playalloa.co.uk Our aspiration is to offer an extensive range of creative play and social activities to as many local children and adults with disabilities and additional support needs as possible. This includes the provision of user services such as play sessions, social groups, adult life skills workshops, playschemes, volunteer befriending, parent information sessions and respite care and support opportunities. plusforthvalley.org.uk Starting in 1988 as one project PLUS has grown over the years, introducing new projects which target specific age ranges, support needs and individual outcomes. Services are primarily separated by age, into our under 5’s service, children and young people from ages 5 -17, and our adults services which caters to those over 18 years of age.

ayrshiresportsability.org.uk Ayrshire Sportsability is an investment in the future of people with a disability. These people will benefit from our activities by meeting other people, taking part in new and exciting sports, taking up sports regularly, developing further and taking part in competitive sports, in partnership with Scottish Disability Sport. affinitytrust.org We are committed to doing our very best for the people we support and never giving up on someone we support. We are Reliable and always do what we say we will do. We are Honest and open in all of our relationships and transactions. We are Respectful of others, their views and their right. We are Inclusive in how we value diversity, support equality of access to opportunities and challenge discrimination. We are Creative and flexible in our thinking, in our work and in how we use our resources.

affinitytrust.org We are c ommitted to doing our very best for the people we support and never giving up on someone we support . We are Reliable and always do what we say we will do . We are Honest and open in all of our relationships and transactions . We are Respectful of others, their views and their right . We are Inclusive in how we value diversity , support equality of access to opportunities and challenge discrimination . We are Creative and flexible in our thinking, in our work and in how we use our resources.

parent-to-parent.org A voluntary organisation which supports parents of children with additional support needs, whether physical, learning, sensory or behavioural which is associated with the disability. It also supports parents of children who are seriously or terminally ill or parents who have suffered a bereavement of a child. It provides advocacy for children and young people with additional needs. All families must live in Angus, Dundee or Perth & Kinross.

vsa.org.uk/richmondhill-house VSA’s Richmondhill House offers independent residential and community based support and assessments for children from birth to five years and their families. Both residential and outreach support is offered to families where child protection and/or child care issues have been identified.

camphillwellbeing.org.uk We are a Scottish charity supporting the wellbeing of patients and their families through an integrated, person-centred approach to health, education and social care. Our team has over 20 years of experience working with children, young people and adults who have learning disabilities and additional support needs. archway.org.uk Archway’s purpose is to create a network of care which supports the individual and the family, values their uniqueness, upholds their rights and respects their dignity.

Lynn K. Paul ( Senior Research Scientist at California Institute of Technology, Director of the Corpus Callosum Research Program, Founding President of the National Organisation of Disorders of the Corpus Callosum, NODCC in 2002) The research led by Dr Lynn Paul has focused on cognition and social skills in individuals with primary ACC. Dr Paul has worked closely with Prof Warren Brown on defining what they see as the core syndrome of ACC, how this manifests in everyday life and throughout the lifespan. An important finding is the pattern of strengths and weaknesses often seen in individuals with primary ACC; skills that can be consolidated with practice and overlearning are achieved well, but difficulties arise with more complex, novel, or open-ended tasks. Dr Paul outlined the following as examples: good basic reading skills, but relatively poor reading comprehension good rote learning of simple calculations, but poor mathematical problem solving strong basic language skills, but difficulties understanding the subtleties in language that occur in everyday conversation, such as non-literal expressions and humour Not being able to appreciate second-level meanings in language can lead to many social vulnerabilities; Dr Paul has found high-functioning individuals with ACC may not reliably determine whether someone is being sincere or sarcastic, with an over-tendency towards thinking someone is being sincere. They also had some problems identifying emotions as conveyed by actors, with particular difficulty with negative emotions such as sadness, anger and fear. Interestingly, a recent study found individuals with ACC did not look at the eye region as much as typically developing controls when asked to judge how someone was feeling from a photograph, and this seemed to contribute to their difficulty in correctly identifying emotions. Difficulties appreciating the intended meaning behind statements, coupled with misreading emotional information, leads to the suggestion that behaviours seen in individuals with ACC may overlap with those on the autism spectrum. Indeed, in a study of adults with ACC, 31% (8 from 26) presented with an autism spectrum disorder, with others being on the borderline range showing impairments in social interaction and communication. Dr Paul observed that children with primary ACC who are generally functioning well during early childhood seem to “grow into their difficulties” with behavioural and social problems becoming apparent in later childhood and adolescence. It is thought that as the complexity of social information increases with age, as well as higher expectations, difficulties become more visible. However there are few studies that track early development and these problems may be apparent in younger children with ACC, but have not yet been systematically studied. In response to this Dr Paul is conducting a longitudinal study of infants with ACC along with Prof Jed Elison ( Institute of Child Development and Department of Pediatrics, University of Minnesota ). This is the first study looking at the behavioural impact of disorders of the corpus callosum from birth into early childhood. Information is being collected from families through online questionnaires with the aim to better understand how ACC influences behaviour and neurological development during this critical period. Knowing these factors will help in the development of more effective intervention methods and support children and adults with ACC. For more information about this study and how to enrol go to: http://emotion.caltech.edu/?page_id=11851

