What is Agenesis of the Corpus Callosum?
Agenesis of the Corpus Callosum (ACC) is a rare neurological condition in which the Corpus Callosum, the major “pathway“ for information which links the two hemispheres of the brain, fails to develop fully. The condition is usually diagnosed by CT (Computer Tomographic) or MRI (Magnetic Resonance Imaging) scan.
The effects of the condition are variable; ranging from normal development (where the condition may be undetected or be revealed incidentally), through mild developmental delay to severe learning difficulties, epilepsy, visual impairment and delayed motor development. There may be other brain malformations present, for example microcephaly (small brain) or hydrocephalus (obstruction of the flow of fluid in the head).
The corpus callosum is the largest bundle of connections between the right and the left sides (hemispheres) of the brain. It is often described as a “bridge” that enables communication between the two halves of the brain.
In humans, the corpus callosum is made of millions of nerve fibres (over 190 million). In early pregnancy, many systems are involved in guiding corpus callosum fibres to connect the hemispheres. The first corpus callosum axons cross from one side to the other around 13-14 weeks post conception and the entire length of the callosum is complete by week 20.
Soon after birth the nerve fibres become covered with an insulating coat (made of myelin), which helps information travel faster along the axons. The myelin coat starts to form within the first year of life and makes the corpus callosum expand in size further until its shape resembles that of an adult. There is also some fine-tuning of the connections between nerve fibres, where new connections form and other connections are removed.
Our brains, and therefore our corpus callosum, continue to grow during childhood and adolescence as they become more effective and efficient. The eventual size and shape of a normal corpus callosum can vary between individuals.
The human brain has several, much smaller, bundles of nerve fibres that connect the right and left hemispheres, such as, the anterior, posterior and hippocampal commissures.
The formation of the corpus callosum is a complex process and a large number of interacting genes are involved in its development during pregnancy. As a consequence, there can be many different reasons behind why the formation becomes disrupted in some way. Some of these causes can be identified – but for many individuals, the reason for the disruption remains unknown.
Known causes of disruption in the normal development of the corpus callosum include:
• Genetic or chromosomal changes: a faulty gene may have prevented the neural circuits in the brain forming properly. Some genetic disorders may be passed on from parent to child, but most develop as a sporadic genetic fault that just happens.
• Viral infections: an infection or virus in the womb (e.g., rubella) may have interfered with the developing brain during pregnancy; often such infections are completely silent and the mother would not have been aware of them.
• Exposure to certain toxins or medications: exposure to certain drugs or excess alcohol can increase the risk of a child being born with a callosal disorder.
• Disruptions to normal brain development: such as the development of a cyst that may have blocked the growth of the corpus callosum.
Will it be possible to identify the cause?
All of the tests done by health professionals both before and after diagnosis of agenesis of the corpus callosum aim to find clues to the underlying cause of the problem. In many cases doctors may not be able to find the exact cause for the condition; however, over time new clues to a diagnosis may surface as new tests are developed. It can therefore be useful to stay in touch with the health professionals involved in your child’s care in case any new developments are applicable to your family.
Reported figures in the medical literature vary widely. The most recent large scale study from the US in 2008 estimated an annual incidence of 1.8 per 10,000 babies born. The incidence in boys and girls are approximately the same, although the underlying causes for either sex may not be. It is widely acknowledged that callosal abnormalities are more common in individuals with learning and developmental disabilities.
The number of corpus callosum fibres will not increase substantially after the fetus reaches 20 weeks. Callosum fibres that are present at that point will continue to develop throughout childhood and adolescence (e.g., become myelinated). However as the rest of the brain continues to grow and develop during childhood, adolescence and even as an adult, the effects of a malformed corpus callosum may become more obvious.
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
- MRI – pre- or post-natal
(Note from the Corpal committee) Have you just been told that your baby has agenesis of the corpus callosum? This is a diagnosis you may have never heard of and your thoughts run wild, not knowing which way to turn. If you are told by a doctor that your baby has an abnormality of the brain, you might think the worst. If you need to chat with someone to see what support there is out there please email (firstname.lastname@example.org ). Please include your name and contact details and someone will get back to you as soon as possible. Or, if you prefer to be contacted by email, that’s fine too.
Please be aware that members of Corpal are not medically trained, but often will have had experience of living with a child or adult with agenesis of the corpus callosum.
