The importance of conducting qualitative research in rare genetic syndromes: My experiences of the MYT1L-syndrome and SOX11-syndrome interview study

 

MYT1L-syndrome (or 2p25.3 deletion syndrome) and SOX11-syndrome (or 2p25.2 deletion syndrome) are both newly discovered syndromes that are associated with a variety of symptoms, including intellectual disability and microcephaly (Blanchet et al., 2017; Hempel et al., 2016). Despite this, we know little about the impact that these syndromes have on the individual and their caregivers. Therefore, the first piece of research we decided to undertake as part of my PhD was a qualitative research project exploring the lived experience of the parents and caregivers of individuals with MYT1L- and SOX11- syndromes. This includes asking about relationships with the health service and education and exploring other aspects of life including the impact that the syndromes have on work, finance, and amongst others, the impact on family and social networks.

 

Studies like this one will enable caregivers to voice their opinions on what is important to them and how the syndromes impact their lives on a daily basis. This will allow us to develop an understanding of which elements of the syndromes impact life the most and will hopefully lead to the development of interventions that make life easier to manage, thus increasing quality of life.

 

Qualitative research has previously been utilised to understand the lived experience of these populations in other rare genetic syndromes. Whilst this research does not explore MYT1L- and SOX11-syndromes specifically, a wide range of literature exists that has successfully undertaken qualitative research in rare genetic diseases, which includes Rett Syndrome, Duchenne Muscular Dystrophy and Huntington’s Disease (Bendixen & Houtrow, 2017; Palacios-Ceña et al., 2019; Pelentsov et al., 2016), and multiple themes have been explored and resulted in meaningful interventions or educational opportunities in a plethora of sectors

 

Although the MYT1L- and SOX11- interview study is still ongoing, the interviews so far have demonstrated to me why speaking directly with parents and caregivers is so important in extending our understanding of rare genetic syndromes. Caregivers provide a unique perspective and are able to share the experiences that are often detrimental including cognitive and behavioural problems, but also shine a light on the positives experienced, including the ability to spend quality family time together and participate, to a large extent, in the activities a neurotypical family would do.

 

One of my biggest learnings so far is that whilst those in academia are not yet, and may never be, experts in these syndromes, experts do already exist - the caregivers. As academics we should seek to include them in our research and learn from them and we should feel a huge sense of privilege whilst doing so. Other types of research are, without a doubt, fundamental to extending our knowledge and understanding of these syndromes. However, qualitative research provides a unique insight into a much richer and fuller insight into what life really looks like for individuals with rare genetic syndromes and their families and the findings highlights avenues for meaningful future research.

 

Parents or caregivers of an individual with MYT1L-syndrome (or 2p25.3 deletion syndrome) or SOX11-syndrome (or 2p25.2 deletion syndrome) can take part in this study remotely. Participating in this study would involve a 60-minute video call exploring various aspects of life, including the impact of the syndrome on education and healthcare. If you would like to find out more about the study or if you would like to sign up to take part, complete our contact form or email lsstokes1@sheffield.ac.uk.

 

Louis Stokes

PhD candidate (SiTRAN)

References

Bendixen, R.M. and Houtrow, A., 2017. Parental reflections on the diagnostic process for  Duchenne muscular dystrophy: a qualitative study. Journal of Pediatric Health Care, 31(3), pp.285-292.

 

Blanchet, P., Bebin, M., Bruet, S., Cooper, G.M., Thompson, M.L., Duban-Bedu, B., Gerard, B.,     Piton, A., Suckno, S., Deshpande, C. and Clowes, V., 2017. MYT1L mutations cause      intellectual disability and variable obesity by dysregulating gene expression and               development of the neuroendocrine hypothalamus. PLoS genetics, 13(8),              p.e1006957.

 

Hempel, A., Pagnamenta, A.T., Blyth, M., Mansour, S., McConnell, V., Kou, I., Ikegawa, S.,      Tsurusaki, Y., Matsumoto, N., Lo-Castro, A. and Plessis, G., 2016. Deletions and de      novo     mutations of SOX11 are associated with a neurodevelopmental disorder with             features of Coffin–Siris syndrome. Journal of medical genetics, 53(3), pp.152-162.

