate the molecular mechanisms subtended to NDDs.

Syndromic neurodevelopmental disorders are usually investigated through genetics technologies, within which array comparative genomic hybridization (Array-CGH) is still considered the first-tier clinical diagnostic test. Among recurrent syndromic imbalances, 17q12 deletions and duplications are characterized by neurodevelopmental disorders associated with visceral developmental disorders, although expressive variability is common. Here we describe a case series of 12 patients with 17q12 chromosomal imbalances, in order to expand the phenotypic characterization of these recurrent syndromes whose diagnosis is often underestimated, especially if only mild traits are present. Gene content and genotype-phenotype correlations have been discussed, with special regard to neuropsychiatric features, whose impact often requires etiologic analysis.