{"doi":"10.1002/ajmg.c.32022","title":"Infantile epileptic spasms syndrome in children with cardiofaciocutanous syndrome: Clinical presentation and associations with genotype","abstract":"Gene variants that dysregulate signaling through the RAS-MAPK pathway cause cardiofaciocutaneous syndrome (CFCS), a rare multi-system disorder. Infantile epileptic spasms syndrome (IESS) and other forms of epilepsy are among the most serious complications. To investigate clinical presentation, treatment outcomes, and genotype-phenotype associations in CFCS patients with IESS, molecular genetics and clinical neurological history were reviewed across two large clinical research cohorts (n = 180). IESS presented in 18/180 (10%) cases, including 16 patients with BRAF variants and 2 with MAP2K1 variants. Among IESS patients with BRAF variants, 16/16 (100%) had sequence changes affecting the protein kinase domain (exons 11-16), although only 57% of total BRAF variants occurred in this domain. Clinical onset of spasms occurred at a median age of 5.4 months (range: 1-24 months). Among 13/18 patients whose IESS resolved with anti-seizure medications, 10 were treated with ACTH and/or vigabatrin. A substantial majority of CFCS patients with IESS subsequently developed other epilepsy types (16/18; 89%). In terms of neurodevelopmental outcomes, gross motor function and verbal communication were more limited in patients with a history of IESS compared to those without IESS. These findings can inform clinical neurological care guidelines for CFCS and development of relevant pre-clinical models for severe epilepsy phenotypes.","journal":"American Journal of Medical Genetics Part C Seminars in Medical Genetics","year":2022,"id":280521,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9645,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":955431,"name":"Dante J. Rogers","orcid":null,"position":1,"is_corresponding":false},{"id":882790,"name":"Samuel J. Kroening","orcid":null,"position":2,"is_corresponding":false},{"id":882788,"name":"Abigail L Zatkalik","orcid":null,"position":3,"is_corresponding":false},{"id":882789,"name":"Ashley E. Whitmarsh","orcid":null,"position":4,"is_corresponding":false},{"id":331071,"name":"Amy E. Roberts","orcid":"0000-0001-5827-8521","position":5,"is_corresponding":false},{"id":281483,"name":"Martin Zenker","orcid":"0000-0003-1618-9269","position":6,"is_corresponding":false},{"id":954982,"name":"Maria Luigia Gambardella","orcid":"0000-0002-4132-6221","position":7,"is_corresponding":false},{"id":954983,"name":"Ilaria Contaldo","orcid":"0000-0002-6795-9641","position":8,"is_corresponding":false},{"id":954984,"name":"Chiara Leoni","orcid":"0000-0002-4089-637X","position":9,"is_corresponding":false},{"id":787109,"name":"Roberta Onesimo","orcid":"0000-0003-3128-6657","position":10,"is_corresponding":false},{"id":286608,"name":"Giuseppe Zampino","orcid":"0000-0002-2661-4831","position":11,"is_corresponding":false},{"id":282715,"name":"Marco Tartaglia","orcid":"0000-0001-7736-9672","position":12,"is_corresponding":false},{"id":954985,"name":"Domenica Battaglia","orcid":"0000-0003-0491-4021","position":13,"is_corresponding":false},{"id":735930,"name":"Elizabeth I. Pierpont","orcid":"0000-0001-7555-8613","position":14,"is_corresponding":false},{"id":735929,"name":"Daniel Kenney‐Jung","orcid":"0000-0002-1541-528X","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":null,"created_at":"2026-07-19T00:29:03.247347Z","pmid":"36448195","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}