Research on women with the fragile-X premutation (FX-p) has been underrepresented within the field of behavioural phenotypes.
To understand whether the FX-p confers risk for autistic traits, depression and anxiety, independent of maternal status.
In study 1, mothers of children with fragile-X syndrome (M-FXp; n = 51, mean age 43 years (s.d. = 5.80)) were compared with mothers of autistic children (M-ASD; n = 59, mean age 42 (s.d. = 5.80)), mothers of children with Smith-Magenis syndrome (M-SMS; n = 27, mean age 39 (s.d. = 7.20)) and mothers of typically developing children (M-TD; n = 44, mean age 40 (s.d. = 4.90)). In study 2, the M-FXp group were compared with non-mothers with the FX-p (NM-FXp; n = 17, mean age 32 (s.d. = 9.20)), typically developed non-mothers (NM-TD; n = 28, mean age 31 (s.d. = 6.80)) and the M-TD group. All participants completed an online survey, including measures of IQ, autistic traits, anxiety, depression and positive affect.
In study 1: the M-FXp group reported more autistic traits than the M-TD group (P < 0.05, η2 = 0.046). Anxiety and parental stress were elevated in the M-FXp, M-SMS and M-ASD groups relative to the M-TD group (all P ≤ 0.003, η2 = 0.079-0.322). In study 2: a main effect of premutation status indicated that women with the FX-p report elevated autistic traits and anxiety (P ≤ 0.007, η2 = 0.055-0.060); this did not interact with maternal status.
The findings indicate that women with the FX-p show an increased risk for autistic traits and anxiety. This risk is specific to the presence of the FX-p and is not fully accounted for by maternal status or the stress of caring for children with neurodevelopmental disorders.
While 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.
Unique socio-behavioural phenotypes are reported for individuals with 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 social anxiety and reduced social motivation only during interactions with an unfamiliar adult when active participation was voluntary.
Psychopathology is prevalent in Williams (WS), fragile X (FXS) and Prader-Willi (PWS) syndromes. However, little is known about the potential correlates of psychopathology in these groups. A questionnaire study was completed by 111 caregivers of individuals with WS (n = 35); FXS (n = 50) and PWS (n = 26). Mean age was 26 years (range 12-57 years); 74 (67%) were male. Multiple regression analyses indicated that higher rates of health problems and sensory impairments predicted higher psychopathology in WS (p <.0001). In PWS, poorer adaptive ability predicted higher overall psychiatric disturbance (p =.001), generalised anxiety (p =.006) and hyperactivity (p =.003). There were no significant predictors in FXS. This study highlights dissociations in the potential risk markers of psychopathology between genetic syndromes. Implications for intervention are discussed.
Background: Self-injurious behaviours, such as head banging, hair pulling, skin picking and scratching, are common in individuals with autism. Despite high prevalence rates, there is a paucity of longitudinal research to refine models of risk and mechanism and inform service planning. In this longitudinal study, we investigated self-injury in a cohort of individuals with autism over 10 years to identify behavioural and demographic characteristics associated with persistent self-injury. Methods: Carers of 67 individuals with autism completed questionnaires relating to the presence of self-injury and relevant risk markers at T 1 (mean [SD] age in years 13.4 [7.7]) and T 3 (mean [SD] age in years 23.9 [7.7]) 10 years later. Forty-six of these also took part at T 2 (3 years after initial participation). Analysis assessed demographic and behavioural risk markers for self-injury, as well as the predictive value of items assessed at T 1and T 2. Results: Self-injury was persistent in 44% of individuals over the 10-year period, with behavioural characteristics of impulsivity (p <.001) and overactivity (p =.002), identified as risk markers for persistence. A predictive model of self-injury was derived from LASSO analysis, with baseline impulsivity, interest and pleasure, stereotyped behaviour, social communication and adaptive functioning predicting self-injury over 10 years. Conclusions: In this unique longitudinal investigation into the persistence of self-injury in a non-clinical sample of individuals with autism over a 10 year period, we have identified a novel, robust and stable profile of behavioural characteristics associated with persistent self-injury. Findings support an early intervention strategy targeted towards individuals identified to be at a higher risk of developing self-injurious behaviour.