Warren S. Brown (Professor of Psychology and Director of the Lee Travis Research Institute at the Graduate School of Psychology, Fuller Theological Seminary, Pasadena, California) Prof Warren S. Brown is involved in experimental neuropsychological research related to the functions of the corpus callosum. Over the last 20 years his laboratory has conducted one of the largest studies so far on the cognitive and social profiles of individuals with agenesis of the corpus callosum. His research team is particularly interested in studying the consequences of ACC in individuals who are functioning well overall but may have subtle problems in areas such as learning and memory, language, theory of mind, personality and emotion processing. From a series of experiments conducted over the years, Prof Brown describes the following as the “core syndrome” of ACC: (1) reduced interhemispheric integration of sensory and motor information, (2) reduced cognitive processing speed, and (3) deficits in complex reasoning and novel problem solving. These difficulties are said to stem from the reduced communication between the two hemispheres of the brain and is evident in different domains of functioning such as cognition, behaviour and social contexts. Prof Brown has found that simple visual and tactile information can be transferred between hemispheres in individuals with ACC, but encounter difficulty with more complex information. For example, adults with ACC could correctly judge whether two letters presented separately in the left and right visual fields were the same or different; however they took longer and made more errors when asked to judge if two patterns were the same or different. It was suggested that only a limited amount of information can be transferred between the two hemispheres in ACC and alternative pathways were likely being used.

Paul Lockhart (Associate Professor, Co-Director Department of Genetics, Bruce Lefroy Centre, Murdoch Children’s Research Institute, Royal Children’s Hospital, Victoria, Australia) As a geneticist, Dr Paul Lockhart outlined revolutionary approaches in technology that has led to identifying the genetic causes of many developmental disorders, including ACC. There are about 6,000 different conditions described in literature, but scientists only know the genetic basis for about half of them. There have been remarkable breakthroughs in methodologies (e.g., high-density microarrays, next-generation sequencing), which have resulted in the “golden-age” of gene discovery. Analyses, which used to take weeks to process, can now take half-an-hour at a much-reduced cost. There are still many challenges in the field and finding a causative change can be difficult. Detecting an alteration in a single gene is said to be equivalent to finding a single typo in 300 copies of the entire Harry Potter series! There are also natural variations found in everyone’s genes, and most are not related to a condition. In order to confidently state that a particular gene is likely to be the cause, scientists need to match up gene mutations and symptoms across several children to find common features. There are now large population databases available, where thousands of individuals have had their genes sequenced. Multiple comparisons can therefore be made that will add to the certainty of diagnosis. One such study based in the UK, Deciphering Developmental Disorders (DDD), has been extremely successful in advancing clinical genetic practice for children with developmental disorders. Although data collection has ended, analysis from the DDD study is on-going and over 30 new genetic conditions have been identified from analysing samples from over 13,000 families. Dr Lockhart is confident that understanding the genetic basis of disorders is the key to personalised medicine. It will enable families to have more accurate information on diagnosis and outcome, as well as provide the opportunity to develop targeted treatments in the future.

