EC Neurology

Myotonic Dystrophy Type 1 (DM1), a rare autosomal dominant disorder caused by a CTG triplet repeat expansion in the DMPK gene, manifests with diverse physical, cognitive, and behavioral symptoms. While its neuromuscular features are well-documented, cognitive and behavioral aspects remain underexplored. This study piloted a neuropsychological test battery for children with DM1, assessing its feasibility and sensitivity in eight participants (ages 11-19) from the Neuromuscular Reference Center at University Hospitals Leuven.

The test battery evaluated intelligence, memory, visual-motor integration, and executive functions, supplemented by parent, teacher, and self-report questionnaires measuring behavior and executive functioning. Results showed 75% of participants scored below average on intelligence tests, with total IQ negatively correlated with CTG repeat size (ρ = -0.69, p < .05). Distinct memory patterns emerged: visual memory deficits correlated negatively with CTG repeat size (ρ = -0.76, p < .05), while verbal memory showed a positive correlation (ρ = 0.74, p < .05). Behavioral assessments revealed significant deficits in attention (75%, p < .001), working memory (71.5%, p < .01), and initiative-taking (p < .01).

The findings underscore the utility of this battery in identifying DM1-associated cognitive and behavioral deficits and suggest distinct neural pathways for visual and verbal memory processing. These results highlight the need for more neuropsychological and imaging studies to better understand the neural mechanisms underlying DM1.

 Keywords: Cognitive and Behavioral Deficits; Myotonic Dystrophy Type 1 (DM1); CTG Triplet Repeat; DMPK Gene; Children

1. Darin N and Tulinius M. “Neuromuscular disorders in childhood: a descriptive epidemiological study from western Sweden”. Neuromuscular Disorders 1 (2000): 1-9.
2. Douniol M., et al. “Psychiatric and cognitive phenotype of childhood myotonic dystrophy type 1”. Developmental Medicine and Child Neurology10 (2012): 905-911.
3. Douniol M., et al. “Psychiatric and cognitive phenotype in children and adolescents with myotonic dystrophy”. European Child and Adolescent Psychiatry 12 (2009): 705-715.
4. Lagrue E., et al. “A large multicenter study of pediatric myotonic dystrophy type 1 for evidence-based management”. Neurology8 (2019): e852-e865.
5. Angeard N. “A neurodevelopmental approach to myotonic dystrophy type 1”. Developmental Medicine and Child Neurology 10 (2019): 1126.
6. Sweere DJJ., et al. “Cognitive phenotype of childhood myotonic dystrophy type 1: A multicenter pooled analysis”. Muscle Nerve1 (2023): 57-64.
7. Peglar LM., et al. “White matter lesions detected by magnetic resonance imaging in neonates and children with congenital myotonic dystrophy”. Pediatric Neurology 96 (2019): 64-69.
8. Ho G., et al. “Myotonic dystrophy type 1: clinical manifestations in children and adolescents”. Archives of Disease in Childhood 1 (2019): 48-52.
9. Goossens E., et al. “Emotional and behavioral profile and child psychiatric diagnosis in the childhood type of myotonic dystrophy”. Genetic Counseling 4 (2000): 317-327.
10. Steyaert J., et al. “A study of the cognitive and psychological profile in 16 children with congenital or juvenile myotonic dystrophy”. Clinical Genetics 3 (1997): 135-141.
11. Echenne B., et al. “Myotonic dystrophy type I in childhood Long-term evolution in patients surviving the neonatal period”. European Journal of Paediatric Neurology 3 (2008): 210-223.
12. Antonini G., et al. “Health-related quality of life in myotonic dystrophy type 1 and its relationship with cognitive and emotional functioning”. Journal of Rehabilitation Medicine 3 (2006): 181-185.
13. Ashizawa T., et al. “Consensus-based care recommendations for adults with myotonic dystrophy type 1”. Neurology Clinical Practice 6 (2018): 507-520.
14. Minnerop M., et al. “Current progress in CNS imaging of myotonic dystrophy”. Frontiers in Neurology 9 (2018): 646.
15. Angelini C and Pinzan E. “Advances in imaging of brain abnormalities in neuromuscular disease”. Therapeutic Advances in Neurological Disorders 12 (2019): 1756286419845567.
16. Angeard N., et al. “A new window on neurocognitive dysfunction in the childhood form of myotonic dystrophy type 1 (DM1)”. Neuromuscular Disorders7 (2011): 468-476.
17. Zalonis I., et al. “Toward understanding cognitive impairment in patients with myotonic dystrophy type 1”. Archives of Clinical Neuropsychology 4 (2010): 303-313.
18. Kledzik AM and Dunn DW. “The importance of screening for internalizing symptoms, inattention, and cognitive difficulties in childhood-onset myotonic dystrophy”. Developmental Medicine and Child Neurology 10 (2012): 874-875.
19. Wozniak JR., et al. “White matter abnormalities and neurocognitive correlates in children and adolescents with myotonic dystrophy type 1: a diffusion tensor imaging study”. Neuromuscular Disorders 2 (2011): 89-96.
20. Ekström AB., et al. “Autism spectrum conditions in myotonic dystrophy type 1: a study on 57 individuals with congenital and childhood forms”. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 6 (2008): 918-926.
21. Caso F., et al. “Cognitive impairment in myotonic dystrophy type 1 is associated with white matter damage”. PLoS One8 (2014): e104697.
22. Morin A., et al. “Unravelling the impact of frontal lobe impairment for social dysfunction in myotonic dystrophy type 1”. Brain Communications 3 (2022): fcac111.
23. Johnson NE., et al. “Consensus-based care recommendations for congenital and childhood-onset myotonic dystrophy type 1”. Neurology Clinical Practice 5 (2019): 443-454.