Individuals with Cornelia de Lange syndrome (CdLS) have been reported to show comparatively high levels of flat and negative affect but there have been no empirical evaluations. In this study, we use an objective measure of facial expression to compare affect in CdLS with that seen in Cri du Chat syndrome (CDC) and a group of individuals with a mixed aetiology of intellectual disabilities (ID).
Observations of three groups of 14 children with CdLS, CDC and mixed aetiology of ID were undertaken when a one-to-one interaction was ongoing. Results: There was no significant difference between the groups in the duration of positive, negative or flat affect. However, the CdLS group displayed a significantly lower ratio of positive to negative affect than children in the other groups.
This difference partially confirms anecdotal observations and could be due to the expression of pain caused by health problems associated with CdLS or neurological expression of the CdLS gene in facial muscles related to expression of positive affect. However, further research is needed to directly test these possible associations.
Age-related behavioural change in Cornelia de Lange syndrome is poorly understood. We report a 7Â year follow-up study of adaptive behaviour, autism spectrum disorder symptomatology, language skills and behavioural characteristics in 30 individuals with Cornelia de Lange syndrome, compared with 18 individuals with Cri du Chat syndrome. The proportion of individuals with Cornelia de Lange syndrome meeting criteria for autism spectrum disorder on the Autism Diagnostic Observation Schedule increased, although patterns of change were complex. For both syndrome groups, absolute levels of adaptive ability were stable and receptive language improved, suggesting that changes over time do not result from an overall decline in ability. Reliable change index scores indicate heterogeneity within both groups in the occurrence of improvement or decline.
P.A. Mulder, S. Huisman, A.M. Landlust, Jo Moss, S. Piening, R.C. Hennekam, I.D.C. van Balkom, I. Bader, A.-M. Bisgaard, A. Brooks, A. Cereda, C. Cinca, D. Clark, V. Cormier-Daire, M.A. Deardorff, K. Diderich, M. Elting, A. van Essen, D. Fitzpatrick, C. Gervasini, G. Gillessen-Kaesbach, K.M. Girisha, Y. Hilhorst-Hofstee, S. Hopman, D. Horn, M. Isrie, S. Jansen, C. Jespersgaard, F.J. Kaiser, M. Kaur, T. Kleefstra, I.D. Krantz, P. Lakeman, D. Lessel, C. Michot, S.E. Noon, C. Oliver, I. Parenti, J. Pie-Juste, B. Puisac, F.J. Ramos, E. Redeker, C. Rieubland, S. Russo, A. Selicorni, Z. Tümer, R. Vorstenbosch, I.M. de Vries, T.L. Wenger, J. Wierzba (2019)Development, behaviour and autism in individuals with SMC1A variants, In: Journal of Child Psychology and Psychiatry and Allied Disciplines60(3)pp. 305-313
Blackwell Publishing Ltd
Introduction: Development and behaviour in Cornelia de Lange Syndrome (CdLS), including autism characteristics, have been described infrequently stratified to genetic cause and only a few studies have considered behavioural characteristics in relation to developmental level. Here, we describe the behavioural phenotype in individuals with CdLS with SMC1A variants. Methods: We performed an international, interdisciplinary study on 51 individuals with SMC1A variants. Results of questionnaire studies are compared to those in individuals with Down Syndrome and with Autism Spectrum Disorder. Results on cognition and self-injurious behaviour (SIB) are compared to those in individuals with CdLS caused by NIPBL variants. For Dutch participants with SMC1A variants we performed direct in-person assessments of cognition, autism, and added an interview and questionnaire on adaptive behaviour and sensory processing. Results: Individuals with SMC1A variants show a higher cognitive level and less SIB than individuals with NIPBL variants. Individuals with SMC1A variants without classic CdLS phenotype but with a Rett-like phenotype show more severe intellectual disability and more SIB compared to those with a CdLS phenotype. Autism is less present if outcomes in direct in-person assessments are evaluated taking developmental level into account compared to results based on a questionnaire. Conclusions: Behaviour in individuals with CdLS should be evaluated taking genetic cause into account. Detailed interdisciplinary approaches are of clinical importance to inform tailored care and may eventually improve quality of life of patients and families.