For many families in the UK a callosal abnormality is picked up on routine ultrasound scanning during pregnancy at around 20 weeks. It can be difficult to know how to handle such an unexpected result like this and it is important to get as much information as you feel is necessary to make decisions about your family’s future. Your obstetrician will be able to give you more information about what the scan shows. In some cases they may suggest having a MRI scan during the pregnancy to look at the baby’s brain in more detail.
The corpus callosum is most reliably seen on ultrasound scan from 20 weeks of pregnancy onwards. At this point the brain has not fully developed and it can be very difficult to assess whether there are any changes in the corpus callosum or other brain structures. As the pregnancy progresses the brain develops further and more detail can be seen. A MRI scan may be useful in some circumstances but how much information this, or an ultrasound, can provide will depend on at what stage of pregnancy it is performed.
For a small number of families in whom a diagnosis has been made in an affected individual with a genetic test there may be the option of having a test during a pregnancy to see if the foetus is affected. If this is the case then it is useful to discuss the issues surrounding prenatal testing and its risks if possible before embarking on a pregnancy. For many families diagnosis in pregnancy relies on ultrasound and/or MRI scanning. In either case your local obstetrician or clinical genetics department will be able to discuss this with you in more detail.
Detailed investigation of a person with ACC may find a known cause for the disorder. Where ACC is thought to have occurred as the result of an infection or exposure to a medication, drug or excess alcohol, the risks of it recurring is reduced if the same exposure does not occur in the next pregnancy.
Sometimes a known syndrome is suspected by the presence of other problems such as a cleft lip or differences in how fingers have developed. Syndromes including ACC as a feature can be inherited through families or occur for the first time in an affected person. For individuals in whom a genetic or chromosomal cause is suspected there are a growing number of tests to look for changes in their genes or chromosomes. These are not currently available for all conditions. Your paediatrician or geneticist will be able to advise you further on this.
For the majority of families we are currently unable to say for certain how ACC has happened in an individual and how likely it is to happen again. For Aicardi syndrome the change is thought to occur in a gene on the X chromosome. Studies of many families with Aicardi syndrome indicate that the recurrence risk is very low.
Many individuals with ACC will also have other changes on their brain scans, such as malformations of the cerebellum, and/or problems in other parts of the body such as the eyes, skin and heart. Not only are these important to identify and treat where necessary, they can also be important clues to the underlying diagnosis. For example, girls with very specific changes on detailed eye examination (called chorioretinal lacunae) in association with brain development abnormalities may have a diagnosis of Aicardi syndrome.
The features below are based on observations of a number of individuals with ACC of varying intellectual level. Therefore this information may not be applicable to everyone. The problems that family, friends or teachers notice can change or become more apparent later in childhood. The presence of seizures or other changes in the brain structure, such as cysts or cerebellar abnormalities, may alter an individual’s abilities. If an individual has a specific diagnosis, such as Aicardi syndrome, then it may be more appropriate to look at the characteristics of other individuals with the same condition.
- Delay in achieving motor, language, and cognitive milestones
- Poor motor coordination (movement e.g. walking or throwing a ball)
- Increased sensitivity to stimulation such as food textures and touch
- High tolerance to pain
- Difficulty with complex tasks, such as using language in social situations, complex reasoning, creativity, and problem solving
- Limited sophistication of humour
- Difficulty imagining the potential consequences of behaviour
- Immature play for age
- Problems in social situations such as making inappropriate comments
- A lack of awareness of the thoughts and feelings of others
- Difficulty starting conversations and keeping conversation flowing
- Difficulty identifying what a speaker is feeling from their tone of voice or facial expressions
- Difficulty distinguishing between lies and sarcasm
- Difficulty in relationships with others, such as emotional give and take
- Limited insight into their own behaviour
A number of children with corpus callosum abnormalities will have a diagnosis of autistic spectrum disorder or Asperger’s syndrome. Some children who have problems with motor coordination may be diagnosed with dyspraxia.
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.
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’.
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.
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.
As problems with the development of the corpus callosum happen early in pregnancy it is not possible to change this. At this point we have no medical treatments which can increase the size or the function of the corpus callosum. However, like many children and adults with specific physical or learning difficulties, those with ACC are likely to benefit from a variety of interventions and specialist help at home and at school.
Information kindly collated and submitted by Dr Mary O’Driscoll, Specialist Registrar in Clinical Genetics,
St Mary’s Hospital, Manchester – October 2008