Advertisement

Dystrophinopathy and the brain: A parent project muscular dystrophy (PPMD) meeting report November 11-12, 2021, New York City, NY

Published:October 20, 2022DOI:https://doi.org/10.1016/j.nmd.2022.10.002

      Highlights

      • Dystrophinopathies entail increased risk of neurodevelopmental and psychiatric conditions.
      • Ongoing research is needed to understand the role of dystrophin in brain development.
      • Clinical care should include screening for developmental delays and neuropsychiatric symptoms.
      • Comprehensive assessment and intervention to support brain and emotional health is critical.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Neuromuscular Disorders
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Doorenweerd N
        • Mahfouz A
        • van Putten M
        • Kaliyaperumal R
        • T'Hoen PAC
        • Hendriksen JGM
        • et al.
        Timing and localization of human dystrophin isoform expression provide insights into the cognitive phenotype of Duchenne muscular dystrophy.
        Sci Rep. 2017; 7: 12575
        • Anderson JL
        • Head SI
        • Rae C
        • Morley JW.
        Brain function in Duchenne muscular dystrophy.
        Brain. 2002; 125 (Pt 1): 4-13
        • Darmahkasih AJ
        • Rybalsky I
        • Tian C
        • Shellenbarger KC
        • Horn PS
        • Lambert JT
        • Wong BL.
        Neurodevelopmental, behavioral, and emotional symptoms common in Duchenne muscular dystrophy.
        Muscle Nerve. 2020; 61: 466-474
        • Hendriksen JGM
        • Thangarajh M
        • Kan HE
        • Muntoni F
        ENMC 249th workshop study group. 249th ENMC international workshop: the role of brain dystrophin in muscular dystrophy: implications for clinical care and translational research, Hoofddorp, The Netherlands, November 29th-December 1st 2019.
        Neuromuscul Disord. 2020; 30: 782-794
        • Doorenweerd N.
        Combining genetics, neuropsychology and neuroimaging to improve understanding of brain involvement in Duchenne muscular dystrophy - a narrative review.
        Neuromuscul Disord. 2020; 30: 437-442
        • Preethish-Kumar V
        • Shah A
        • Kumar M
        • Ingalhalikar M
        • Polavarapu K
        • Afsar M
        • et al.
        In vivo evaluation of white matter abnormalities in children with duchenne muscular dystrophy using DTI.
        Am J Neuroradiol. 2020; 41: 1271-1278
        • Lambert JT
        • Darmahkasih AJ
        • Horn PS
        • Rybalsky I
        • Shellenarger KC
        • Tian C
        • Wong BL.
        Neurodevelopmental, behavioral, and emotional symptoms in Becker muscular dystrophy.
        Muscle Nerve. 2020; 61: 156-162
        • Ricotti V
        • Mandy WP
        • Scoto M
        • Pane M
        • Deconinck N
        • Messina S
        • et al.
        Neurodevelopmental, emotional, and behavioural problems in Duchenne muscular dystrophy in relation to underlying dystrophin gene mutations.
        Dev Med Child Neurol. 2016; 58: 77-84
        • Saoudi A
        • Zarrouki F
        • Sebrié C
        • Izabelle C
        • Goyenvalle A
        • Vaillend C.
        Emotional behavior and brain anatomy of the mdx52 mouse model of Duchenne muscular dystrophy.
        Dis Model Mech. 2021; 14dmm049028
        • Hashimoto Y
        • Kuniishi H
        • Sakai K
        • Fukushima Y
        • Du X
        • Yamashiro K
        • et al.
        Brain Dp140 alters glutamatergic transmission and social behaviour in the mdx52 mouse model of Duchenne muscular dystrophy.
        Prog Neurobiol. 2022; 216102288
        • Lidov HG.
        Dystrophin in the nervous system.
        Brain Pathol. 1996; 6: 63-77
        • Górecki DC
        • Monaco AP
        • Derry JM
        • Walker AP
        • Barnard EA
        • Barnard PJ.
        Expression of four alternative dystrophin transcripts in brain regions regulated by different promoters.
