Diana Castro , Thomas Sejersen , Luca Bello , Filippo Buccella , Anita Cairns , Jorge Carranza-del Río , Imelda J.M. de Groot , Lauren Elman , Isabella Inzani , Andrea Klein , Oscar H. Mayer , Hawken Miller , Alessandro Onofri , Alexandra Prufer de Queiroz Campos Araújo , Ulrike Schara-Schmidt , Karsten Vanden Wyngaert , Leanne M. Ward , Jo M. Wilmshurst , Rosaline Quinlivan
{"title":"Transition of patients with Duchenne muscular dystrophy from paediatric to adult care: An international Delphi consensus study","authors":"Diana Castro , Thomas Sejersen , Luca Bello , Filippo Buccella , Anita Cairns , Jorge Carranza-del Río , Imelda J.M. de Groot , Lauren Elman , Isabella Inzani , Andrea Klein , Oscar H. Mayer , Hawken Miller , Alessandro Onofri , Alexandra Prufer de Queiroz Campos Araújo , Ulrike Schara-Schmidt , Karsten Vanden Wyngaert , Leanne M. Ward , Jo M. Wilmshurst , Rosaline Quinlivan","doi":"10.1016/j.ejpn.2025.01.004","DOIUrl":"10.1016/j.ejpn.2025.01.004","url":null,"abstract":"<div><h3>Background</h3><div>Duchenne muscular dystrophy (DMD) is a rare neuromuscular disorder characterized by a progressive decline in muscle function, leading to loss of ambulation, respiratory and cardiac failure, and ultimately death. Improvements in DMD management have increased patient life expectancy; therefore, there is a growing requirement for patients to transfer from paediatric to adult care services. There is also a need for clear recommendations to guide this process.</div></div><div><h3>Aim</h3><div>To establish international consensus guidelines regarding best practices for transitioning patients with DMD from paediatric to adult care and ensuring continuity of treatment.</div></div><div><h3>Methods</h3><div>Consensus statements were developed using the Delphi process and scored using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The initiative was led by a steering committee (one non-voting chair and two voting members) who recruited 15 expert panellists to form the consensus group. Following an initial systematic literature search, the consensus group voted in three voting rounds. Round 1 (free-text responses to questions) and Round 2 (importance ranking of statements) were completed using an online survey. Round 3 (voting on final consensus statements) took place during a virtual consensus meeting.</div></div><div><h3>Consensus statements</h3><div>Consensus was reached on 48 statements covering the topics of transition planning, the transition process, post-transfer management, communicating with young people with DMD and supporting them with the transition to adult life.</div></div><div><h3>Conclusion</h3><div>These consensus statements provide guidelines for improving transition practices for young people with DMD and promoting continued care at a comparable standard in adulthood.</div></div>","PeriodicalId":50481,"journal":{"name":"European Journal of Paediatric Neurology","volume":"54 ","pages":"Pages 130-139"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anthony Mercier , Liam Dorris , Andreas Brunklaus , Joseph D. Symonds , Sameer M. Zuberi , Teresa Finch , Galia Wilson , Claire Eldred
{"title":"Trauma, coping, and adjustment when parenting a child with Dravet syndrome","authors":"Anthony Mercier , Liam Dorris , Andreas Brunklaus , Joseph D. Symonds , Sameer M. Zuberi , Teresa Finch , Galia Wilson , Claire Eldred","doi":"10.1016/j.ejpn.2025.01.002","DOIUrl":"10.1016/j.ejpn.2025.01.002","url":null,"abstract":"<div><h3>Objectives</h3><div>Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy that requires significant caregiver input across the lifespan. This predominantly falls on parents, who are faced with considerable challenges including physical demands, financial burdens, and sustained pressure on mental wellbeing leading to mental health difficulties. We aimed to develop a grounded theory model for the process of coping and adjustment that occurs when caring for a child who has a diagnosis of DS.</div></div><div><h3>Methods</h3><div>Using a Constructivist Grounded Theory methodology, we conducted five focus groups, each with 4–6 participants, and 24 in total. They were recruited via convenience sampling through a national Dravet syndrome patient advocacy group. Focus group dialogue was recorded, transcribed, and coded into themes to generate a theory of coping and adjustment that is grounded in the data.