International investigation of neurocognitive and behavioral phenotype in 47,XXY (Klinefelter syndrome): Predicting individual differences

47,XXY (KS) occurs in 1:650 male births, though less than 25% are ever identified. We assessed stability of neurocognitive features across diverse populations and quantified factors mediating outcome. Forty‐four boys from the Netherlands (NL) and 54 boys from the United States (US) participated. The Wechsler Intelligence Scales assessed intellectual functioning; the ANT program evaluated cognitive function; and the CBCL assessed behavioral functioning. ANOVA was used for group comparisons. Hierarchical regressions assessed variance explained by each independent variable: parental education, timing of diagnosis, testosterone, age, and nationality. Parental education, timing of diagnosis, and hormonal treatment all played an important role in neurocognitive performance. The observed higher IQ and better attention regulation in the US group as compared to the NL group was observed with decreased levels of behavioral problems in the US group. Cognitive measures that were different between the NL and US groups, i.e., attention regulation and IQ scores, were also significantly influenced by external factors including timing of diagnosis, testosterone treatment, and parental education. On the ANT, a cognitive phenotype of 47,XXY was observed, with similar scores on 9 out of the 10 ANT subtests for the NL and US groups. This study lays additional features to the foundation for an algorithm linking external variables to outcome on various neurodevelopmental measures.Development Psychopathology in context: clinical setting

Mapping autism risk loci using genetic linkage and chromosomal rearrangements.

International audienceAutism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 [corrected] families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs

Musculoskeletal abnormalities in a large international cohort of boys with 49,XXXXY

© 2020 Wiley Periodicals, Inc. 49,XXXXY is the rarest X and Y chromosomal variation, with an incidence of 1 in 80,000–100,000 live male births and has been associated with numerous musculoskeletal abnormalities. Data was collected from an international cohort of boys with 49,XXXXY over 10 years. Children were evaluated by a multidisciplinary team consisting of a pediatric orthopedist, a neurogeneticist, a neurodevelopmentalist, and two physical therapists. Increased rates of torticollis (32.4%), hamstring tightness (42%), radioulnar synostosis (67.6%), pes planus (65.2%), and other foot abnormalities (86.9%) were observed. Several anomalies increased with age, specifically hamstring tightness, kyphosis, and scoliosis. The elucidation of the orthopedic profile of this population is necessary in order to provide healthcare providers with current medical information. This research further supports the necessity for the comprehensive multidisciplinary treatment of boys with 49,XXXXY