Cornelia De Lange Syndrome Phenotype Research Articles

Clinical problems and everyday abilities of a group of Italian adolescent and young adults with Cornelia de Lange syndrome

Cornelia de Lange syndrome (CdLS) is a multiple congenital anomaly/mental retardation syndrome, characterized by distinctive facial features, generalized hirsutism, growth and cognitive dysfunction, microcephaly and limb abnormalities. Currently mutations of three different genes, NIPBL, SMC1A, and SMC3, are known to be related to the CdLS phenotype with an overall detection rate of about 50%. Few data are available regarding the level of autonomy in everyday life of CdLS patients. Due to the collaboration of the Italian parents' support group, we collected information regarding clinical and behavioral problems and everyday abilities of 45 CdLS patients between 13 and 39 years, using a specific multi-item questionnaire. To better analyze clinical information we divided our patients into three groups according to age: 13-20, 21-29, and over 30 years. Data from clinical, malformative and behavioral problems were not significantly different from those described for CdLS patients. Regarding personal autonomies this study showed the significant limitations of these individuals. It is interesting to observe that patients between 21 and 29 years, showed the best performance, while those over 30 had more severe difficulties. We suggest that these data be interpreted as a minimum level of autonomy achievable for CdLS adolescent/young adults, as the level of care, rehabilitation and stimulation of these patients has increased in the last 30 years.

Simultaneous analysis of the behavioural phenotype, physical factors, and parenting stress in people with Cornelia de Lange syndrome

Studies into the phenotype of rare genetic syndromes largely rely on bivariate analysis. The aim of this study was to describe the phenotype of Cornelia de Lange syndrome (CdLS) in depth by examining a large number of variables with varying measurement levels. Virtually the only suitable multivariate technique for this is categorical principal component analysis. The characteristics of the CdLS phenotype measured were also analysed in relation to parenting stress. Data for 37 children and adults with CdLS were collected. The type of gene mutation and relevant medical characteristics were measured. Information on adaptive functioning, behavioural problems, the presence of the autistic disorder and parenting stress were obtained through questionnaires and semi-structured interviews with the parents. Chronological age and gender were also included in the analysis. All characteristics measured, except gender, were highly interrelated and there was much variability in the CdLS phenotype. Parents perceived more stress when their children were older, were lower functioning, had more behavioural problems, and if the autistic disorder was present. A new perspective was acquired on the relation between the gene mutation type and medical and behavioural characteristics. In contrast with earlier research the severity of medical characteristics did not appear a strong prognostic factor for the level of development. Categorical principal component analysis proved particularly valuable for the description of this small group of participants given the large number of variables with different measurement levels. The success of the technique in the present study suggests that a similar approach to the characterisation of other rare genetic syndromes could prove extremely valuable. Given the high variability and interrelatedness of characteristics in CdLS persons, parents should be informed about this differentiated perspective.

Self‐injurious behaviour in Cornelia de Lange syndrome: 1. Prevalence and phenomenology

Self-injurious behaviour is frequently identified as part of the behavioural phenotype of Cornelia de Lange syndrome (CdLS). We conducted a case-control study of the prevalence and phenomenology of self-injurious behaviour (SIB) in CdLS. A total of 54 participants with CdLS were compared with 46 individuals who were comparable on key variables including age, degree of intellectual disability and wheelchair use, using questionnaire and observational measures. Clinically significant self-injury was not more prevalent in the CdLS group (55.6%), nor was it different in presentation from that seen in the comparison group. Hyperactivity, stereotyped and compulsive behaviours predicted clinically significant self-injury in all participants. Hand directed, mild self-injury was more prevalent in CdLS. The results show that clinically significant self-injury may not be part of the behavioural phenotype of CdLS but a specific body target for proto-SIB is more common.

The behavioural phenotype of Cornelia de Lange Syndrome: a study of 56 individuals

Few studies have investigated functional and behavioural variables of Cornelia de Lange Syndrome (CdLS) in a large sample of individuals. The aim of this study is to provide greater insight into the clinical, behavioural and cognitive characteristics that are associated with CdLS. In total, 56 individuals with CdLS participated in the study. During hospitalization, their mothers received a number of questionnaires to complete. The behavioural phenotype was investigated using the following scales: Developmental Behaviour Scale Primary Carer Version; Autism Behaviour Checklist; Childhood Autism Rating Scale. Our participants demonstrated some behavioural characteristics that are frequently associated with CdLS (hyperactivity, attention disorder, anxiety, compulsive disorders, self-injurious behaviour and autistic-like features). Our findings demonstrate the variability of behavioural characteristics in CdLS in addition to highlighting the contribution of some variables to both the CdLS behavioural profile and the developmental trajectory of the behavioural pattern. The behavioural characteristics identified in our sample were correlated with some clinical and functional aspects (chronological age, cognitive level and clinical phenotype). The variability of the behavioural profile in CdLS reflected the wide variability in cognitive and adaptive functioning across individuals and led us to conclude that there may be multiple behavioural phenotypes associated with the syndrome. Further comparative studies between CdLS and individuals with intellectual disability or other genetic syndromes may help to provide further understanding of the behavioural phenotype of CdLS.

