Hostname: page-component-848d4c4894-8bljj Total loading time: 0 Render date: 2024-06-26T18:30:44.606Z Has data issue: false hasContentIssue false
  • English
  • Français

Executive Functioning in the Dystrophinopathies and the Relation to Underlying Mutation Position

Published online by Cambridge University Press:  04 December 2018

Robert J. Fee ,
Jacqueline Montes  and
Veronica J. Hinton
Robert J. Fee
Affiliation:
The Graduate Center, City University of New York, Queens College, Queens, New York Gertrude H. Sergievsky Center, Columbia University, New York, New York
Jacqueline Montes
Affiliation:
Departments of Rehabilitation and Regenerative Medicine and Neurology, Columbia University, New York, New York
Veronica J. Hinton*
Affiliation:
The Graduate Center, City University of New York, Queens College, Queens, New York Gertrude H. Sergievsky Center and Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York
*
Correspondence and reprint requests to: Veronica J. Hinton, Sergievsky Center, Columbia University, 630 West 168th Street, P&S Box 16, New York, NY 10032. E-mail: vjh9@columbia.edu
Get access Rights & Permissions [Opens in a new window]

Abstract

Objectives: The aim of this study was to investigate executive skills in children with dystrophinopathy and to examine the association between executive functions and dystrophin gene mutation position. Methods: Fifty boys with dystrophinopathy (mean age, 11 years 0 months; ages range, 5 to 17 years) completed measures of intellectual functioning (IF), working memory and executive functioning [including Digit Span (working memory) and measures from the NIH Toolbox (selective attention/inhibitory control, set shifting, working memory, and processing speed)]. Parents completed the Behavior Rating Inventory of Executive Function (BRIEF). Mutation positions were categorized into three groups (upstream exon 30, 31–62, and downstream exon 63). Paired-samples t tests compared performance on executive measures to IF, and a one-way (three-group) multivariate analysis of covariance compared cognitive performance with mutation location controlling for motor functioning. Results: Mean performance on all executive measures was significantly lower than IF. Parents were also more likely to rate their child with dystrophinopathy as having clinically significant executive difficulties on the Shift, Emotional Control, and Behavior Regulation indices of the BRIEF. Mutation analyses resulted in small groups limiting power to detect subtle differences. Those with a downstream mutation position had significantly poorer performance on IF and Total Digit Span, but not on other measures of executive function including behavior. Conclusions: Individuals with dystrophinopathy have executive skill deficits, but they are not generally associated with more distal mutations. (JINS, 2019, 25, 146–155)

