{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T23:07:47Z","timestamp":1788736067346,"version":"build-2803163510"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Spinal muscular atrophy (SMA) and tuberous sclerosis complex (TSC) are both rare genetic disorders, and their co-occurrence is expected to be exceptionally uncommon. Although risdiplam has demonstrated efficacy in SMA, evidence regarding its use in preterm infants with complex genetic comorbidities remains limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We report preterm monozygotic twins born at 32+5 weeks of gestation with genetically confirmed SMA caused by homozygous deletion of SMN1 exons 7\u20138, with two copies of SMN2. During baseline evaluation prior to presymptomatic treatment, brain magnetic resonance imaging revealed incidental abnormalities, including cortical dysplasia and subependymal nodules, which prompted further genetic testing and led to the diagnosis of TSC with a TSC1 c.1041G&amp;gt;A variant. Presymptomatic risdiplam was initiated at a corrected gestational age of 38+5 weeks. Both twins showed marked improvement in motor function. By 12 months of age, they had achieved independent rolling, unsupported sitting, crawling, and pulling to stand, accompanied by substantial improvements in CHOP INTEND and HINE-2 scores. Risdiplam was well tolerated, and no commonly reported adverse events were observed during follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This report describes the first documented co-occurrence of SMA and TSC in preterm monozygotic twins and suggests that presymptomatic risdiplam may be effective and well tolerated in this complex clinical setting over 1 year of follow-up. These findings also highlight the importance of comprehensive genetic evaluation in infants with SMA who present with atypical neuroimaging or neurological features. Longer-term follow-up is needed to clarify safety, efficacy, and optimal integrated management strategies in patients with complex genetic comorbidities.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1851666","type":"journal-article","created":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T22:10:29Z","timestamp":1788732629000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Presymptomatic risdiplam in preterm monozygotic twins with co-occurring spinal muscular atrophy and tuberous sclerosis complex"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiao-fang","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pediatric Neurology, Chengdu Women\u2019s and Children\u2019s Central Hospital, School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-juan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Chengdu Women\u2019s and Children\u2019s Central Hospital, School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-xiu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Chengdu Women\u2019s and Children\u2019s Central Hospital, School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Chengdu Women\u2019s and Children\u2019s Central Hospital, School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Guang","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Chengdu Women\u2019s and Children\u2019s Central Hospital, School of Medicine, University of Electronic Science and Technology of China","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1056\/NEJMoa2009965","article-title":"Risdiplam in type 1 spinal muscular atrophy","volume":"384","author":"Baranello","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.nmd.2018.01.003","article-title":"Correlation between SMA type and SMN2 copy number revisited: an analysis of 625 unrelated Spanish patients and a compilation of 2834 reported cases","volume":"28","author":"Calucho","year":"2018","journal-title":"Neuromuscul. Disord."},{"key":"B3","doi-asserted-by":"publisher","first-page":"56","DOI":"10.3390\/ijns10030056","article-title":"Systematic review of presymptomatic treatment for spinal muscular atrophy","volume":"10","author":"Cooper","year":"2024","journal-title":"Int. J. Neonatal Screen"},{"key":"B4","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/s13023-018-0870-y","article-title":"Incidence of tuberous sclerosis and age at first diagnosis: new data and emerging trends from a national, prospective surveillance study","volume":"13","author":"Ebrahimi-Fakhari","year":"2018","journal-title":"Orphanet J. Rare Dis."},{"key":"B5","doi-asserted-by":"publisher","first-page":"102436","DOI":"10.1016\/j.rmcr.2026.102436","article-title":"Ten-year follow-up of monozygotic twin sisters with TSC-LAM: a rare case report","volume":"62","author":"Fan","year":"2026","journal-title":"Respir. Med. Case Rep."},{"key":"B6","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1056\/NEJMoa2410120","article-title":"Risdiplam in presymptomatic spinal muscular atrophy","volume":"393","author":"Finkel","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"3699","DOI":"10.1007\/s10072-024-07503-x","article-title":"Exploring variability in cognitive functioning in patients with spinal muscular atrophy: a scoping review","volume":"45","author":"Giannotta","year":"2024","journal-title":"Neurol. Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"20","DOI":"10.3390\/epigenomes9020020","article-title":"Epigenetic Insights into Tuberous Sclerosis Complex, Von Hippel-Lindau Syndrome, and Ataxia-Telangiectasia","volume":"9","author":"Hadjigavriel","year":"2025","journal-title":"Epigenomes"},{"key":"B9","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.nmd.2008.02.001","article-title":"A patient with both Charcot-Marie-Tooth disease (CMT 1A) and mild spinal muscular atrophy (SMA 3)","volume":"18","author":"Jedrzejowska","year":"2008","journal-title":"Neuromuscul. Disord."},{"key":"B10","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1016\/j.ncl.2015.07.004","article-title":"Spinal muscular atrophy","volume":"33","author":"Kolb","year":"2015","journal-title":"Neurol. Clin."},{"key":"B11","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1055\/s-0037-1603349","article-title":"Phenotypic variability and mTOR pathway gene aberrations in familial tuberous sclerosis","volume":"15","author":"Liang","year":"2017","journal-title":"J. Pediatr. Neurol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"6307","DOI":"10.1073\/pnas.96.11.6307","article-title":"A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy","volume":"96","author":"Lorson","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B13","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1186\/s13023-022-02266-0","article-title":"Perfect match: mTOR inhibitors and Tuberous sclerosis complex","volume":"17","author":"Luo","year":"2022","journal-title":"Orphanet J. Rare Dis."