{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:54:59Z","timestamp":1790952899378,"version":"4.1.0"},"reference-count":79,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T00:00:00Z","timestamp":1709078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Juvenile Amyotrophic Lateral Sclerosis is a genetically heterogeneous neurodegenerative disorder, which is frequently misdiagnosed due to low clinical suspicion and little knowledge about disease characteristics. More than 20 different genetic loci have been associated with both sporadic and familial juvenile Amyotrophic Lateral Sclerosis. Currently, almost 40% of cases have an identifiable monogenic basis; type 6, associated with FUS gene variants, is the most prevalent globally. Despite several upper motor neuron-dominant forms being generally associated with long-standing motor symptoms and slowly progressive course, certain subtypes with lower motor neuron-dominant features and early bulbar compromise lead to rapidly progressive motor handicap. For some monogenic forms, there is a well-established genotypic-phenotypic correlation. There are no specific biochemical and neuroimaging biomarkers for the diagnosis of juvenile Amyotrophic Lateral Sclerosis. There are several inherited neurodegenerative and neurometabolic disorders which can lead to the signs of motor neuron impairment. This review emphasizes the importance of high clinical suspicion, assessment, and proper diagnostic work-up for juvenile Amyotrophic Lateral Sclerosis.<\/jats:p>","DOI":"10.3390\/genes15030311","type":"journal-article","created":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T03:37:57Z","timestamp":1709091477000},"page":"311","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Clinical and Genetic Aspects of Juvenile Amyotrophic Lateral Sclerosis: A Promising Era Emerges"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7416-7108","authenticated-orcid":false,"given":"Paulo Victor Sgobbi de","family":"Souza","sequence":"first","affiliation":[{"name":"Motor Neuron Disease Unit, Division of Neuromuscular Diseases, Federal University of Sao Paulo (UNIFESP), Sao Paulo 04039-060, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo de Lima","family":"Serrano","sequence":"additional","affiliation":[{"name":"Motor Neuron Disease Unit, Division of Neuromuscular Diseases, Federal University of Sao Paulo (UNIFESP), Sao Paulo 04039-060, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor Braga","family":"Farias","sequence":"additional","affiliation":[{"name":"Motor Neuron Disease Unit, Division of Neuromuscular Diseases, Federal University of Sao Paulo (UNIFESP), Sao Paulo 04039-060, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta Ismael Lacerda","family":"Machado","sequence":"additional","affiliation":[{"name":"Motor Neuron Disease Unit, Division of Neuromuscular Diseases, Federal University of Sao Paulo (UNIFESP), Sao Paulo 04039-060, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno de Mattos Lombardi","family":"Badia","sequence":"additional","affiliation":[{"name":"Motor Neuron Disease Unit, Division of Neuromuscular Diseases, Federal University of Sao Paulo (UNIFESP), Sao Paulo 04039-060, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9lvia Bertoldo de","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Motor Neuron Disease Unit, Division of Neuromuscular Diseases, Federal University of Sao Paulo (UNIFESP), Sao Paulo 04039-060, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alana Strucker","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Motor Neuron Disease Unit, Division of Neuromuscular Diseases, Federal University of Sao Paulo (UNIFESP), Sao Paulo 04039-060, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila Alves","family":"Pereira","sequence":"additional","affiliation":[{"name":"Motor Neuron Disease Unit, Division of Neuromuscular Diseases, Federal University of Sao Paulo (UNIFESP), Sao Paulo 04039-060, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa de Freitas","family":"Moreira","sequence":"additional","affiliation":[{"name":"Motor Neuron Disease Unit, Division of Neuromuscular Diseases, Federal University of Sao Paulo (UNIFESP), Sao Paulo 04039-060, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco Ant\u00f4nio Troccoli","family":"Chieia","sequence":"additional","affiliation":[{"name":"Motor Neuron Disease Unit, Division of Neuromuscular Diseases, Federal University of Sao Paulo (UNIFESP), Sao Paulo 04039-060, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4778-0636","authenticated-orcid":false,"given":"Adriel R\u00eago","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Motor Neuron Disease Unit, Division of Neuromuscular Diseases, Federal University of Sao Paulo (UNIFESP), Sao Paulo 04039-060, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6736-2928","authenticated-orcid":false,"given":"Vin\u00edcius Lopes","family":"Braga","sequence":"additional","affiliation":[{"name":"Motor Neuron Disease Unit, Division of Neuromuscular Diseases, Federal University of Sao Paulo (UNIFESP), Sao Paulo 04039-060, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0150-525X","authenticated-orcid":false,"given":"Wladimir Bocca Vieira de Rezende","family":"Pinto","sequence":"additional","affiliation":[{"name":"Motor Neuron Disease Unit, Division of Neuromuscular Diseases, Federal University of Sao Paulo (UNIFESP), Sao Paulo 04039-060, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6986-4937","authenticated-orcid":false,"given":"Acary Souza Bulle","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Motor Neuron Disease 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