        Hum Mol Genet. 1992; 1: 505-510
        • Bladen CL
        • Salgado D
        • Monges S
        • Foncuberta ME
        • Kekou K
        • Kosma K
        • et al.
        The TREAT-NMD DMD Global Database: analysis of more than 7000 Duchenne muscular dystrophy mutations.
        Hum Mutat. 2015; 36: 395-402
        • Lee JS
        • Pfund Z
        • Juhasz C
        • Behen ME
        • Muzik O
        • Chugani DC
        • et al.
        Altered regional brain glucose metabolism in Duchenne muscular dystrophy: a PET study.
        Muscle Nerve. 2002; 26: 506-512
        • Mori-Yoshimura M
        • Aizawa K
        • Shigemoto Y
        • Ishihara N
        • Minami N
        • Nishino I
        • et al.
        Frontal lobe dominant cerebral blood flow reduction and atrophy can be progressive in Duchenne muscular dystrophy.
        Neuromuscul Disord. 2022; 32: 477-485
        • al-Qudah AA
        • Kobayashi J
        • Chuang S
        • Dennis M
        • Ray P.
        Etiology of intellectual impairment in Duchenne muscular dystrophy.
        Pediatr Neurol. 1990; 6: 57-59
        • Doorenweerd N
        • Straathof CS
        • Dumas EM
        • Spitali P
        • Ginjaar IB
        • Wokke BH
        • et al.
        Reduced cerebral gray matter and altered white matter in boys with Duchenne muscular dystrophy.
        Ann Neurol. 2014; 76: 403-411
        • Doorenweerd N
        • Dumas EM
        • Ghariq E
        • Schmid S
        • Straathof CS
        • Roest AA
        • et al.
        Decreased cerebral perfusion in Duchenne muscular dystrophy patients.
        Neuromuscul Disord. 2017; 27: 29-37
        • Doorenweerd N
        • de Rover M
        • Marini-Bettolo C
        • Hollingsworth KG
        • Niks EH
        • Hendriksen JGM
        • et al.
        Resting-state functional MRI shows altered default-mode network functional connectivity in Duchenne muscular dystrophy patients.
        Brain Imaging Behav. 2021; 15: 2297-2307
        • Hinton VJ
        • Nereo NE
        • Fee RJ
        • Cyrulnik SE.
        Social behavior problems in boys with Duchenne muscular dystrophy.
        J Dev Behav Pediatr. 2006; 27: 470-476
        • Cyrulnik SE
        • Fee RJ
        • De Vivo DC
        • Goldstein E
        • Hinton VJ.
        Delayed developmental language milestones in children with Duchenne's muscular dystrophy.
        J Pediatr. 2007; 150: 474-478
        • Hinton VJ
        • Fee RJ
        • De Vivo DC
        • Goldstein E.
        Poor facial affect recognition among boys with Duchenne muscular dystrophy.
        J Autism Dev Disord. 2007; 37: 1925-1933
        • Hinton VJ
        • Fee RJ
        • Goldstein EM
        • De Vivo DC.
        Verbal and memory skills in males with Duchenne muscular dystrophy.
        Dev Med Child Neurol. 2007; 49: 123-128
        • Thangarajh M
        • Spurney CF
        • Gordish-Dressman H
        • Clemens PR
        • Hoffman EP
        • McDonald CM
        • et al.
        Neurodevelopmental needs in young boys with duchenne muscular dystrophy (DMD): observations from the cooperative international neuromuscular research group (CINRG) DMD natural history study (DNHS).
        PLoS Curr. 2018; 10 (ecurrents.md.4cdeb6970e54034db2bc3dfa54b4d987)
        • Wu JY
        • Kuban KC
        • Allred E
        • Shapiro F
        • Darras BT.
        Association of Duchenne muscular dystrophy with autism spectrum disorder.
        J Child Neurol. 2005; 20: 790-795
        • Hendriksen JG
        • Vles JS.
        Neuropsychiatric disorders in males with duchenne muscular dystrophy: frequency rate of attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder, and obsessive-compulsive disorder.