Background: Depressive symptomology and low affect are comparatively common in individuals with genetic disorders such as Cornelia de Lange syndrome. However, lifespan trajectories and associated person characteristics have not been examined. In this study, the trajectories for affect and associated behavioural characteristics were investigated in individuals with Cornelia de Lange syndrome with individuals with fragile X syndrome (FXS) comparable for chronological age and total number of behavioural indicators of ASD included for the purpose of contrast. Methods: A 7-year longitudinal study of affect (mood, interest and pleasure) was conducted in individuals with CdLS (n = 44) and FXS (n = 95). The trajectories of low affect were explored, as well as associations between Time 1 behavioural characteristics and affect at Time 1 and Time 3 (7 years later). Results: The CdLS group were lower in mood than the FXS group overall (p <.001). Interest and pleasure scores showed a significant decline over the lifespan for individuals with CdLS (p <.001) but not the FXS group. Lower level of ability at Time 1 was associated with lower mood at Time 1 and Time 3 in the FXS group only. Higher levels of ASD symptomology at Time 1 were associated with low mood and interest and pleasure in both syndrome groups at Time 1 and Time 3. Greater insistence on sameness at Time 1 was associated with lower mood at Time 1 in the FXS group and lower interest and pleasure at Time 1 and Time 3 in the CdLS group. Conclusions: Low affect in specific genetic syndromes may be associated with differing lifespan trajectories and behavioural profiles. Specifically, individuals with CdLS appear at risk for experiencing declines in levels of interest and pleasure whereas individuals with FXS show no significant change in the level of affect with age.
Background: Pitt-Hopkins syndrome (PTHS) is a genetic neurodevelopmental disorder associated with intellectual disability. Although the genetic mechanisms underlying the disorder have been identified, description of its behavioural phenotype is in its infancy. In this study, reported behavioural and psychological characteristics of individuals with PTHS were investigated in comparison with the reported behaviour of age-matched individuals with Angelman syndrome (AS) and Cornelia de Lange syndrome (CdLS).
Methods: Questionnaire data were collected from parents/caregivers of individuals with PTHS (n = 24), assessing behaviours associated with autism spectrum disorder (ASD), sociability, mood, repetitive behaviour, sensory processing, challenging behaviours and overactivity and impulsivity. For most measures, data were compared to data for people with AS (n = 24) and CdLS (n = 24) individually matched by adaptive ability, age and sex. Results: Individuals with PTHS evidenced significantly higher levels of difficulties with social communication and reciprocal social interaction than individuals with AS, with 21 of 22 participants with PTHS meeting criteria indicative of ASD on a screening instrument. Individuals with PTHS were reported to be less sociable with familiar and unfamiliar people than individuals with AS, but more sociable with unfamiliar people than individuals with CdLS. Data also suggested areas of atypicality in sensory experiences. Challenging behaviours were reported frequently in PTHS, with self-injury (70.8%) occurring at significantly higher rates than in AS (41.7%) and aggression (54.2%) occurring at significantly higher rates than in CdLS (25%). Individuals with PTHS also evidenced lower reported mood than individuals with AS.
Conclusions: Behaviours which may be characteristic of PTHS include those associated with ASD, including deficits in social communication and reciprocal social interaction. High rates of aggression and self-injurious behaviour compared to other genetic syndrome groups are of potential clinical significance and warrant further investigation. An atypical sensory profile may also be evident in PTHS. The specific aetiology of and relationships between different behavioural and psychological atypicalities in PTHS, and effective clinical management of these, present potential topics for future research.