Elliott Sherr (MD, Professor in Neurology and Pediatrics, Institute of Human Genetics and the Weill Institute of Neurosciences, University of California, San Francisco, UCSF) Prof Elliott Sherr is a Child Neurologist and co-directs the Comprehensive Center for Brain Development at UCSF. His research team studies the genetic and biological mechanisms of disorders of brain development including epilepsy, autism and agenesis of the corpus callosum. They have found that both inherited and non-inherited (i.e., spontaneous) genetic events play an important role in causing brain malformations. Prof Sherr described how the field of genetic testing has moved rapidly in the last 15 years. In 2003, the state of the art in genetic testing involved looking at chromosomes under a microscope; however our knowledge of genetic disorders was limited – testing 100 individuals would only result in about 8 receiving a genetic diagnosis. Modern sequencing tools have transformed the way that geneticists have been able to identify specific gene mutations, with around 30 to 45% of individuals with ACC now having an identifiable genetic cause. The likelihood of receiving a diagnosis increases if the individual has several congenital abnormalities, such as heart or vision defects. ACC is well known to have a wide range of outcomes and this variability is likely to be related to the diversity in genetic causes that have been found. Knowing more about which specific genes influence the development of the corpus callosum allows for a better understanding of ACC and can remove a large amount of uncertainty for families. Receiving a genetic diagnosis can also impact on other areas of family life including future treatment options, social support and family planning. As a case example, Prof Sherr described the recent discovery of the DDX3X gene mutation, which primarily affects girls due to its location on the X-chromosome. It has been identified in about 200 individuals to date and may be the cause of 1 to 3% of all intellectual disabilities in females. The DDX3X gene mutation has also been linked to seizures, autism, low muscle tone, abnormalities of the brain such as a thinner corpus callosum, and slower physical developments. The discovery of this gene mutation has led to the establishment of the DDX3X Foundation, a non-profit organisation, which is dedicated to supporting research, connecting families, and raising awareness.