        J Child Neurol. 2008; 23: 477-481
        • Sekiguchi M
        • Zushida K
        • Yoshida M
        • Maekawa M
        • Kamichi S
        • Yoshida M
        • et al.
        A deficit of brain dystrophin impairs specific amygdala GABAergic transmission and enhances defensive behaviour in mice.
        Brain. 2009; 132 (Pt 1): 124-135
        • Vaillend C
        • Billard JM
        • Claudepierre T
        • Rendon A
        • Dutar P
        • Ungerer A.
        Spatial discrimination learning and CA1 hippocampal synaptic plasticity in mdx and mdx3cv mice lacking dystrophin gene products.
        Neuroscience. 1998; 86: 53-66
        • Vaillend C
        • Billard JM
        • Laroche S.
        Impaired long-term spatial and recognition memory and enhanced CA1 hippocampal LTP in the dystrophin-deficient Dmd(mdx) mouse.
        Neurobiol Dis. 2004; 17: 10-20
        • Vaillend C
        • Rendon A
        • Misslin R
        • Ungerer A
        Influence of dystrophin-gene mutation on mdx mouse behavior. I. Retention deficits at long delays in spontaneous alternation and bar-pressing tasks.
        Behav Genet. 1995; 25: 569-579
        • Di Angelantonio S
        • De Stefano ME
        • Piccioni A
        • Lombardi L
        • Gotti C
        • Paggi P.
        Lack of dystrophin functionally affects α3β2/β4-nicotinic acethylcholine receptors in sympathetic neurons of dystrophic mdx mice.
        Neurobiol Dis. 2011; 41: 528-537
        • Yang TT
        • Simmons AN
        • Matthews SC
        • Tapert SF
        • Bischoff-Grethe A
        • Frank GK
        • et al.
        Increased amygdala activation is related to heart rate during emotion processing in adolescent subjects.
        Neurosci Lett. 2007; 428: 109-114
        • Hessl D
        • Rivera S
        • Koldewyn K
        • Cordeiro L
        • Adams J
        • Tassone F
        • et al.
        Amygdala dysfunction in men with the fragile X premutation.
        Brain. 2007; 130 (Pt): 404-416
        • Kim SY
        • Burris J
        • Bassal F
        • Koldewyn K
        • Chattarji S
        • Tassone F
        • et al.
        Fear-specific amygdala function in children and adolescents on the fragile x spectrum: a dosage response of the FMR1 gene.
        Cereb Cortex. 2014; 24: 600-613
        • Hinton VJ
        • De Vivo DC
        • Nereo NE
        • Goldstein E
        • Stern Y.
        Selective deficits in verbal working memory associated with a known genetic etiology: the neuropsychological profile of duchenne muscular dystrophy.
        J Int Neuropsychol Soc. 2001; 7: 45-54
        • Donders J
        • Taneja C.
        Neurobehavioral characteristics of children with Duchenne muscular dystrophy.
        Child Neuropsychol. 2009; 15: 295-304
        • Leaffer EB
        • Fee RJ
        • Hinton VJ.
        Digit span performance in children with dystrophinopathy: a verbal span or working memory contribution?.
        J Int Neuropsychol Soc. 2016; 22: 777-784
        • Fee RJ
        • Hinton VJ.
        Resilience in children diagnosed with a chronic neuromuscular disorder.
        J Dev Behav Pediatr. 2011; 32: 644-650
        • Gocheva V
        • Schmidt S
        • Orsini AL
        • Hafner P
        • Schaedelin S
        • Weber P
        • Fischer D.
        Psychosocial adjustment and parental stress in Duchenne Muscular Dystrophy.
        Eur J Paediatr Neurol. 2019; 23: 832-841
        • Connolly AM
        • Florence JM
        • Cradock MM
        • Malkus EC
        • Schierbecker JR
        • Siener CA
        • et al.
        Motor and cognitive assessment of infants and young boys with duchenne muscular dystrophy: results from the muscular dystrophy association DMD clinical research network.
        Neuromuscul Disord. 2013; 23: 529-539
        • Connolly AM
        • Florence JM
        • Cradock MM
        • Eagle M
        • Flanigan KM
        • McDonald CM
        • et al.