Keywords

DystrophinIsoformsCognitionIntelligenceExecutive functionsMutations
Type
Regular Research
Information
Journal of the International Neuropsychological Society , Volume 25 , Issue 2 , February 2019 , pp. 146 - 155
Copyright
Copyright © The International Neuropsychological Society 2018 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Banihani, R., Smile, S., Yoon, G., Dupuis, A., Mosleh, M., Snider, A., & McAdam, L. (2015). Cognitive and neurobehavioral profile in boys with Duchenne muscular dystrophy. Journal of Child Neurology, 30(11), 1472–1482.Google Scholar
Brooke, M. H., Griggs, R. C., Mendell, J. R., Fenichel, G. M., Shumate, J. B., & Pellegrino, R. J. (1981). Clinical trial in Duchenne dystrophy. I. The design of the protocol. Muscle & Nerve, 4(3), 186–197.Google Scholar
Bushby, K., Finkel, R., Birnkrant, D. J., Case, L. E., Clemens, P. R., Cripe, L., … Constantin, C. (2010). Diagnosis and management of Duchenne muscular dystrophy, part 1: Diagnosis, and pharmacological and psychosocial management. The Lancet Neurology, 9(1), 77–93.Google Scholar
Casaletto, K., Umlauf, A., Beaumont, J., Gershon, R., Slotkin, J., Akshoomoff, N., & Heaton, R. (2015). Demographically corrected normative standards for the English version of the NIH Toolbox Cognition Battery. Journal of the International Neuropsychological Society, 21(5), 378–391.Google Scholar
Cohen, E. J., Quarta, E., Fulgenzi, G., & Minciacchi, D. (2015). Acetylcholine, GABA and neuronal networks: A working hypothesis for compensations in the dystrophic brain. Brain Research Bulletin, 110, 1–13.Google Scholar
Cotton, S. M., Voudouris, N. J., & Greenwood, K. M. (2005). Association between intellectual functioning and age in children and young adults with Duchenne muscular dystrophy: Further results from a meta-analysis. Developmental Medicine & Child Neurology, 47(4), 257–265.Google Scholar
Craig, R. J., & Olson, R. E. (1991). Relationship between Wechsler scales and Peabody Picture Vocabulary Test-Revised scores among disability applicants. Journal of Clinical Psychology, 47(3), 420–429.Google Scholar
Cyrulnik, S. E., Fee, R. J., Batchelder, A., Kiefel, J., Goldstein, E., & Hinton, V. J. (2008). Cognitive and adaptive deficits in young children with Duchenne muscular dystrophy (DMD). Journal of the International Neuropsychological Society, 14(5), 853–861.Google Scholar
Daoud, F., Angeard, N., Demerre, B., Martie, I., Benyaou, R., Leturcq, F., … Tuffery, S. (2009). Analysis of Dp71 contribution in the severity of mental retardation through comparison of Duchenne and Becker patients differing by mutation consequences on Dp71 expression. Human Molecular Genetics, 18(20), 3779–3794.Google Scholar
Donders, J., & Taneja, C. (2009). Neurobehavioral characteristics of children with Duchenne muscular dystrophy. Child Neuropsychology, 15, 295–304.Google Scholar
Duke, D. C., & Harris, M. A. (2014). Executive function, adherence, and glycemic control in adolescents with type 1 diabetes: A literature review. Current Diabetes Reports, 14(10), 1–10.Google Scholar
Dunn, L. M., & Dunn, D. M. (2007). Peabody Picture Vocabulary Test (PPVT-IV) (4th ed.). Minneapolis, MN: Pearson Assessments.Google Scholar
Gignac, G. E., & Weiss, L. G. (2015). Digit Span is (mostly) related linearly to general intelligence: Every extra bit of span counts. Psychological Assessment, 27(4), 1312.Google Scholar
Gioia, G. A., Isquith, P. K., Guy, S. C., & Kenworthy, L. (2000). Behavior rating inventory of executive function. Lutz, FL: Psychological Assessment Resources, Inc.Google Scholar
Hendriksen, J. G., & Vles, J. S. (2008). Neuropsychiatric disorders in males with duchenne muscular dystrophy: Frequency rate of attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder, and obsessive--compulsive disorder. Journal of Child Neurology, 23(5), 477–481.Google Scholar
Hinton, V. J., De Vivo, D. C., Nereo, N. E., Goldstein, E., & Stern, Y. (2001). Selective deficits in verbal working memory associated with a known genetic etiology: The neuropsychological profile of duchenne muscular dystrophy. Journal of the International Neuropsychological Society, 7(1), 45–54.Google Scholar