</div></div><div><h3>Results</h3><div>We developed a model of coping and adjustment for parents caring for a child with Dravet syndrome. The model includes contextual factors that impact on parents (loss and insufficient resource). We found a prominent theme of trauma and explored how parents responded to this trauma over time. All parents described a primary coping response reflecting the high levels of stress they had to contend with. Some parents were able to describe a secondary coping style that appeared to support healthier long-term coping and adjustment.</div></div><div><h3>Significance</h3><div>The study provides novel insight into the ways in which parents cope and adjust to caring for a child with DS, with a focus on adapting to trauma. These insights provide the foundation for the creation of targeted therapeutic interventions for parents of children with developmental and epileptic encephalopathies (DEEs), which we outline and discuss.</div></div>","PeriodicalId":50481,"journal":{"name":"European Journal of Paediatric Neurology","volume":"54 ","pages":"Pages 96-106"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Efficacy and safety of Nusinersen among children with spinal muscular atrophy from North India: A prospective cohort study (NICE-SMA study)","authors":"Abhishek Pandey , Renu Suthar , Titiksha Sirari , Manisha Malviya , Somya Saxena , Sandhya Yaddanapudi , Shobit Garg , Arushi G. Saini , Jitendra K. Sahu , Naveen Sankhyan","doi":"10.1016/j.ejpn.2024.12.001","DOIUrl":"10.1016/j.ejpn.2024.12.001","url":null,"abstract":"<div><h3>Background</h3><div>Intra-thecal Nusinersen has been approved for the treatment of Spinal muscular atrophy (SMA). Limited data is available regarding the efficacy and safety of Nusinersen in children with SMA type 2 and 3 from North India.</div></div><div><h3>Objective</h3><div>To study the efficacy and safety of Nusinersen among children with SMA type 2 and 3 from North India compared to standard of care (SOC) over 12 months.</div></div><div><h3>Methods</h3><div>Children with a genetically confirmed diagnosis of SMA and ≥2 copies of the SMN2 gene were screened for enrolment in prospective study design. Revised Hammersmith score (RHS) and revised upper limb module (RULM) were assessed every three months. Compound muscle action potentials (CMAPs) at median and ulnar nerves and quality of life (QOL) were performed at baseline and 12 months. Intra-thecal procedure-related and treatment-emergent side effects in children receiving Nusinersen therapy were recorded. Outcome measures at 6 and 12 months were compared between the Nusinersen and SOC groups.</div></div><div><h3>Results</h3><div>Forty-two children with SMA, mean age of 85 ± 6 months, including 16 in the Nusinersen group and 26 in the SOC group, were enrolled. The mean RHS score in the Nusinersen group increased from the baseline of 35 ± 18 to 38.9 ± 19, and 39.9 ± 17 at 6 and 12 months (p value-0.001), in the SOC group increased from the baseline of 28.8 ± 15, to 29.6 ± 16, and 29.9 ± 17 at 6 and 12 months respectively (p value-0.35). The mean gain in the RHS score over 12 months in the Nusinersen group was significantly higher compared to the SOC group (p-value 0.02). RULM showed significant gain in the Nusinersen group compared to the SOC group over 12 months (p value 0.03). The median and ulnar nerve CMAPs, and QOL were similar in both the groups. A total of 119 intrathecal injections of Nusinersen were given. Most adverse events were mild and related to the intra-thecal procedure.</div></div><div><h3>Conclusion</h3><div>Intra-thecal Nusinersen therapy among children with late-onset SMA from North India over 12-month duration was associated with improvement in motor abilities as measured by RHS compared to SOC. Intra-thecal Nusinersen was safe and tolerated well.</div></div>","PeriodicalId":50481,"journal":{"name":"European Journal of Paediatric Neurology","volume":"54 ","pages":"Pages 42-49"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mari Saarinen , Leena Himanen , Marjaana Raukola-Lindblom , Nina Erkinjuntti , Tero Vahlberg , Anna Rinta-Rahko , Julia Wiklund , Mira Karrasch , Olli Tenovuo , Tuire Lähdesmäki