Gastroesophageal reflux and Cornelia de Lange syndrome: typical and atypical symptoms.

As previously reported, gastroesophageal reflux (GER) is a frequent and severe medical complication of Cornelia de Lange syndrome (CDLS). The incidence of GER and the correlation between its presence and degree, and the clinical phenotype of CDLS (mild/classical according to Van Allen classification) were evaluated in a series of 43 patients. The pattern of presenting symptoms and their clinical evolution after medical or surgical treatment were also studied. A pathological GER was evident in 28/43 (65%) CDLS patients. The incidence of the complication was not significantly different in patients with classical (93.3%) vs. mild phenotype (82.3%), whereas a strong correlation was present between the degree of the esophageal damage and the clinical phenotype. A behavioral symptom (hyperactivity) was the most frequent sign associated with the condition (85%). Our data confirm the high occurrence of GER in CDLS patients, independently from the CDLS clinical phenotype. Regarding the severity of the esophageal lesions, a significant difference between the two clinical CDLS phenotypes was found. The evaluation of the presenting symptoms and of their evolution during the treatment emphasizes the importance of behavioral symptoms as major signs of esophageal damage in CDLS.

Analysis of intentional communication in severely handicapped children with Cornelia-de-Lange syndrome

Intentional communicative acts were assessed in 13 children with Cornelia-de-Lange syndrome (CdLS) with a severe mental disability and compared to a control group of Down and 5p (Cri-du-Chat (CdC)) syndrome children. The mean number of intentional communicative acts were significantly lower. Analysis of play behaviors revealed that the differences were specific for the communicative domain. They are part of a general behavioral characteristic of CdLS children with a severe mental disability which can be described as a lack of communication, emotional reactions and motility. A syndrome-specific low rate of communicative initiatives indicates a special problem for designing intervention programs which depend on opportunities for facilitating strategies. Learning outcomes The reader will learn about the behavioral phenotype of CdLS, distinctive communication problems and qualities of play behavior which are relevant for planning educational interventions in children with this syndrome.

Second‐trimester pregnancy associated plasma protein‐A levels are reduced in Cornelia de Lange syndrome pregnancies

Maternal serum samples were collected from 19 pregnancies which resulted in the birth of a child with the classical Cornelia de Lange syndrome phenotype ascertained by careful clinical review. Using specific immunoassays, the serum levels of pregnancy associated plasma protein-A, free-beta human chorionic gonadotrophin and inhibin A were investigated. Pregnancy associated plasma protein-A was detectable in all cases but the levels were significantly reduced in second-trimester maternal serum from 18 affected pregnancies. Expressed as multiples of the median (MOM), the results ranged from 0.03 MOM to 0.71 MOM with an overall median value of 0.21 MOM (Mann–Whitney p<0.001). From these data it is possible to estimate a probability that any given level of this serum marker is associated with an affected pregnancy. One further sample taken in the first trimester from an affected pregnancy at 11 weeks' gestation had a normal pregnancy associated plasma protein-A level (1.22 MOM). Less markedly reduced levels were found for free beta human chorionic gonadotrophin and inhibin A. We conclude that second-trimester maternal serum pregnancy associated plasma protein-A measurements may be of value as an adjunct to ultrasonography in the prenatal diagnosis of Cornelia de Lange syndrome. A table of likelihood ratios is presented. Copyright © 1999 John Wiley & Sons, Ltd.

Second-trimester pregnancy associated plasma protein-A levels are reduced in Cornelia de Lange syndrome pregnancies

Maternal serum samples were collected from 19 pregnancies which resulted in the birth of a child with the classical Cornelia de Lange syndrome phenotype ascertained by careful clinical review. Using specific immunoassays, the serum levels of pregnancy associated plasma protein-A, free-beta human chorionic gonadotrophin and inhibin A were investigated. Pregnancy associated plasma protein-A was detectable in all cases but the levels were significantly reduced in second-trimester maternal serum from 18 affected pregnancies. Expressed as multiples of the median (MOM), the results ranged from 0.03 MOM to 0.71 MOM with an overall median value of 0.21 MOM (Mann-Whitney p<0.001). From these data it is possible to estimate a probability that any given level of this serum marker is associated with an affected pregnancy. One further sample taken in the first trimester from an affected pregnancy at 11 weeks' gestation had a normal pregnancy associated plasma protein-A level (1.22 MOM). Less markedly reduced levels were found for free beta human chorionic gonadotrophin and inhibin A. We conclude that second-trimester maternal serum pregnancy associated plasma protein-A measurements may be of value as an adjunct to ultrasonography in the prenatal diagnosis of Cornelia de Lange syndrome. A table of likelihood ratios is presented.