 

Palacios-Ceña, D., Famoso-Pérez, P., Salom-Moreno, J., Carrasco-Garrido, P., Pérez-Corrales,     J., Paras-Bravo, P. and Güeita-Rodriguez, J., 2019. “Living an Obstacle Course”: A Qualitative Study Examining the Experiences of Caregivers of Children with Rett               Syndrome. International journal of environmental research and public health, 16(1),  p.41.

 

Pelentsov, L.J., Fielder, A.L. and Esterman, A.J., 2016. The supportive care needs of parents with a child with a rare disease: a qualitative descriptive study. Journal of Pediatric              Nursing, 31(3), pp.e207-e218.

 

Brain Activity Research in Rare Genetic Disorders

 

Investigating the brain activity of people with rare genetic syndromes is important to help advance our knowledge and understanding of these syndromes. Neuroimaging tools, such as EEG (electroencephalography), can be used to non-invasively detect brain activity. Sensors are placed on the scalp to record the electrical signals arising from populations of brain cells communicating and oscillating in synchrony. The dynamic nature of brain processes means that different patterns of brain activity can always be observed whether due to external stimuli, such as hearing a sound, or due to internal processes, such as recalling a memory.

In a clinical setting, EEG has been typically used to detect and diagnose seizures/ epilepsy disorders. In research, EEG, in combination with advanced signal analysis techniques, has been used to examine the observed brain activity patterns in clinical groups in comparison to a reference (typically-developing) group. EEG research also focuses on subtle differences in brain activity that can be detected due to advanced analysis techniques. Because these studies tend to be conducted on a group level, EEG research on rare genetic syndromes has been very limited due to the challenge of identifying large numbers of participants with a particular rare genetic syndrome. However, this is rapidly changing due to the recognition of the importance of secure open-data and collaborative practices among research groups, charities, and other entities.

At ShARL, we have studied the brain activity of individuals with 16p11.2 deletions and duplications. 16p11.2 deletion refers to the rare event of having a missing segment of DNA in the ‘16p11.2’ region (i.e., short arm of chromosome 16, segment ’11.2’); and 16p11.2 duplication refers to having an extra portion of DNA at the ‘16p11.2’ region. Individuals with 16p11.2 deletions and duplications are at an increased risk of intellectual disability, developmental delays, psychiatric symptoms and other symptoms and difficulties. Prior to conducting our study, we surveyed the available resources and databases that have the permission to share anonymised EEG data of rare genetic or autism-related syndromes to approved bona fide researchers. This step is valuable as it enables studies of rare populations that otherwise would have been difficult to achieve and allows for the primary and/or further analysis of previously collected datasets by various lab groups. For our studies, we have obtained approval from the Simons Foundation Autism Research Initiative (SFARI) to analyse data previously collected by SFARI collaborators. The results showed altered brain activity at resting-state (i.e., while participants are resting) and in response to visual stimuli (i.e., when participants are viewing alternating black and white checkerboards on a computer screen) in 16p11.2 deletion and duplication carriers. The observed brain activity in the frontal and back regions of the brain was atypical in various indices of brain cell communication and function. Importantly, we have also found that certain brain activity indices were associated with increased severity of pervasive developmental problems and anxiety problems. Our study was the first to provide evidence that resting-state brain activity is altered in 16p11.2 deletion and duplication carriers and that this may be linked with the developmental and psychiatric problems observed in this population. Although challenging, EEG brain research aims to further our understanding of the specific brain alterations found in rare genetic syndromes - and how these changes in brain activity may contribute to certain symptoms. Findings from this line of research could also produce reliable intermediate indicators of prognosis and treatment progression in these syndromes. 

 Dr Reem (Eema) Al-Jawahiri

Post-doctoral research associate

 

 

 

References:

 

Al-Jawahiri R., Jones M., Milne E. (in press). Spontaneous neural activity relates to psychiatric traits in 16p11.2 deletion carriers: an analysis of EEG spectral power and multi-scale entropy. Journal of Psychiatric Research. https://doi.org/10.1016/j.jpsychires.2020.10.036

Al-Jawahiri R., Jones M., Milne E. (2019). Atypical neural variability in carriers of 16p11.2 copy number variants. Autism Research. https://doi.org/10.1002/aur.2166

The simons vip consortium. (2012). Simons Variation in Individuals Project (Simons VIP): A Genetics- First Approach to Studying Autism Spectrum and Related Neurodevelopmental Disorders. Neuron, 73(6), 1063-1067. https://doi.org/10.1016/j.neuron.2012.02.014