{"doi":"10.1111/cge.14697","title":"Novel Phenotypes and Genotype–Phenotype Correlations in a Large Clinical Cohort of Patients With Kleefstra Syndrome","abstract":"Kleefstra syndrome (KLEFS) is a genetic neurodevelopmental disorder caused by haploinsufficiency of EHMT1. The full spectrum of clinical features and genotype-phenotype correlations is currently not fully understood. We performed a retrospective chart review of patients with KLEFS evaluated at the Boston Children's Hospital Kleefstra Clinic. There were 65 individuals (40 females, 25 males, mean age 9.3 years). 17% had large 9q34 deletions (≥ 1 Mb), 29% had small 9q34 deletions (< 1 Mb), and 54% had sequence variants. Global developmental delay (GDD) or intellectual disability (ID) was present in 77%. Behavioral disorders, such as autism spectrum disorder (38%), were common. Epilepsy affected 15%. Systemic health issues included structural cardiac defects (40%), hearing loss (32%), and constipation (31%). Novel features including subgroups with significant motor impairment (24%) and refractory epilepsy (9%), as well as small numbers with opsoclonus-like eye movements (n = 2), thrombocytopenia (n = 2), progressive cerebral atrophy (n = 1), and adrenal carcinoma (n = 1). 9q34 deletion subgroups had higher rates of GDD/ID (p = 0.037), significant motor impairment (p = 0.01), epilepsy (p = 0.004), and cortical visual impairment (p = 0.003) compared to the subgroup with sequence variants. This information may be used to improve clinical care as well as inform research and future therapeutic initiatives.","journal":"Clinical Genetics","year":2025,"id":516290,"datarank":0.38986465225303285,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.04447688830392592,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.04447688830392592,"corpus_percentile":53.291560300146976,"corpus_rank":6039,"citation_count":9,"citer_count":8,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.7237,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1140531,"name":"Seyda Kilic","orcid":"0000-0002-5455-4258","position":1,"is_corresponding":false},{"id":1382113,"name":"Hailey Osika","orcid":null,"position":2,"is_corresponding":false},{"id":879691,"name":"Alisa Mo","orcid":"0000-0002-6435-1227","position":3,"is_corresponding":false},{"id":1382114,"name":"Meg Quinn","orcid":null,"position":4,"is_corresponding":false},{"id":234243,"name":"Sonia Ballal","orcid":null,"position":5,"is_corresponding":false},{"id":1382115,"name":"Tamar Katz","orcid":null,"position":6,"is_corresponding":false},{"id":1156108,"name":"A. Eliot Shearer","orcid":"0000-0002-5324-4805","position":7,"is_corresponding":false},{"id":255919,"name":"Max A. Horlbeck","orcid":"0000-0002-3875-871X","position":8,"is_corresponding":false},{"id":322765,"name":"Lynn Pais","orcid":"0000-0001-9673-4305","position":9,"is_corresponding":false},{"id":397550,"name":"Kira A. Dies","orcid":"0000-0002-0877-8533","position":10,"is_corresponding":false},{"id":995,"name":"Anne H. O’Donnell-Luria","orcid":"0000-0001-6418-9592","position":11,"is_corresponding":false},{"id":502769,"name":"Joe Kossowsky","orcid":"0000-0002-6272-6259","position":12,"is_corresponding":false},{"id":1037274,"name":"Jonathan O. Lipton","orcid":"0000-0002-9648-0541","position":13,"is_corresponding":false},{"id":465614,"name":"Tjitske Kleefstra","orcid":"0000-0002-0956-0237","position":14,"is_corresponding":false},{"id":371860,"name":"Siddharth Srivastava","orcid":"0000-0001-7008-1879","position":15,"is_corresponding":false},{"id":1072318,"name":"Zoë J. Frazier","orcid":null,"position":0,"is_corresponding":true}],"reference_count":28,"raw_metadata":null,"created_at":"2026-07-19T02:48:49.486328Z","pmid":"39746677","pmcid":"PMC12050201","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":[]}