Linda Richards (Professor of Neuroscience and Deputy Director, Queensland Brain Institute at the University of Queensland; Patron and Scientific Advisor of AusDoCC, the Australian family support group for Disorders of the Corpus Callosum). Prof Linda Richards is a leading developmental neuroscientist who has conducted pioneering work in how the brain is normally wired during development and what mechanisms may be involved when this process is disrupted. Traditional views of brain development regard the process as hardwired with genes predetermining how brain structures mature. With more modern research methods available, there is evidence that brain development is an adaptive and flexible process with the on-going interaction between genes and the environment playing a crucial role. Researching individuals with disorders of the corpus callosum (DCC) provides a unique insight into the underlying mechanisms that control the plasticity of the brain and in particular, the development of the neuronal connections between the hemispheres. Prof Richards and colleagues have found the brain can rewire itself during development and produce long-range projections between different brain areas. They are trying to understand how different patterns of brain wiring may relate to the cognitive profile of the individual with DCC; for example, some connections may be essential, while others could be compensated for and not as essential as previously thought. Understanding the role of different patterns of brain wiring could help explain why individuals with DCC have widely different symptoms and outcomes. A fascinating line of enquiry into the formation of the corpus callosum is to study the mechanisms that led to the evolution of this structure. Interestingly, not all mammals have a corpus callosum; it is present in placental mammals but did not evolve in marsupials and egg-laying monotremes. Instead, their hemispheres communicate by using a simpler network of nerve fibres. Being based in Australia, Prof Richards and her laboratory team* are in a prime position to study early brain formation in marsupials. They have extensively studied a tiny species of marsupial called the fat-tailed dunnart. This mouse-like creature is born at a very early stage of brain development, just when the nervous system is beginning to form. As most of its cortical development occurs while the joey is inside the mother’s pouch, rather than the uterus, scientists have easy access to studying and manipulating this process – simply by opening up the pouch! This exciting new scientific approach has allowed researchers to gain crucial insights into the early mechanisms of brain formation as well as genetic and environmental influences. For example, the Satb2 gene, which has been found to contribute to the production of neurons that form the corpus callosum, is also present in the fat-tailed dunnart. This gene may instead have a role in forming other connections such as the anterior commissure in marsupials. Prof Richards and her laboratory team have also used MRI scans to examine the brains of marsupials and monotremes, and have found that nerve fibres that connect the hemispheres are arranged in a specific pattern, very similar to those found in the corpus callosum. This has led to the conclusion that there are specific ways in which the hemispheres prefer to connect in all mammals, and the principles that guide this formation must originate very early on in mammalian evolution. This provides evidence of a very ancient network, from which the corpus callosum evolved, possibly as a means to expand the existing hemispheric connections, rather than being a structure that evolved independently. These new findings may help our understanding of conditions with abnormal brain connectivity, including DCC. Prof. Richards’ laboratory members are: Dr Rodrigo Suarez Dr Jens Bunt Dr Laura Fenlon Dr Peter Kozulin Dr Ryan Dean Dr Kok-Siong Chen Dr Timothy Edwards Dr Annalisa Paolino Dr Elizabeth Haines Dr Caitin Bridges Ms Ching Moey Mr Jonathan Lim Ms Laura Morcom Mr Tobias Bluett Ms Yunan Yi Ms Donna Simon If you want to know more about who the Laboratory members are, please follow the following link. https://qbi.uq.edu.au/richardsgroup

Fernanda Tovar-Moll (Adjunct Professor, National Center of Structural Biology and Bioimaging at Federal University of Rio de Janeiro, and co-founder and president of the D’Or Institute for Research and Education, Rio de Janeiro) Prof Fernanda Tovar-Moll and her colleagues are interested in how the brain reorganises itself following a disruption in early development. Her research team uses sophisticated brain imaging methods and found the two hemispheres of the brain still manage to communicate with each other and transfer information despite the absence of the corpus callosum. This suggests that alternative pathways can be formed that may be compensatory in nature. For example, the bundles of axons normally destined to cross the corpus callosum can become rerouted when the normal developmental process is interrupted. These white matter bundles (e.g., Probst bundles and sigmoid bundles) still play an important role in connecting brain regions and are involved in the “long-range” transfer of information between hemispheres.