},{"key":"B14","doi-asserted-by":"publisher","first-page":"e39076","DOI":"10.1097\/MD.0000000000039076","article-title":"Emphasis on the importance of comprehensive clinical and genetic analysis \u2013 spinal muscular atrophy combined with phenylketonuria: a case report","volume":"103","author":"Ma","year":"2024","journal-title":"Med. Baltim."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.1093\/neuonc\/nov152","article-title":"Differentiating the mTOR inhibitors everolimus and sirolimus in the treatment of Tuberous sclerosis complex","volume":"17","author":"MacKeigan","year":"2015","journal-title":"Neuro Oncol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1110","DOI":"10.1016\/S1474-4422(22)00339-8","article-title":"Safety and efficacy of risdiplam in patients with type 1 spinal muscular atrophy (FIREFISH part 2): secondary analyses from an open-label trial","volume":"21","author":"Masson","year":"2022","journal-title":"Lancet Neurol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1002\/ana.25549","article-title":"Severe brain involvement in 5q spinal muscular atrophy type 0","volume":"86","author":"Mendon\u00e7a","year":"2019","journal-title":"Ann. Neurol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/S1474-4422(21)00367-7","article-title":"Safety and efficacy of once-daily risdiplam in type 2 and non-ambulant type 3 spinal muscular atrophy (SUNFISH part 2): a phase 3, double-blind, randomised, placebo-controlled trial","volume":"21","author":"Mercuri","year":"2022","journal-title":"Lancet Neurol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1093\/hmg\/8.7.1177","article-title":"A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2","volume":"8","author":"Monani","year":"1999","journal-title":"Hum. Mol. Genet."},{"key":"B20","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.pediatrneurol.2013.08.001","article-title":"Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 international Tuberous sclerosis complex consensus conference","volume":"49","author":"Northrup","year":"2013","journal-title":"Pediatr. Neurol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.pediatrneurol.2021.07.011","article-title":"Updated international Tuberous sclerosis complex diagnostic criteria and surveillance and management recommendations","volume":"123","author":"Northrup","year":"2021","journal-title":"Pediatr. Neurol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.ejpn.2010.04.003","article-title":"Central core myopathy with RYR1 mutation masks 5q spinal muscular atrophy","volume":"15","author":"Pandey","year":"2011","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"106884","DOI":"10.1016\/j.phrs.2023.106884","article-title":"Paradigm shift in the treatment of tuberous sclerosis: effectiveness of everolimus","volume":"195","author":"Previtali","year":"2023","journal-title":"Pharmacol. Res."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1307636","DOI":"10.3389\/fncel.2023.1307636","article-title":"Autophagy in spinal muscular atrophy: from pathogenic mechanisms to therapeutic approaches","volume":"17","author":"Rashid","year":"2024","journal-title":"Front. Cell Neurosci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"2083","DOI":"10.1007\/s40120-025-00795-x","article-title":"Safety of risdiplam in Japanese patients with spinal muscular atrophy: a 12-Month interim analysis of a postmarketing surveillance study","volume":"14","author":"Saito","year":"2025","journal-title":"Neurol. Ther."},{"key":"B26","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1186\/s40478-021-01223-5","article-title":"Spinal muscular atrophy autophagy profile is tissue-dependent: differential regulation between muscle and motoneurons","volume":"9","author":"Sansa","year":"2021","journal-title":"Acta Neuropathol. Commun."},{"key":"B27","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1186\/s13023-017-0671-8","article-title":"Prevalence, incidence and carrier frequency of 5q-linked spinal muscular atrophy - a literature review","volume":"12","author":"Verhaart","year":"2017","journal-title":"Orphanet J. Rare Dis."},{"key":"B28","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.ejpn.2006.12.007","article-title":"Coinheritance of mutated SMN1 and MECP2 genes in a child with phenotypic features of spinal muscular atrophy (SMA) type II and Rett syndrome","volume":"11","author":"Voutoufianakis","year":"2007","journal-title":"Eur. J. Paediatr. Neurol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/s12881-018-0611-z","article-title":"A novel TSC2 missense variant associated with a variable phenotype of Tuberous sclerosis complex: case report of a Chinese family","volume":"19","author":"Wang","year":"2018","journal-title":"BMC Med. Genet."},{"key":"B30","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1146\/annurev-genom-102319-103602","article-title":"Twenty-five years of spinal muscular atrophy research: from phenotype to genotype to therapy, and what comes next","volume":"21","author":"Wirth","year":"2020","journal-title":"Annu. Rev. Genomics Hum. Genet."},{"key":"B31","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1016\/j.cell.2006.01.016","article-title":"TOR signaling in growth and metabolism","volume":"124","author":"Wullschleger","year":"2006","journal-title":"Cell"},{"key":"B32","doi-asserted-by":"publisher","first-page":"605611","DOI":"10.3389\/fgene.2021.605611","article-title":"Case report: whole-exome sequencing with MLPA revealed variants in two genes in a patient with combined manifestations of spinal muscular atrophy and Duchenne muscular dystrophy","volume":"12","author":"Xia","year":"2021","journal-title":"Front. Genet."},{"key":"B33","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1097\/FM9.0000000000000109","article-title":"Prenatal phenotypical discrepancy in monozygotic twins with Tuberous sclerosis complex","volume":"4","author":"Xiong","year":"2022","journal-title":"Matern. Fetal Med."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2026.1851666\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T22:10:33Z","timestamp":1788732633000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2026.1851666\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,7]]},"references-count":33,"alternative-id":["10.3389\/fgene.2026.1851666"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2026.1851666","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,7]]},"article-number":"1851666"}}