        One year outcome of boys with Duchenne muscular dystrophy using the Bayley-III scales of infant and toddler development.
        Pediatr Neurol. 2014; 50: 557-563
        • Connolly AM
        • Zaidman CM
        • Golumbek PT
        • Cradock MM
        • Flanigan KM
        • Kuntz NL
        • et al.
        Twice-weekly glucocorticosteroids in infants and young boys with Duchenne muscular dystrophy.
        Muscle Nerve. 2019; 59: 650-657
        • Hendriksen JG
        • Poysky JT
        • Schrans DG
        • Schouten EG
        • Aldenkamp AP
        • Vles JS.
        Psychosocial adjustment in males with Duchenne muscular dystrophy: psychometric properties and clinical utility of a parent-report questionnaire.
        J Pediatr Psychol. 2009; 34 (Jan-Feb): 69-78
        • American Psychiatric Association
        Neurodevelopmental disorders.
        Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 5th ed. American Psychiatric Publishing, 2013
        • Olfson M
        • He JP
        • Merikangas KR.
        Psychotropic medication treatment of adolescents: results from the national comorbidity survey-adolescent supplement.
        J Am Acad Child Adolesc Psychiatry. 2013; 52: 378-388
        • Araz Altay M
        • Bozatlı L
        • Demirci Şipka B
        • Görker I
        Current pattern of psychiatric comorbidity and psychotropic drug prescription in child and adolescent patients.
        Medicina (Kaunas). 2019; 55: 159
        • Zuckerbrot RA
        • Cheung AH
        • Jensen PS
        • Stein RE
        • Laraque D.
        Guidelines for adolescent depression in primary care (GLAD-PC): I. Identification, assessment, and initial management.
        Pediatrics. 2007; 120 (–e1312): e1299
        • Oliva V
        • Lippi M
        • Paci R
        • Del Fabro L
        • Delvecchio G
        • Brambilla P
        • et al.
        Gastrointestinal side effects associated with antidepressant treatments in patients with major depressive disorder: A systematic review and meta-analysis.
        Prog Neuropsychopharmacol Biol Psychiatry. 2021; 109110266
        • Colvin MK
        • Poysky J
        • Kinnett K
        • Damiani M
        • Gibbons M
        • Hoskin J
        • et al.
        Psychosocial management of the patient with duchenne muscular dystrophy.
        Pediatrics. 2018; 142 (Suppl): S99-S109
        • Walkup J
        • Work Group on Quality Issues
        Practice parameter on the use of psychotropic medication in children and adolescents.
        J Am Acad Child Adolesc Psychiatry. 2009; 48: 961-973
        • Pliszka SR
        • Crismon ML
        • Hughes CW
        • Corners CK
        • Emslie GJ
        • Jensen PS
        • et al.
        The Texas children's medication algorithm project: revision of the algorithm for pharmacotherapy of attention-deficit/hyperactivity disorder.
        J Am Acad Child Adolesc Psychiatry. 2006; 45: 642-657
        • Steiner H
        • Remsing L
        Work Group on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with oppositional defiant disorder.
        J Am Acad Child Adolesc Psychiatry. 2007; 46: 126-141
        • Pappadopulos E
        • Rosato NS
        • Correll CU
        • Findling RL
        • Lucas J
        • Crystal S
        • et al.
        Experts' recommendations for treating maladaptive aggression in youth.
        J Child Adolesc Psychopharmacol. 2011; 21: 505-515
        • Doyle CA
        • McDougle CJ.
        Pharmacologic treatments for the behavioral symptoms associated with autism spectrum disorders across the lifespan.
        Dialogues Clin Neurosci. 2012; 14: 263-279
        • Schreibman L
        • Dawson G
        • Stahmer AC
        • Landa R
        • Rogers SJ
        • McGee GG
        • et al.
        Naturalistic developmental behavioral interventions: empirically validated treatments for autism spectrum disorder.
        J Autism Dev Disord. 2015; 45: 2411-2428
        • Wong C
        • Odom SL
        • Hume KA
        • Cox AW
        • Fettig A
        • Kucharczyk S
        • et al.