Hinton, V. J., DeVivo, D. C., Fee, R. J., Goldstein, E., & Stern, Y. (2004). Investigation of poor academic achievement in children with Duchenne muscular dystrophy. Learning Disabilites Research & Practice, 19, 146–154.Google Scholar
Hinton, V. J., Fee, R., Goldstein, E. M., & De Vivo, D. C. (2007). Verbal and memory skills in males with Duchenne muscular dystrophy. Developmental Medicine & Child Neurology, 49(2), 123–128.Google Scholar
Hinton, V. J., Nereo, N. E., Fee, R. J., & Cyrulnik, S. E. (2006). Social behavior problems in boys with Duchenne muscular dystrophy. Journal of Developmental and Behavioral Pediatrics, 27(6), 470–476.Google Scholar
Hurlstone, M. J., Hitch, G. J., & Baddeley, A. D. (2014). Memory for serial order across domains: An overview of the literature and directions for future research. Psychological Bulletin, 140(2), 339.Google Scholar
Leaffer, E. B., Fee, R. J., & Hinton, V. J. (2016). Digit span performance in children with dystrophinopathy: A verbal span or working memory contribution? Journal of the International Neuropsychological Society, 22(7), 777–784.Google Scholar
Lidov, H. G. (1996). Dystrophin in the nervous system. Brain Pathology, 6(1), 63–77.Google Scholar
Lue, Y. J., Lin, R. F., Chen, S. S., & Lu, Y. M. (2009). Measurement of the functional status of patients with different types of muscular dystrophy. The Kaohsiung Journal of Medical Sciences, 25(6), 325–333.Google Scholar
Mazzone, E. S., Vasco, G., Palermo, C., Bianco, F., Galluccio, C., Ricotti, V., … Mercuri, E. (2012). A critical review of functional assessment tools for upper limbs in Duchenne muscular dystrophy. Developmental Medicine and Child Neurology, 54(10), 879–885.Google Scholar
Mento, G., Tarantino, V., & Bisiacchi, P. S. (2011). The neuropsychological profile of infantile Duchenne muscular dystrophy. Clinical Neuropsychology, 25(8), 1359–1377.Google Scholar
Muntoni, F., Torelli, S., & Ferlini, A. (2003). Dystrophin and mutations: One gene, several proteins, multiple phenotypes. The Lancet Neurology, 2(12), 731–740.Google Scholar
Ricotti, V., Mandy, W. P., Scoto, M., Pane, M., Deconinck, N., Messina, S., … Muntoni, F. (2016). Neurodevelopmental, emotional, and behavioural problems in Duchenne muscular dystrophy in relation to underlying dystrophin gene mutations. Developmental Medicine & Child Neurology, 58(1), 77–84.Google Scholar
Rossen, E. A., Shearer, D. K., Penfield, R. D., & Kranzler, J. H. (2005). Validity of the comprehensive test of nonverbal intelligence (CTONI). Journal of Psychoeducational Assessment, 23(2), 161–172.Google Scholar
Strauss, E., Sherman, E. M. S., & Spreen, O. (2006). A compendium of neuropsychological tests: Administration, norms, and commentary. Oxford: Oxford University Press.Google Scholar
Taylor, P. J., Betts, G. A., Maroulis, S., Gilissen, C., Pedersen, R. L., Mowat, D. R., … Buckley, M. F. (2010). Dystrophin gene mutation location and the risk of cognitive impairment in Duchenne muscular dystrophy. PLoS One, 5(1), e8803.Google Scholar
Vignos, P. J., Spencer, G. E., & Archibald, K. C. (1963). Management of progressive muscular dystrophy of childhood. Journal of the American Medical Association, 184(2), 89–96.Google Scholar
Wechsler, D. (2004). Wechsler Intelligence Scale for Children-IV(WISC-IV) Manual. San Antonio: The Psychological Corporation: Harcourt Brace and Company.Google Scholar
Weintraub, S., Bauer, P. J., Zelazo, P. D., Wallner-Allen, K., Dikmen, S. S., Heaton, R. K., … Gershon, R. C. (2013). NIH toolbox cognition battery: Introduction and pediatric data. Monographs of the Society for Research in Child Development, 78(4), 1–15.Google Scholar
Wicksell, R. K., Kihlgren, M., Melin, L., & Eeg-Olofsson, O. (2004). Specific cognitive deficits are common in children with Duchenne muscular dystrophy. Developmental Medicine & Child Neurology, 46(3), 154–159.Google Scholar
Wingeier, K., Giger, E., Strozzi, S., Kreis, R., Joncourt, F., Conrad, B., … Steinlin, M. (2011). Neuropsychological impairments and the impact of dystrophin mutations on general cognitive functioning of patients with Duchenne muscular dystrophy. Journal of Clinical Neuroscience, 18(1), 90–95.Google Scholar
Zelazo, P. D., & Bauer, P. J. (Eds.). (2013). National Institutes of Health Toolbox cognition battery (NIH Toolbox CB): Validation for children between 3 and 15 years. Bethesda, MD: Wiley.Google Scholar