{"title":"Cognitive performance and perceived injury symptoms in school-aged children and adolescents after mild traumatic brain injury. A long-term follow-up study","authors":"Mari Saarinen , Leena Himanen , Marjaana Raukola-Lindblom , Nina Erkinjuntti , Tero Vahlberg , Anna Rinta-Rahko , Julia Wiklund , Mira Karrasch , Olli Tenovuo , Tuire Lähdesmäki","doi":"10.1016/j.ejpn.2025.02.002","DOIUrl":"10.1016/j.ejpn.2025.02.002","url":null,"abstract":"<div><h3>Background</h3><div>Mild traumatic brain injuries (mTBIs) are common in childhood and adolescence, but their long-term effects remain poorly understood.</div></div><div><h3>Objective</h3><div>Examine cognitive performances and perceived injury symptoms, on average, six years after an mTBI in school-aged children and adolescents, and to evaluate longitudinal changes in performance and symptoms during the follow-up period.</div></div><div><h3>Materials and method</h3><div>Finnish children aged 7–15 years who were cared for mTBI at Turku University Hospital during 2010–2016, with brain imaging and neuropsychological assessment linked to the event available, were identified and targeted for follow-up assessment. We gathered cognitive performance and injury symptom data, as recorded at 1–3 months post-injury, retrospectively from the hospital patient records. Age-appropriate versions of Wechsler Intelligence Scale, Conners Continuous Performance Test II, PedsQL™ Multidimensional Fatigue Scale and semi-structured interview of symptoms were used as outcome measures at follow-up.</div></div><div><h3>Results</h3><div>Age-adjusted verbal performance scores of the participants deteriorated during follow-up, and were predicted by younger age at injury, male sex, and lower verbal performance scores at the original assessment. At follow-up 64.9 % reported one or more injury symptoms, with 48.6 % of those displaying symptoms at the original assessment continuing to report symptoms at follow-up. The most persistent injury symptoms were verbal difficulties, headache and fatigue.</div></div><div><h3>Conclusions</h3><div>The results stress the importance of identifying and monitoring children recovering slowly after a hospital-treated mTBI, as they might be at increased risk for long-lasting problems.</div></div>","PeriodicalId":50481,"journal":{"name":"European Journal of Paediatric Neurology","volume":"54 ","pages":"Pages 159-170"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cannabinoids fail to show efficacy for spasticity in children with cerebral palsy: More research needed","authors":"Sebastian Grunt MD PhD","doi":"10.1016/j.ejpn.2025.02.009","DOIUrl":"10.1016/j.ejpn.2025.02.009","url":null,"abstract":"","PeriodicalId":50481,"journal":{"name":"European Journal of Paediatric Neurology","volume":"54 ","pages":"Page A3"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Beatriz Mansilla Fernández , José Francisco Paz Solís , María del Mar García Romero , Miguel A. Fernandez-Garcia , María Román de Aragón , Fernando Carceller Benito , Samuel Ignacio Pascual Pascual
{"title":"Difficulty of administration of nusinersen in complex-column spinal muscular atrophy: New alternative technique by means of cervical intrathecal access through an Ommaya reservoir","authors":"Beatriz Mansilla Fernández , José Francisco Paz Solís , María del Mar García Romero , Miguel A. Fernandez-Garcia , María Román de Aragón , Fernando Carceller Benito , Samuel Ignacio Pascual Pascual","doi":"10.1016/j.ejpn.2025.01.005","DOIUrl":"10.1016/j.ejpn.2025.01.005","url":null,"abstract":"<div><h3>Background</h3><div>The study aimed to describe a new Ommaya reservoir implantation method in late-onset SMA patients, assessing its safety and effectiveness under standard clinical conditions.</div></div><div><h3>Methods</h3><div>Prospective observational study. Lumbar intrathecal access was unfeasible due to significant scoliosis and prior spinal surgeries with instrumentation. Patients were infused with Nusinersen through the Ommaya reservoir at Hospital Universitario La Paz (Spain) following the standard dosing protocol.</div></div><div><h3>Results</h3><div>The cohort was composed of 6 patients, 5 individuals with type 2 SMA (83.3 %), and 1 patient presenting with type 3 SMA. 4 of the patients were functionally sitters (66.7 %) and 2 had lost this ability prior to initiating treatment (non-sitters). Mean treatment was 34.7 months. Patient discharge was done in all the cases within 48 h post-admission; no significant postoperative complications or during administration of nusinersen were reported. Functional progress was observed in all patients. Hammersmith Functional Motor Scale Expanded (HFMSE) showed a low average increase (1.0), attributed to the severity of baseline functional impairments. Improvements in upper extremity motor function, measured by the Revised Upper Limb Module (RULM), were more pronounced, with an average improvement of 3.3. Disability levels as measured by the Egen Klassifikation 2 (EK2) scale, declined by 4.4.