Christine Cans

Cartographic study: breakpoints in 1574 families carrying human reciprocal translocations

Reciprocal translocations (rcp) are among the most common constitutional chromosomal aberrations in man. Using a European database of 1574 families carrying autosomal rep, a cartographic study was done on the breakpoints involved. The breakpoints are non-randomly distributed along the different chromosomes, indicating “hot spots”. Breakpoints of rep that result in descendants that are unbalanced chromosomally at birth are more frequent in a distal position on chromosomal arms, and 65% of them are localised in R-bands. Among the R-bands, bands rich in GC islands and poor in Alu repetitive sequences are more frequently the site of breakpoints, as well as bands that include a fragile site. This result suggests that the variation in degree of methylation in GC islands could be involved in chromosomal breakage and hence in chromosomal rearrangements.

Viability thresholds for partial trisomies and monosomies. A study of 1,159 viable unbalanced reciprocal translocations.

From a data base of 1,590 independent families with autosomal reciprocal translocations, 1,159 viable unbalances were studied and the lengths of their trisomy/ monosomy segments measured according to the method proposed by Daniel. About 5% of cases were found not to comply with Daniel viability criteria. The thresholds of viability vary with the mode of unbalance and with the sex of the carrier. Thus, new viability criteria are proposed as a guide for genetic counseling and prenatal diagnosis.

Logistic regression model to estimate the risk of unbalanced offspring in reciprocal translocations

The aim of this study was to estimate the risk of viable unbalanced offspring for a parental carrier of reciprocal translocation. On a large computerized database of reciprocal translocations we used logistic regression to model this risk. The status of the progeny is the outcome variable. Explanatory covariates are cytogenetic characteristics of the translocation, age and sex of the parental carrier, and potential viability of the gametes. The results obtained by the logistic model demonstrate the important role of certain variables such as the sex of the parental carrier and the R band length of the translocated segments. Within the group of lower risk (risk of viable unbalanced offspring less than 5%), 97% of the individuals are correctly classified with this model. For this group, the choice prenatal diagnosis can be best discussed by considering both the risk for viable unbalanced offspring and the risk of induced abortion following prenatal diagnosis.

Human reciprocal translocations: is the unbalanced mode at birth predictable?

Two methods of prediction for the risk of unbalance at birth were tested on a large data base of reciprocal translocation (1376 families): the pachyten diagram predictive method (PDPmethod) and the discriminant method (Dmethod). These method succeeded in correctly predicting the segregation mode in 66% of the data for the PDPmethod and in 80% of the data for the Dmethod. The quality of chromosome material (in particular R bands) must be taken into account for more accurate prediction. Some difficulties still exist in predicting the 3∶1 tertiary segregation mode, which can frequently be incorrectly classified as the adjacent 1 mode.

Adherence to Hypothermia Guidelines: A French Multicenter Study of Fullterm Neonates

Aim The objective of this study was to describe the French practice of hypothermia treatment (HT) in full-term newborns with hypoxic-ischemic encephalopathy (HIE) and to analyze the deviations from the guidelines of the French Society of Neonatology. Materials and Methods From May 2010 to March 2012 we recorded all cases of HIE treated by HT in a French national database. The population was divided into three groups, optimal HT (OHT), “late HT” (LHT) and “non-indicated” HT (NIHT), according to the guidelines. Results Of the 311 newborns registered in the database and having HT, 65% were classified in the OHT group, 22% and 13% in the LHT and NIHT groups respectively. The severity of asphyxia and HIE were comparable between newborns with OHT and LHT, apart from EEG. HT was initiated at a mean time of 12 hours of life in the LHT group. An acute obstetrical event was more likely to be identified among newborns with LHT (46%), compared to OHT (34%) and NIHT (22%). There was a gradation in the rate of complications from the NIHT group (29%) to the LHT (38%) group and the OHT group (52%). Despite an insignificant difference in the rates of death or abnormal neurological examination at discharge, nearly 60% of newborns in the OHT group had an MRI showing abnormalities, compared to 44% and 49% in the LHT and NIHT groups respectively. Conclusion The conduct of the HT for HIE newborns is not consistent with French guidelines for 35% of newborns, 22% being explained by an excessive delay in the start of HT, 13% by the lack of adherence to the clinical indications. This first report illustrates the difficulties in implementing guidelines for HT and should argue for an optimization of perinatal care for HIE.

Low but Increasing Prevalence of Autism Spectrum Disorders in a French Area from Register-Based Data

AbstractRegister-based prevalence rates of childhood autism (CA), Asperger’s syndrome (AS) and other autism spectrum disorders (ASD) were calculated among children aged 7xa0years old of the 1997–2003 birth cohorts, living in four counties in France. The proportion of children presenting comorbidities was reported. 1123 children with ASD were recorded (M/F ratio: 4.1), representing an overall prevalence rate of 36.5/10,000 children (95xa0% CI 34.4–38.7): 8.8/10,000 for CA (95xa0% CI 7.8–9.9), 1.7/10,000 for AS (95xa0% CI 1.3–2.3) and 25.9/10,000 for other ASD (95xa0% CI 24.2–27.8). ASD prevalence significantly increased (pxa0<xa00.0001) during the period under study. The proportion of children with an intellectual disability was 47.3xa0%, all other comorbidities were present in less than 5xa0% of the cases.n

Measuring the Concept of Impact of Childhood Disability on Parents: Validation of a Multidimensional Measurement in a Cerebral Palsy Population.