A.D. Kline, Joanna Moss, A. Selicorni, A.-M. Bisgaard, M.A. Deardorff, P.M. Gillett, S.L. Ishman, L.M. Kerr, A.V. Levin, P.A. Mulder, F.J. Ramos, J. Wierzba, P.F. Ajmone, D. Axtell, N. Blagowidow, A. Cereda, A. Costantino, V. Cormier-Daire, D. FitzPatrick, M. Grados, L. Groves, W. Guthrie, S. Huisman, F.J. Kaiser, G. Koekkoek, M. Levis, M. Mariani, J.P. McCleery, L.A. Menke, A. Metrena, J. O'Connor, C. Oliver, J. Pie, S. Piening, C.J. Potter, A.L. Quaglio, E. Redeker, D. Richman, C. Rigamonti, A. Shi, Z. Tümer, I.D.C. Van Balkom, R.C. Hennekam (2018)Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement, In: Nature Reviews Genetics19(10)pp. 649-666
Nature Publishing Group
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.
Background: Hyperactivity and repetitive behaviour are characteristic features of fragile X syndrome (FXS). However, little is known about the influence of autism symptomatology on how these characteristics develop over time. We investigate the profiles and developmental trajectories of overactivity, impulsivity and repetitive behaviour, in males with FXS over three time points spanning 8 years. Method: Participants formed two subgroups, those who displayed elevated symptoms of autism at Time 1 (n = 37; Mage = 16.32; age range = 6.61-43.51) and those who did not (n = 32; Mage = 8.43; age range = 8.94-47.49). Results: Participants without elevated symptoms of autism showed a reduction in impulsivity and repetitive questioning over time, whereas those with elevated symptoms of autism did not. Differences between the two subgroups in several topographies of repetitive behaviour emerged at Time 3 only. Conclusions: These results further understanding of the relationship between autistic phenomenology and behavioural characteristics in FXS.
D. Adams, R.P. Hastings, C. Alston-Knox, R. Cianfaglione, K. Eden, D. Felce, G. Griffith, Jo Moss, C. Stinton, C. Oliver (2018)Using Bayesian methodology to explore the profile of mental health and well-being in 646 mothers of children with 13 rare genetic syndromes in relation to mothers of children with autism, In: Orphanet Journal of Rare Diseases13(185)
BioMed Central Ltd.
Background: It is well documented that mothers of children with intellectual disabilities or autism experience elevated stress, with mental health compromised. However, comparatively little is known about mothers of children with rare genetic syndromes. This study describes mental health and well-being in mothers of children with 13 rare genetic syndromes and contrasts the results with mothers of children with autism.
Methods: Mothers of children with 13 genetic syndromes (n = 646; Angelman, Cornelia de Lange, Down, Fragile-X, Phelan McDermid, Prader-Willi, Rett, Rubenstein Taybi, Smith Magenis, Soto, Tuberous Sclerosis Complex, 1p36 deletion and 8p23 deletion syndromes) and mothers of children with autism (n = 66) completed measures of positive mental health, stress and depression. Using Bayesian methodology, the influence of syndrome, child ability, and mother and child age were explored in relation to each outcome. Bayesian Model Averaging was used to explore maternal depression, positive gain and positive affect, and maternal stress was tested using an ordinal probit regression model.
Results: Different child and mother factors influenced different aspects of mental well-being, and critically, the importance of these factors differed between syndromes. Maternal depression was influenced by child ability in only four syndromes, with the other syndromes reporting elevated or lower levels of maternal depression regardless of child factors. Maternal stress showed a more complex pattern of interaction with child ability, and for some groups, child age. Within positive mental health, mother and child age were more influential than child ability. Some syndromes reported comparable levels of depression (SMS, 1p36, CdLS) and stress (SMS, AS) to mothers of children with autism.
Conclusions:Bayesian methodology was used in a novel manner to explore factors that explain variability in mental health amongst mothers of children with rare genetic disorders. Significant proportions of mothers of children with specific genetic syndromes experienced levels of depression and stress similar to those reported by mothers of children with autism. Identifying such high-risk mothers allows for potential early intervention and the implementation of support structures.