</div></div><div><h3>Conclusion</h3><div>the current study broadens knowledge regarding the efficacy and safety of using an Ommaya reservoir to administer nusinersen in patients with SMA Types 2 and 3. The technique demonstrated rapid, straightforward drug delivery through a subcutaneous needle, maintaining optimal sterility without radiation or the need for a multidisciplinary team.</div></div>","PeriodicalId":50481,"journal":{"name":"European Journal of Paediatric Neurology","volume":"54 ","pages":"Pages 107-112"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nina Barišić , Jakob Nemir , Romana Perković , Manuela Frančić , Raffaela Lombardi
{"title":"Spinal cord stimulation (SCS) induced favorable neuromodulative outcome in the treatment of chronic neuropathic pain syndrome in children","authors":"Nina Barišić , Jakob Nemir , Romana Perković , Manuela Frančić , Raffaela Lombardi","doi":"10.1016/j.ejpn.2025.02.007","DOIUrl":"10.1016/j.ejpn.2025.02.007","url":null,"abstract":"<div><h3>Background</h3><div>Chronic pharmaco-resistant pain syndrome (CPS) requires different therapeutic approaches based on the underlying pathology. Spinal cord stimulation (SCS) in children with chronic neuropathic pain syndrome (CNPS) has been scarcely reported in the literature.</div></div><div><h3>Objectives</h3><div>To present SCS as the rational treatment approach in children with chronic regional and generalized chronic neuropathic pain syndrome, its efficiency, complications and the role in neuromodulation.</div><div>We present two children with chronic pain syndrome treated with SCS. A 14-year-old girl at the age of 8 manifested with signs of chronic regional pain syndrome (CRPS) type 1 in wrist and afterwards in knee, associated with allodynia, signs of local autonomic dysfunction, trophic changes of the skin, and loss of ambulation. Nerve biopsy showed inflammatory infiltrates and loss of small unmyelinated C in skin biopsy.</div><div>A 17-year-old boy manifested at the age of 9 with clinical signs of acute central (CNS) and peripheral nervous system (PNS) involvement associated with headache, photophobia, ataxia, paraparesis, autonomic dysfunction and intensive generalized global neuropathic pain, especially in the lower extremities. Electromyoneurography (EMNG) at the first exam was compatible with Guillain Barre syndrome and subsequently several times during follow up EMNG and nerve biopsy were compatible with chronic inflammatory demyelinating polyneuropathy (CIDP). Treatment was maintained with i.v. immunoglobulins (IVIG) and steroids without functional improvement.</div><div>In both children functional psychosomatic, orthopedic and rheumatologic causes were excluded including painful genetic neuropathies. Seven and eight years after the onset of symptoms and signs of CPS in both children, epidural SCS was implanted, followed by pain relief up to 100 % with complete recovery of motor function, local skin changes and of intraepidermal nerve fiber density in a girl. A boy became ambulant, 50 % up to 75 % pain control was attained, and only partial recovery of sphincter control.</div></div><div><h3>Conclusion</h3><div>SCS as minimally invasive neurosurgical method may be efficient in resolving chronic pain and in restoring functional abilities of affected extremities. SCS should be considered as a treatment approach in children with chronic regional and generalized (pharmacoresistant) neuropathic pain syndrome resistant to all established treatment modalities.</div></div>","PeriodicalId":50481,"journal":{"name":"European Journal of Paediatric Neurology","volume":"54 ","pages":"Pages 186-192"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143438090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K. Martakis , M. Giorgi , M. Spanou , B.A. Neubauer , A. Dinopoulos , A. Hahn