Living with a child with a disability can affect family life in various domains. Impacts on time, expenses, work, relationships within the family, social relationships and physical and psychological health can be observed. The Family Impact of Childhood Disability (FICD) is a specific instrument designed to assess this situation. Used in a cross-sectional survey, this questionnaire was extended to consider two missing aspects: impact on work and health (FICD+4). This paper addresses the psychometric qualities of the FICD in Europe among parents living with an adolescent with cerebral palsy. Expecting the FICD+4 could assess detailed impact dimensions, an exploratory analysis was conducted. We interviewed 242 families of 13- to 17-year-old adolescents with cerebral palsy living in Europe. Good psychometric properties were found in negative and positive FICD scales and in six underlying factors extracted from exploratory factor analysis on FICD+4. These results support the psychometric validity of the FICD in the assessment of the impact of disability in European families who live with an adolescent with cerebral palsy. They also highlight the multifaceted aspects of the impact of childhood disability on the family and suggest that the FICD+4 is a good tool for assessing specific negative impacts on time, finances, work, social relationships and positive impacts on parental feeling and family attitude. This scale needs further validation and could be helpful for research and clinical interventions.

Monitoring the prevalence of severe intellectual disability in children across Europe: feasibility of a common database

Our aim was to study the feasibility of creating a framework for monitoring and undertaking collaborative research on intellectual disability at the European level, based on existing databases of children with such disability.

The Definition of Cerebral Palsy

Cerebral palsy (CP) should not be considered as a diagnosis but as a label; it is an umbrella term. The definition is not sufficiently precise to guarantee agreement as to which patients to include under this label, but the additional inclusion criteria required are not yet internationally standardised.

What are we looking for in the field of paediatric 'neurodisability'?

There have been attempts in many countries to ascertain the number of children with special health care needs and/or chronic health conditions. Chronic conditions in children can comprise various disorders, e.g. allergies, bronchitis, heart conditions or disease, epilepsy, cerebral palsy (CP), kidney conditions or disease, intellectual disability, emotional, psychological or nervous disorders, and learning disabilities. The frequency of chronic conditions in children varies from 3% to 35%, with asthma and allergy often accounting for the main part of the variation. Thus, it is laudable to try to distinguish a disabled child with reduced respiratory or skin functions from a disabled child with a reduction or deviation in neuromusculoskeletal body functions. Re-defining the field of childhood disability may be beneficial for epidemiologists (monitoring trends) and clinical researchers (reproducible outcome), as well as for policy makers (type and amount of specific care required for a particular group of children). This is what Morris et al. have tried to do by proposing a challenging definition of the word ‘neurodisability’ to describe a rather complex field (although the paediatric sub-specialty of neurodisability exists in the UK). The proposed definition of neurodisability is challenging because restricting the field of childhood disability may exclude some children with disabilities, whilst others, (e.g. children with autism spectrum disorder [ASD]), will be categorized in the neurodisability group. A childhood disability attributed to changes in the neuromuscular system would be included in the neurodisability group, whilst a childhood disability attributed to changes in the musculoskeletal system would be excluded from this group. However, the International Classification of Functioning, Disability and Health classifies neuromusculoskeletal and movement-related functions in the same subcategory. Moreover, professionals caring for such children are most likely to consider disabilities in children with myopathy quite different from disabilities in children with CP, and from disabilities in children with ASD. The place of care and the type of care required by these groups of children are not the same, and in most countries the professionals who care for these children are different. Another issue is the attribution of the neurodisability condition to impairment of the brain and/or neuromuscular system, placing emphasis on the changes in body structure rather than on the changes in body function (e.g. movement, learning, and vision). Quite often the changes in body structure leading to the disability may be unknown or remain unrecognized. Disabled children with a similar clinical pattern might thus be excluded from the condition of neurodisability only because their disability was unrecognized or insufficiently explored. Taking the example of CP, the idea of extending the definition of CP to cover other childhood disabilities was suggested during an international workshop 10 years ago. The creditable intention at that time was to allow children with other disabilities to benefit from the same support as children with CP. However, it was acknowledged that CP was not an aetiological diagnosis, but rather a clinical descriptive term describing changes in numerous developing functions. For this reason the intention of widening the definition of CP was not endorsed. Childhood disability is a well-recognized domain, at least in Europe, and it covers various impairments. Specific subgroups of childhood disability are well identified – ASD, CP, neuromuscular diseases, deafness, blindness, intellectual impairment – and it might seem odd to add another category to the subgroups i.e. neurodisability. However, it must be recognized that some childhood disabilities are difficult to assess properly, depending on the scales available for measuring the impaired function and on the severity threshold. Thus, although wide, the spectrum of neurodisability may include only those disabilities that can be assessed in a sufficiently reliable way. This has to be explored further. Nevertheless, the interest of non-governmental organizations and families in such a broad grouping of different types of impairment is of utmost importance. Parents of children with ASD have recently been very active in advocacy and they might not favour ASD being categorized under the wider term of neurodisability, since it risks making the clearly defined needs of their children less understandable. On the other hand, parents with children who have a metabolic disease may be upset not to have their child included in this large ‘neurodisability’ group, since their children also require specific care. This commentary has questioned whether ‘neurodisability’ would be an appropriate new descriptive category in paediatric or public health research. However, future field studies with clear inclusion/exclusion criteria and severity level thresholds are needed to explore the usefulness of this proposal.