UCL Great Ormond Street Institute of Child Health


Great Ormond Street Institute of Child Health


Addressing gap of knowledge in neurodevelopmental and mental health difficulties in Duchenne Muscula

Supervisors: Professor Francesco Muntoni, Professor Will Mandy

Addressing gap of knowledge in neurodevelopmental and mental health difficulties in Duchenne Muscular Dystrophy

Duchenne Muscular Dystrophy (DMD) is rare genetic disease, which causes progressive muscle weakness leading to loss of ambulation in the mid-adolescent years. This disease is caused by gene deletions that stop the production of dystrophin in muscles and in the brain. The DMD gene is composed by a variety of isoforms. All mutations affect the production of dystrophin in the muscle (dystrophin muscle isoform Dp427). Unlike muscle, the brain expresses multiple different dystrophin isoforms, in addition to Dp427. These include the Dp140 and Dp71 isoforms. Depending on the site of the DMD mutations, this may have implications for the resulting central nervous system phenotype [1, 2]. 

So far, most of the research focuses on the involvement of dystrophin in muscles and the motor-related associations with the disorder however, over the years, it has become clear that DMD carries with it a significant burden in terms of neurodevelopmental and mental health difficulties. Studies have shown that brain dystrophin deficiency results in a neuropsychiatric syndrome in more than 50% of patients and have indicated higher incidence of neurobehavioral comorbidities such as Autism Spectrum Disorders (ASD), Attention Deficit Hyperactivity Disorders (ADHD), Obsessive Compulsive Disorders (OCD), Anxiety Disorders and Depressive disorders [3,4].  

This reflects a direct causal pathway, whereby genetic differences that cause DMD impact directly on the development of brain structure and function, increasing therefore the risk of developing intellectual disability and neurodevelopmental disorders [4,1]. In addition, there are likely indirect links between DMD and poor mental health, whereby the physical disabilities and life-limiting nature of the condition play out in interactions with the child's family and wider system.

Overall, the neurodevelopmental and mental health problems of DMD have significant impact on quality of life and daily functioning of children with DMD and their families and represent an obvious target for clinical intervention. However, the opportunities for good practice in this area are constrained by lack of knowledge about the nature, causes, precise effects and treatments of these emotional, behavioural and developmental difficulties.

This project would be a step towards addressing these gaps in knowledge, and would ask:

1/. What is the precise profile of neurodevelopmental and mental health difficulties in DMD, and how does this vary by age and genotype?

2/. What is the impact of these neurodevelopmental and mental health difficulties in DMD on (i) child and family quality of life; (ii) child and family functioning?

3/. What type of help do children families value for these difficulties?

4/. What do expert clinicians consider to be the current best-practice model for supporting children and families with neurodevelopmental and mental health difficulties in DMD?

The project would draw on:(i) unique databases already available within the team, charting mental health difficulties in large samples of boys with DMD; (ii) new quantitative data collected via GOSH's world-leading DMD clinic; (iii) qualitative interviews with patients and their families; (iv) a Delphi study to summarise expert consensus.


1.     Muntoni F, Torelli S, Ferlini A. Dystrophin and mutations: one gene, several proteins, multiple phenotypes. Lancet Neurol. 2003 Dec;2(12):731-40. 
2.    Daoud, F., et al., Analysis of Dp71 contribution in the severity of mental retardation through comparison of Duchenne and Becker patients differing by mutation consequences on Dp71 expression. Hum Mol Genet, 2009. 18(20): p. 3779-94.
3.    Ricotti, V., W. P. Mandy, M. Scoto, M. Pane, N. Deconinck, S. Messina, E. Mercuri, D. H. Skuse and F. Muntoni (2016). "Neurodevelopmental, emotional, and behavioural problems in Duchenne muscular dystrophy in relation to underlying dystrophin gene mutations." Developmental medicine and child neurology 58(1): 77-84
4.    Hendriksen, R., G., F., Vles, J., S., H., Aalbers, M., W., Chin, R., F., M. and Hendriksen, J., G., M. (2018).  Brain-related comorbidities in boys and men with Duchenne Muscular Dystrophy: A descriptive study. Eur J Paediatr Neurol, 22(3): p. 488-497.