Faculty Mentor: Melissa Dixon (Human Genetics, University of Utah)

Background

Congenital myotonic dystrophy (CDM) is a severe, multisystemic neuromuscular disorder frequently associated with cognitive and developmental impairments (Hageman et al., 1993; Harper, 2001). Recent studies suggest elevated autism spectrum disorder (ASD) traits in CDM, especially among children with comorbid intellectual disability (ID) (Angeard et al., 2017; Ekström et al., 2008; Douniol et al., 2008; Douniol et al., 2012). However, specific predictors of ASD traits and behavioral profiles linked to ID in CDM are not well understood.

Objective

To characterize specific autism-related traits (i.e., social communication difficulties, restricted and repetitive behaviors, sensory sensitivities, daily living skills deficits, and behavioral dysregulation) in children with CDM and to examine their associations with intellectual functioning and other clinical characteristics.

Methods

Thirty-two children (ages 3-13) with genetically confirmed CDM enrolled in a natural history study were assessed. Following informed consent, participants completed medical and neurological evaluations, physical function testing, and neuropsychological assessment. Intelligence was assessed using standardized cognitive tests (Wechsler 2003; Wechsler 2002); adaptive functioning was evaluated using the caregiver-report (Sparrow et al., 2005). Autism traits were assessed with three standardized proxy measures (Ehlers et al., 1999; Bodfish et al., 2000; Rutter et al., 2003). Intellectual disability (ID) classification was determined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (APA, 2013), criteria. Group differences in autism traits were examined using independent samples t-tests. Logistic regression was used to evaluate predictors of autism screening positivity, including ID status, age, sex, CTG repeat size, and speech delay.

Results

Speech delay did not significantly predict ASD screening positivity. Intellectual disability was the strongest predictor: children with ID were over 65 times more likely to screen positive for ASD. Younger age was also associated with higher odds of ASD positivity. Children with ID exhibited significantly elevated ASD scores across all measures, particularly in social communication domains.

Conclusion

Intellectual disability, not speech delay, was the primary driver of ASD traits in CDM. These findings support the need for early, targeted neuropsychological screening and ASD-focused assessment in this high-risk population.

References

American Psychiatric Association. (2013). Diagnostic and statistical manual of mental  disorders (5th ed.). American Psychiatric Association.

Angeard, N., Huerta, E., Jacquette, A., Cohen, D., Xavier, J., Gargiulo, M., Servais, L.,
Eymard, B., & Héron, D. (2017). Childhood-onset form of myotonic dystrophy type 1 and autism spectrum disorder: Is there comorbidity? Neuromuscular Disorders, 28(3), 216–221. https://doi.org/10.1016/j.nmd.2017.12.006

Angeard, N., Jacquette, A., Gargiulo, M., Radvanyi, H., Moutier, S., Eymard, B., &  Héron, D. (2011). A new window on neurocognitive dysfunction in the childhood form of myotonic dystrophy type 1 (DM1). Neuromuscular Disorders, 21(7), 468–476. https://doi.org/10.1016/j.nmd.2011.04.009

Bodfish, J. W., Symons, F. J., Parker, D. E., & Lewis, M. H. (2000). Repetitive Behavior  Scale–Revised (RBS-R) [Database record]. APA PsycTests. https://doi.org/10.1037/t17338-000

Brook, J., McCurrach, M. E., Harley, H. G., Buckler, A. J., Church, D., Aburatani, H.,  Hunter, K., Stanton, V. P., Thirion, J., Hudson, T., Sohn, R., Zemelman, B., Snell, R. G., Rundle, S. A., Crow, S., Davies, J., Shelbourne, P., Buxton, J., Jones, C., Housman, D. E. (1992). Molecular basis of myotonic dystrophy: Expansion of a trinucleotide (CTG) repeat at the 3′ end of a transcript encoding a protein kinase family member. Cell, 68(4), 799–808. https://doi.org/10.1016/0092-8674(92)90154-5

Douniol, M., Jacquette, A., Cohen, D., Bodeau, N., Rachidi, L., Angeard, N., Cuisset, J.,
Vallée, L., Eymard, B., Plaza, M., Héron, D., & Guilé, J. (2012). Psychiatric and cognitive phenotype of childhood myotonic dystrophy type 1. Developmental Medicine & Child Neurology, 54(10), 905–911. https://doi.org/10.1111/j.1469-8749.2012.04379.x

Douniol, M., Xavier, J., Jacquette, A., Afenjar, A., Angeard, N., Heron, D., & Cohen, D.  (2007). Phénotype psychiatrique des maladies neuromusculaires de l’enfant: revue de la littérature. Neuropsychiatrie De L Enfance Et De L Adolescence, 56(2), 63–72. https://doi.org/10.1016/j.neurenf.2007.03.006