Once a person has received a diagnosis the help available will be dependent on their age and level of development and learning. However, many therapies and supports may help individuals with ACC and other disorders of the corpus callosum lead more successful lives. Children Changes in the corpus callosum are often diagnosed during childhood because of concerns about development, speech, or other problems such as seizures. It is likely that your child will have had a number of investigations as well as the brain scan such as blood and urine samples. This is often a time where there are a number of appointments with different professionals, including an ophthalmologist (eye specialist), endocrinologist (hormone specialist) and clinical geneticist for their opinions. This can be a frustrating time as it can feel that no-one knows what is wrong with your child. The majority of children will have a paediatrician (often a community paediatrician) who will be able to assess their development, coordinate their care and put you in touch with other professionals and therapists, such as social workers, occupational therapists, physiotherapist and speech and language therapists. The involvement of health professionals will depend on the level of difficulties your child has. Numerous hospital appointments can be difficult for families to organise and keep track of. This may change as your child grows and you may find it useful to keep a record of the people involved in his/her care. Do not be afraid to ask questions and find out as much as you can about your child’s individual problems. The answers may be helpful in making decisions about your child’s current and future needs. Every child is an individual and although he/she is likely to share some of the features of ACC with other affected children he/she will still have their own unique personality and developmental path. It is not possible to predict exactly what will happen to a child as they grow up or what level of care they will require, although the health professionals involved in your child’s care will be able to give you more advice and support about this issue. For many parents it is a matter of ‘wait and see’. School Children who have a diagnosis before they start school will already be involved with a Paediatrician and possibly a Child Development Team. Your paediatrician will know whether your child is likely to need any extra support when they start school and, with your permission, will inform the Education Department so they can gather information from everyone involved with your child and make sure they have the right support from the very beginning of their school life. Some children will have already started at school by the time the diagnosis is made and you may or may not be aware of difficulties they are experiencing. You may find it useful to arrange to talk to your child’s teachers to explain the changes that have been found and discuss your child’s progress in more detail. It is unlikely that any of your child’s teachers will have heard of callosal abnormalities or had experience of dealing with children with the condition so your Paediatrician will be able to give you some information to show to the school. Your child may require extra help at school and it is best to talk to your child’s teachers and the SENCO (Special Educational Needs Coordinator – each school has a teacher who has had additional training with children who need support) about what help they may need and how this may be provided. Your child’s school may be able to assess this and provide the support, or they may feel your child needs a deeper assessment of their strengths and weaknesses by an Educational Psychologist. As children get older some of the social and communication problems associated with ACC can become more obvious (see section on effects of ACC). It may be helpful to talk to your child’s teacher about this. Although we cannot change the brain malformation itself many of the challenges faced by an individual with ACC are amenable to appropriate help and intervention. Speech and Language Therapists and Psychologists may be able to help your child in these areas. It is important that, where possible, you talk to your child openly about issues as they come up and develop strategies together to deal with them. Adults Occasionally a callosal abnormality can be found as an incidental finding on a scan done for another reason, such as a head injury. In others, development of other problems such as seizures may prompt further investigations like a brain scan. For a person diagnosed in late adolescence or adulthood the diagnosis can come as a considerable shock as they are often unaware that there has been any change in the way their brain has formed. For some individuals it can feel like an explanation for difficulties they have experienced throughout their life. It may be useful to talk to a neurologist about the changes on a scan in more detail. If this has been an incidental finding and you are otherwise well there are often no regular medical checks that need to be arranged. As the findings on the brain scan will not change it is unlikely that this will affect your health in new or unexpected ways. You may find it useful to talk to a clinical geneticist if there have been any other unexplained developmental problems or there are concerns about other members of your family.

ACC is diagnosed by performing a scan of the brain. For many individuals a scan will be done during childhood because of problems identified with their development, seizures or other problems. One or more of three methods are commonly used (see glossary of terms section for details). At the moment there is no other test that can reliably diagnose the presence of ACC in an individual. Ultrasound – pre- or post-natal CT MRI – pre- or post-natal

FAQs Archive - Page 2 of 3 - Welcome to Corpal

Q: Agenesis of the corpus callosum: genetic, developmental and functional aspects of connectivity

Title: Agenesis of the corpus callosum: genetic, developmental and functional aspects of connectivity Authors: Paul, L.K., Brown, W.S, Adolphs, R., Tyszka, J.M., Richards, L.J., Mukherjee, P., Sherr, E.H. Journal: Nature Reviews Neuroscience, 8, 287-299. Published: 2007 This paper provides a comprehensive review of the research into ACC that has been done to date. The way the corpus callosum develops is described; this involves a complex series of multiple steps, where disruption at any stage can lead to ACC. A review of genetic factors that cause ACC is provided along with possible environmental factors. The authors conclude that most cases of ACC do not have a known cause at this time. The wide-ranging consequence of ACC on behaviour and cognition is discussed. It is suggested that by grouping together individuals with similar brain anatomy we may be more successful at determining outcome. Individuals with primary ACC and good general cognitive ability often show a pattern of deficits in problem solving, social skills, processing emotion, and in the practical use of language and communication. These difficulties may be due to problems transferring information between hemispheres or to other abnormalities in the brain. Many neurodevelopmental and psychiatric conditions have been linked to corpus callosum malformation or malfunctioning, including schizophrenia, autism and attention deficit hyperactivity disorder. The study of ACC may therefore provide insight on how altered brain connectivity may contribute to these disorders, as well as how information is transferred in the typically developing brain.

