Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning.

Cerebra.

Unique socio-behavioural phenotypes are reported across different neurodevelopmental disorders. Here, the effects of adult familiarity and nature of interaction on social anxiety and social motivation were investigated in individuals with fragile X (FXS;n=20), Cornelia de Lange (CdLS;n=20) and Rubinstein-Taybi (RTS;n=20) syndromes, compared to individuals with Down syndrome (DS;n=20). The Social Anxiety and Motivation Rating Scale was employed whilst participants completed four social tasks, each administered separately by a familiar adult, and also by an unfamiliar adult. Compared to participants with DS, those with FXS and RTS exhibited high levels of social anxiety but similar levels of social motivation.Participants with CdLS showed heightened anxiety and reduced motivation only during interactions with an unfamiliar adult when active participation was voluntary.

BackgroundThe aim of this study was to examine executive functioning in adolescents and adults with Cornelia de Lange syndrome (CdLS) to identify a syndrome and age-related profile of cognitive impairment.MethodsParticipants were 24 individuals with CdLS aged 13–42 years (M = 22; SD = 8.98), and a comparable contrast group of 21 individuals with Down syndrome (DS) aged 15–33 years (M = 24; SD = 5.82). Measures were selected to test verbal and visual fluency, inhibition, perseverance/flexibility, and working memory and comprised both questionnaire and performance tests.ResultsIndividuals with CdLS showed significantly greater impairment on tasks requiring flexibility and inhibition (rule switch) and on forwards span capacity. These impairments were also reported in the parent/carer-rated questionnaire measures. Backwards Digit Span was significantly negatively correlated with chronological age in CdLS, indicating increased deficits with age. This was not identified in individuals with DS.ConclusionsThe relative deficits in executive functioning task performance are important in understanding the behavioural phenotype of CdLS. Prospective longitudinal follow-up is required to examine further the changes in executive functioning with age and if these map onto observed changes in behaviour in CdLS. Links with recent research indicating heightened responses to oxidative stress in CdLS may also be important.

Purpose of reviewWhilst previous reviews have extended descriptions of the behavioural phenotype of Cornelia de Lange syndrome (CdLS) significantly, potential changes with age across the lifespan have been neglected. Age-related difference in the behavioural phenotype constitutes preliminary evidence of change with age. Documenting and understanding the developmental trajectories of behaviours is informative as it enables identification of risk periods for behavioural challenges and compromised mental health. Recent findingsRecent cross sectional, longitudinal and mixed design studies report differing presentations of the behavioural phenotype across the lifespan. Of particular interest are autistic characteristics and behaviours consistent with compromised mental health, particularly anxiety and negative affect, which are reported to be more common and severe in older individuals. Preliminary evidence for identified causal pathways with consideration of biological, cognitive and environmental factors are discussed.