        Evidence-based practices for children, youth, and young adults with autism spectrum disorder: a comprehensive review.
        J Autism Dev Disord. 2015; 45: 1951-1966
        • Greene RW
        • Ablon JS.
        Treating Explosive Kids: The Collaborative Problem-Solving Approach.
        Guilford Press, New York, NY2006
        • Pollastri AR
        • Epstein LD
        • Heath GH
        • Ablon JS.
        The collaborative problem solving approach: outcomes across settings.
        Harv Rev Psychiatry. 2013; 21: 188-199
        • Mah JK
        • Thannhauser JE
        • Kolski H
        • Dewey D.
        Parental stress and quality of life in children with neuromuscular disease.
        Pediatr Neurol. 2008; 39: 102-107
        • Boyer F
        • Drame M
        • Morrone I
        • Novella JL.
        Factors relating to carer burden for families of persons with muscular dystrophy.
        J Rehabil Med. 2006; 38: 309-315
        • Reid DT
        • Renwick RM.
        Relating familial stress to the psychosocial adjustment of adolescents with Duchenne muscular dystrophy.
        Int J Rehabil Res. 2001; 24: 83-93
        • Landfeldt E
        • Lindgren P
        • Bell CF
        • Guglieri M
        • Straub V
        • Lochmuller H
        • Bushby K.
        Health-related quality of life in patients with Duchenne muscular dystrophy: a multinational, cross-sectional study.
        Dev Med Child Neurol. 2016; 58: 508-515
        • Tesei A
        • Nobile M
        • Colombo P
        • Civati F
        • Gandossini S
        • Mani E
        • et al.
        Mental health and coping strategies in families of children and young adults with muscular dystrophies.
        J Neurol. 2020; 267: 2054-2069
        • Pangalila RF
        • van den Bos GA
        • Stam HJ
        • van Exel NJ
        • Brouwer WB
        • Roebroeck ME.
        Subjective caregiver burden of parents of adults with Duchenne muscular dystrophy.
        Disabil Rehabil. 2012; 34: 988-996
        • Peay HL
        • Meiser B
        • Kinnett K
        • Tibben A.
        Psychosocial needs and facilitators of mothers caring for children with duchenne/becker muscular dystrophy.
        J Genet Couns. 2018; 27: 197-203
        • Pascoe JE
        • Sawnani H
        • Hater B
        • Sketch M
        • Modi AC.
        Understanding adherence to noninvasive ventilation in youth with Duchenne muscular dystrophy.
        Pediatr Pulmonol. 2019; 54: 2035-2043
        • Nereo NE
        • Fee RJ
        • Hinton VJ.
        Parental stress in mothers of boys with Duchenne muscular dystrophy.
        J Pediatr Psychol. 2003; 28: 473-484
        • Magliano L
        • D'Angelo MG
        • Vita G
        • Pane M
        • D'Amico A
        • Balottin U
        • et al.
        Psychological and practical difficulties among parents and healthy siblings of children with Duchenne vs. Becker muscular dystrophy: an Italian comparative study.
        Acta Myol. 2014; 33: 136-143
        • Read J
        • Kinali M
        • Muntoni F
        • Garralda ME.
        Psychosocial adjustment in siblings of young people with Duchenne muscular dystrophy.
        Eur J Paediatr Neurol. 2010; 14: 340-348
        • Read J
        • Kinali M
        • Muntoni F
        • Weaver T
        • Garralda ME.
        Siblings of young people with Duchenne muscular dystrophy–a qualitative study of impact and coping.
        Eur J Paediatr Neurol. 2011; 15: 21-28
        • Samson A
        • Tomiak E
        • Dimillo J
        • Lavigne R
        • Miles S
        • Choquette M
        • et al.
        The lived experience of hope among parents of a child with Duchenne muscular dystrophy: perceiving the human being beyond the illness.
        Chronic Illn. 2009; 5: 103-114
        • Bell M
        • Biesecker BB
        • Bodurtha J
        • Peay HL.
        Uncertainty, hope, and coping efficacy among mothers of children with Duchenne/Becker muscular dystrophy.
        Clin Genet. 2019; 95: 677-683