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Kleefstra Syndrome (KS) is a rare monogenetic syndrome, caused by haploinsufficiency of the euchromatic histone methyl transferase 1 (EHMT1) gene, an important regulator of neurodevelopment. The clinical features of KS include intellectual disability, autistic behavior and gastrointestinal problems. The gut microbiota, an important modifier of the gut-brain-axis, may constitute an unexplored mechanism underlying clinical KS variation. We investigated the gut microbiota composition of 23 individuals with KS (patients) and 40 of their family members, to test whether (1) variation in the gut microbiota associates with KS diagnosis and (2) variation within the gut microbiota relates with KS syndrome symptoms. Both alpha and beta diversity of patients were different from their family members. Genus Coprococcus 3 was lower in abundance in patients compared to family members. Moreover, abundance of genus Merdibacter was lower in patients versus family members, but only in participants reporting intestinal complaints. Within the patient group, behavioral problems explained 7% of beta diversity variance. Also, within this group, we detected higher levels of Atopobiaceae - uncultured and Ruminococcaceae Subdoligranulum associated with higher symptom severity. These significant signatures in the gut microbiota composition in patients with KS suggest that microbiota differences are part of the KS phenotype., (© 2023 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.)

Objective: Several instruments are available for measuring (aspects of) adaptive functioning, but knowledge is lacking about which is best to use to monitor patients with etiologically homogeneous neurodevelopmental disorders. In this study we compare the use of the Vineland-Z and ABAS-3 adaptive behavior scales in such a specific group., Method: Of patients with a molecularly confirmed diagnosis of Kleefstra syndrome, 34 were assessed with both the Vineland-Z and ABAS-3 of which 12 (35,3%) males and 22 (64,7%) females. Raw scores and developmental ages were calculated and a comparison between the instruments was done via correlation analysis., Results: Biological age ranged from 12 to 50 years old (median age of 23,1 ± 9,6 years). Pearson r correlation analyses show that the Vineland-Z and ABAS-3 assessments are highly interchangeable in this population. However, there are practical issues which require attention: (i) the use of ABAS-3 needs several versions to cover the whole adaptive spectrum, and (ii) the Vineland-Z discriminates more at the lower end of the adaptive functioning spectrum compared to the ABAS-3, but less at the higher end. An ideal instrument for this specific purpose is not yet available., Conclusions: We recommend that either the Vineland-Z, with modification of the dated items, the abridged version of the Vineland III, or a merge of the 0-4/517 ABAS-3 versions would work best to assess the entire spectrum of adaptive functioning adequately., Competing Interests: Competing interests: The ABAS-3 versions were directly provided by Hogrefe Uitgevers B.V. A research agreement was established between the publisher and the research group to allow use of the ABAS-3 before it was available on the Dutch market., (© 2023 Giovanni Fioriti Editore s.r.l.)

Background: Current developments in genetic strategies result in tracing an underlying genetic defect in the majority of neurodevelopmental disorders (NDD) patients, including those with normal functioning as well as intellectual disabilities. These genetic NDD are increasingly detected and still often underexposed in psychiatric practice., Aim: To improve (early) detection of these genetic NDD to contribute to psychiatric diagnostics and treatment, with the emphasis on reducing the mental vulnerabilities per developmental stage., Method: Overview of developments based on literature and guidelines., Results: Early detection includes both biological and environmental factors and provides tools for specific diagnostic procedures and treatment strategies. Within scientific research there is a tendency to translational research, which includes all levels from cell to the entire organism. This offers new insights and possibilities for personalized treatment., Conclusion: The current fragmented knowledge on these rare disorders needs to be bundled in the upcoming years. There is a lot of ground to be gained for psychiatric practice in this area.