{"title":"N-Acetyl-leucine in progressive CACNA1A ataxia: A case series","authors":"K. Martakis , M. Giorgi , M. Spanou , B.A. Neubauer , A. Dinopoulos , A. Hahn","doi":"10.1016/j.ejpn.2024.12.006","DOIUrl":"10.1016/j.ejpn.2024.12.006","url":null,"abstract":"<div><h3>Background</h3><div>CACNA1A-related disorders are rare and progressive; to date, there is no approved treatment. Trials with N-acetyl-leucine (NAL) demonstrated efficacy in disorders featuring ataxia, cognitive impairment, and epilepsy. Accordingly, we hypothesized that NAL may be effective in CACNA1A-associated disorders.</div></div><div><h3>Cases</h3><div>Four patients (1 boy, age 15 years, 3 girls, age 5, 9, and 14) received NAL as individualized off-label treatment and were assessed using the SARA Score, SCAFI and CGI-I. In all children NAL resulted in rapid improvement of ataxia, (gait, balance, fine motor and speech - mean SARA improvement at first follow-up: 3.25 points). Improvement was sustained up to 3 years (mean long-term SARA improvement: 5.13 points). SCAFI and CGI-I showed similar improvement. NAL was well-tolerated, without adverse reactions.</div></div><div><h3>Conclusions</h3><div>N-acetyl-leucine is a novel potential treatment for a so far untreatable rare disease spectrum of CACNA1A-disorders. The sustained benefit may reflect neuroprotective effects seen in other populations. Clinical trials are needed to control the results.</div></div>","PeriodicalId":50481,"journal":{"name":"European Journal of Paediatric Neurology","volume":"54 ","pages":"Pages 64-67"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143099266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marie Hyland , Laura Gallagher , Ann Connolly , Catherine Comiskey
{"title":"Exploring the psychosocial and educational needs of young people with epilepsy and their parents:A systematic review","authors":"Marie Hyland , Laura Gallagher , Ann Connolly , Catherine Comiskey","doi":"10.1016/j.ejpn.2024.11.009","DOIUrl":"10.1016/j.ejpn.2024.11.009","url":null,"abstract":"","PeriodicalId":50481,"journal":{"name":"European Journal of Paediatric Neurology","volume":"54 ","pages":"Pages 25-31"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Leonela Luce , Chiara Mazzanti , Micaela Carcione , Carmen Llames Massini , Paula Inés Buonfiglio , Viviana Dalamón , Carla Bolaño Díaz , Lilia Mesa , Alberto Dubrovsky , Javier Cotignola , Florencia Giliberto
{"title":"Prognostic significance of ACTN3 genotype in Duchenne muscular dystrophy: Findings from an Argentine patient cohort","authors":"Leonela Luce , Chiara Mazzanti , Micaela Carcione , Carmen Llames Massini , Paula Inés Buonfiglio , Viviana Dalamón , Carla Bolaño Díaz , Lilia Mesa , Alberto Dubrovsky , Javier Cotignola , Florencia Giliberto","doi":"10.1016/j.ejpn.2024.12.003","DOIUrl":"10.1016/j.ejpn.2024.12.003","url":null,"abstract":"<div><div>A wide phenotypic spectrum exists among DMD patients, with genetic modifiers seen as a putative cause of this variability. The main aim was to evaluate the effect of 4 genetic modifiers and the location of <em>DMD</em> variants on disease severity in a DMD Argentine cohort. A secondary objective was to provide a summary of the current state of knowledge and association of the tested loci with DMD's phenotype. Two groups of patients with extreme phenotypes (Severe/Mild) were defined based on the age at loss of ambulation. SNVs in <em>SPP1, LTBP4, CD40</em>, and <em>ACTN3</em> were genotyped, and their distribution was compared between groups using Chi-square or Fisher exact tests. Concurrent effects with glucocorticoids treatment, <em>DMD</em> mutation location (proximal/distal) and the other loci were evaluated by multivariate logistic regression. Additionally, we performed a systematic literature review to summarize and interpret the impact of modifiers on various DMD traits. <em>ACTN3</em>-rs1815739 was the only modifier loci of DMD progression in our cohort. A concurrent damaging effect between <em>DMD</em> mutation and <em>ACTN3</em> was detected, identifying a possible interaction between distal variants and <em>ACTN3</em> TT-genotype that need to be validated in a larger cohort. The systematic review showed agreement in the results when significant differences were reported. The employment of extreme DMD phenotypic groups was an innovative approach for identifying risk loci for disease severity. The interaction between <em>DMD</em> mutation location and <em>ACTN3</em>, if confirmed, could help to avoid confounding elements in assembling study cohorts for clinical trials. Finally, this report's major highlight is being the first study conducted on an Argentine and Latin-American population.</div></div>","PeriodicalId":50481,"journal":{"name":"European Journal of Paediatric Neurology","volume":"54 ","pages":"Pages 32-41"},"PeriodicalIF":2.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}