Echenne, B., & Bassez, G. (2013). Congenital and infantile myotonic dystrophy.  Handbook of Clinical Neurology, 1387–1393. https://doi.org/10.1016/b978-0-444-59565-2.00009-5

Ehlers, S., Gillberg, C. & Wing, L. (1999). A Screening Questionnaire for Asperger Syndrome and Other High-Functioning Autism Spectrum Disorders in School Age Children. J Autism Dev Disord 29, 129–141. https://doi.org/10.1023/A:1023040610384

Ekström, A., Hakenäs‐Plate, L., Samuelsson, L., Tulinius, M., & Wentz, E. (2008).  Autism spectrum conditons in myotonic dystrophy type 1: A study on 57 individuals with congenital and childhood forms. American Journal of Medical Genetics Part B Neuropsychiatric Genetics, 147B(6), 918–926. https://doi.org/10.1002/ajmg.b.30698

Ekström, A., Hakenäs‐plate, L., Tulinius, M., & Wentz, E. (2009). Cognition and adaptive skills in myotonic dystrophy type 1: a study of 55 individuals with congenital and childhood forms. Developmental Medicine & Child Neurology, 51(12), 982–990. https://doi.org/10.1111/j.1469-8749.2009.03300.x

Fu, Y. H., Pizzuti, A., Fenwick, R. G., King, J., Rajnarayan, S., Dunne, P. W., Dubel, J., Nasser, G. A., Ashizawa, T., De Jong, P., Wieringa, B., Korneluk, R., Perryman, M. B., Epstein, H. F., & Caskey, C. T. (1992). An unstable triplet repeat in a gene related to myotonic muscular dystrophy. Science, 255(5049), 1256–1258. https://doi.org/10.1126/science.1546326

Hageman, A., Gabreëls, F., Liem, K., Renkawek, K., & Boon, J. (1993). Congenital myotonic dystrophy; a report on thirteen cases and a review of the literature. Journal of the Neurological Sciences, 115(1), 95–101. https://doi.org/10.1016/0022-510x(93)90072-7

Health, D. of. (2023). IBIS-PH – Complete Health Indicator Report – Birth rates. Utah.gov. https://ibis.utah.gov/ibisph-view/indicator/complete_profile/BrthRat.html?utm_source

Hilton-Jones, D. (2002). Myotonic dystrophy, 3rd edition: major problems in neurology series, No 37: By Peter S Harper (Pp 436, pound55.00). Published by W B Saunders, London, 2001. ISBN 0 7020 2152 0. Journal of Neurology Neurosurgery & Psychiatry, 72(3), 422a–4422. https://doi.org/10.1136/jnnp.72.3.422-a

Howe, S. J., Lapidus, D., Hull, M., Yeaw, J., Stevenson, T., & Sampson, J. B. (2022a).  Healthcare resource utilization, total costs, and comorbidities among patients with myotonic dystrophy using U.S. insurance claims data from 2012 to 2019. Orphanet Journal of Rare Diseases, 17(1). https://doi.org/10.1186/s13023-022-02241-9

Howe, S. J., Lapidus, D., Hull, M., Yeaw, J., Stevenson, T., & Sampson, J. B. (2022b). Correction: Healthcare resource utilization, total costs, and comorbidities among patients with myotonic dystrophy using U.S. insurance claims data from 2012 to 2019. Orphanet Journal of Rare Diseases, 17(1). https://doi.org/10.1186/s13023-022-02401-x

Johnson, N. E., Butterfield, R. J., Mayne, K., Newcomb, T., Imburgia, C., Dunn, D.,
Duval, B., Feldkamp, M. L., & Weiss, R. B. (2021). Population-Based Prevalence of Myotonic Dystrophy Type 1 Using Genetic Analysis of Statewide Blood Screening Program. Neurology, 96(7), e1045–e1053. https://doi.org/10.1212/WNL.0000000000011425

Lord C, Luyster RJ, Gotham K, Guthrie W. (2012). Autism Diagnostic Observation
Schedule, Second Edition (ADOS-2) Manual (Part II): Toddler Module. Torrance, CA: Western Psychological Services. Prendergast, P., Magalhaes, S., & Campbell, C. (2010). Congenital myotonic dystrophy in a national registry. Paediatrics & Child Health, 15(8), 514–518. https://doi.org/10.1093/pch/15.8.514

Rutter M, Lord C, Bailey A. (2003). The Social Communication Questionnaire (SCQ). WPS.
STATA Corp. (2020). STATA (Version 17.0, BE-Basic Edition) [Software]. STATA
Corp

Wechsler, D. (2003). Wechsler Intelligence Scale for Children—4th Edition (WISC-IV®). San Antonio, TX: Harcourt Assessment.

Wechsler, D. (2002). Wechsler Preschool and Primary Scale of Intelligence—3rd Edition
(WPPSI-III®). San Antonio, TX: Harcourt Assessment.