Imagine being the parent of a child with a rare genetic disorder that affects heart, mind and brain. Then imagine that this ‘rare’ disorder in fact effects up to fifteen thousand people in the UK and Ireland, with around 200 babies being born with the disorder every year. How can such a common disorder still be under the radar?
22q11.2 Deletion Syndrome (22q11.2DS) is a chromosomal disorder. People with this syndrome are missing a portion of genetic material from region 11.2 of the long arm (q) of one of their chromosome 22.
This deletion can lead to highly variable outcomes in physical development, cognition and mental health; some individuals are mildly affected, others severely so. The majority of people with this deletion will however have heart disease from birth, problems with their immune system and malformations of their palate.
In addition, this syndrome is one the strongest known risk factors for developing schizophrenia; around 25% of people with 22q11.2DS develop schizophrenia in adulthood. Children with this syndrome also have high rates of attention-deficit hyperactivity disorder (ADHD), anxiety disorders, autism spectrum disorder (ASD) and oppositional defiant disorder.
In addition to these outcomes, a preliminary body of research suggests that people with 22q11.2DS may be at risk of epilepsy. A recent study found that this deletion was more common in people with epilepsy than in people without. Other studies have taken the opposite approach and have examined the rate of epilepsy in people with 22q11.2DS. They have found that up to 15% of people with 22q11.2DS have epilepsy, compared with 1% in the general population.
This research has its limitations however. The majority of studies exploring epilepsy in 22q11.2DS involved reviewing medical records. This approach is useful for identifying people with epilepsy who have accessed clinical services, but may fail to detect those people with epilepsy who haven’t, perhaps due to living in a socioeconomically deprived area or because they and their family do not realise that they are having seizures. This is typically the case for more ‘minor’, non-convulsive seizures; for example, absence seizures, which are very brief interruptions of consciousness where the person appears vacant. Therefore, we suspect that the epilepsy prevalence in 22q11.2DS is under-represented in these studies.
In addition, very little research has been conducted into the associations of epilepsy with cognition and mental health in people with 22q11.2DS. There is evidence to suggest that people with 22q11.2DS who have seizures shortly after birth go on to have poorer intellectual ability. More research needs to be conducted however in order to fully understand the impact seizures have on various areas of development in 22q11.2DS.
It is important that we know how prevalent epilepsy is in this syndrome and the impact that seizures have on development. This is because in the general population epilepsy is known to be associated with poor outcomes: intellectual disability and psychiatric disorders such as depression, anxiety and ASD are more common in people with epilepsy.
My PhD project aims to systematically assess whether a group of children and adolescents with 22q11.2DS have had seizures, or meet criteria for an epilepsy diagnosis. I’m also interested in the impact that seizures have on their brain activity, cognition and mental health.
So far, I’ve given a screening questionnaire to parents of young people with 22q11.2DS that asks about whether their child has had an epilepsy diagnosis, seizures and symptoms which could possibly reflect unrecognised seizures (e.g. “Does your child daydream or stare into space more than other children?”). Whilst 7% of children with 22q11.2DS have had an epilepsy diagnosis, 55% screened positive on at least one item of the questionnaire.
I also looked at whether children who screened positive on the epilepsy questionnaire had differences in their development, compared to those that screened negative. I found that positive screens were more likely to have a higher number of psychiatric diagnoses, behaviours indicative of ASD, motor-coordination problems and anxiety symptoms (data on mental health and motor problems were collected as part of the ongoing Experiences of CHildren with cOpy Number Variants [ECHO] study
These findings suggest that young people with 22q11.2DS have high rates of seizure-related events and that these events have a detrimental impact on motor coordination and psychiatric health. However, we need to confirm whether these events that parents have told us about in the epilepsy questionnaire are epileptic seizures, as opposed to representing some other aspect of 22q11.2DS. For example, saying your child daydreams or stares into space more than other children could be telling us about an ADHD-related behaviour.
In order to do this, I am currently following up those young people with 22q11.2DS who have screened positive on my questionnaire with a detailed seizure assessment. I visit them in their home and record the electrical activity of their brain over a 24-hour period, a technique known as electroencephalography (EEG). By doing this, I may be able to detect abnormal changes in brain activity that can support an epilepsy diagnosis. I’m also collecting interview, video and medical-record data about the events parents have told us about, which will help the neurologists I’m working with to decide whether it is an epileptic seizure. To get an idea of how often the event occurs, I’m asking parents to keep a diary over a two-month period.
My research may have numerous clinical implications. By highlighting the prevalence and recognising the types of seizures and epilepsy in 22q11.2DS and their impact on development, clinicians may closely monitor young people with 22q11.2DS from early on in life for seizures. This could lead to earlier treatment for seizures and ultimately better outcomes for these young people.
Young people with 22q11.2DS have many challenges to overcome. By clearly identifying the various consequences of the deletion, we can develop treatments and interventions that can help these young people better overcome these challenges. I hope that my research can help to shed light on epilepsy in 22q11.2DS and contribute to improving the lives of young people with this syndrome.