Q: Agenesis of the corpus callosum: prenatal diagnosis and prognosis

Title: Agenesis of the corpus callosum: prenatal diagnosis and prognosis Authors: Moutard., M., Kieffer, V., Feingold, J., Kieffer, F., Lewin, F., Adamsbaum., C., Gelot, A., Campistal I Plana, J., van Bogaert, P., Andre, M., Ponst, G. Journal: Child’s Nervous System, 19, 471-476 Published: 2003 This French study reports on the long-term outcome of children diagnosed with isolated ACC before they were born. A group of 17 children were assessed at ages 2, 4, and 6, although the drop-off rate was high and only seven children were seen at 6 years of age. Most children showed good outcome, with motor skills developing at the expected ages. Intellectual ability was generally within the normal range, although scores varied over time for some children. When the children were of school age subtle cognitive and behaviour problems emerged, particularly in reasoning, slowness, and paying attention. Outcome was not related to whether the child had complete or partial ACC, was male or female, or experienced febrile seizures.

Q: Neurodevelopmental outcome in prenatally diagnosed isolated agenesis of the corpus callosum

Title: Neurodevelopmental outcome in prenatally diagnosed isolated agenesis of the corpus callosum Authors: Chadie, A., Radi, S., Trestard, L., Charollais, A., Eurin, D., Verspyck, E., Marret, S. Journal: Acta Paediatrica, 97, 420-424 Published: 2008 This French study looked at the outcome of 20 children who were diagnosed with isolated ACC before they were born. Children were generally younger than 6 years when assessed, but ranged between 3 and 16 years. Neurodevelopmental outcome, as defined by general intelligence, motor and cognitive abilities, was considered to be normal in 11 children (55%), which included eight with complete ACC. Five children (25%) were considered to have moderate disabilities (speech delay, comprehension difficulties, attention disorders), and four children (20%) had severe disabilities (intellectual disability, speech impairments, cerebral palsy). In three of the four severely disabled children, a follow-up MRI scan showed additional major cerebral abnormalities that were not detected in their prenatal scan.

Q: Social and behavioral problems of children with agenesis of the corpus callosum

Title: Social and behavioral problems of children with agenesis of the corpus callosum Authors: Badaruddin, D., Andrews, G., Bolte, S., Schilmoeller, K., Paul, L.K., Brown, W.S. Journal: Child Psychiatry and Human Development, 38, 287-302. Published: 2007 The researchers summarise the range of behaviour problems in children with ACC who are relatively high functioning and typically developing (i.e., no reported delays in early motor milestones of sitting and walking) as reported by a parental questionnaire (the Child Behavior Checklist). Parents of 33 children with ACC (aged 6 to 11 years) reported considerable problems in areas of attention (e.g., daydreaming, staring, being confused, inability to sit still, failing to finish tasks, wandering away), unusual thoughts, social interactions, physical complaints and aggressive behaviour. Fewer problems were reported by parents of 28 younger children with ACC (aged 2 to 5 years), with sleep difficulties being the primary problem reported. Some children with ACC had traits that related to diagnosis of autism; for example difficulties initiating and sustaining conversation, establishing friendships, showing social and emotional give-and-take, using and understanding nonverbal communication. The typical repetitive and restricted behaviours seen in autism were not so apparent in children with ACC.