{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T18:42:59Z","timestamp":1789152179367,"version":"build-2803163510"},"reference-count":23,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017581","name":"University of Rwanda","doi-asserted-by":"crossref","award":["RWA210001-10016"],"award-info":[{"award-number":["RWA210001-10016"]}],"id":[{"id":"10.13039\/100017581","id-type":"DOI","asserted-by":"crossref"}]},{"award":["RWA210001-10016"],"award-info":[{"award-number":["RWA210001-10016"]}],"id":[{"id":"https:\/\/ror.org\/00286hs46","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011858","name":"African Academy of Sciences","doi-asserted-by":"crossref","award":["DCI-PAN AF\/2020\/420-028"],"award-info":[{"award-number":["DCI-PAN AF\/2020\/420-028"]}],"id":[{"id":"10.13039\/501100011858","id-type":"DOI","asserted-by":"crossref"}]},{"award":["DCI-PAN AF\/2020\/420-028"],"award-info":[{"award-number":["DCI-PAN AF\/2020\/420-028"]}],"id":[{"id":"https:\/\/ror.org\/05px9k635","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Kleefstra syndrome (KS) is a rare neurodevelopmental disorder caused by haploinsufficiency of EHMT1; it is characterized by global developmental delay, intellectual disability, hypotonia, distinctive facial features, and variable congenital anomalies. Autistic features, behavioral abnormalities and severe speech impairment are frequently reported. However, molecularly confirmed cases of KS from Africa remain extremely limited, largely due to restricted access to genomic diagnostic infrastructures. Methods: We describe a 15-month-old patient from Rwanda presenting with neonatal hypotonia, global developmental delay, short stature, and characteristic dysmorphic facial features. Comprehensive clinical evaluation was performed, followed by trio-based exome sequencing to identify the underlying genetic cause of this neurodevelopmental disorder. Results: Exome sequencing identified a de novo heterozygous frameshift variant in EHMT1 (NM_024757.5: c.2871dup; p. Phe958Leufs*219), confirming the diagnosis of KS. Conclusions: This report presents the first molecularly confirmed case of KS in Rwanda. It highlights additional clinical features like bilateral 5th toe clinodactyly, short stature and absence of obesity in KS. There is a need to further delineate the study of EHMT1 and investigate the natural history of KS across different populations for optimal patient management and to reduce diagnostic odyssey. The diagnostic utility of exome sequencing for neurodevelopmental disorders needs to be strengthened, with strong emphasis on expanding genomic medicine to help diagnose rare diseases in resource-limited settings.<\/jats:p>","DOI":"10.3390\/genes17040429","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T09:40:31Z","timestamp":1775554831000},"page":"429","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The First Case of Kleefstra Syndrome in a Rwandan Patient with Global Developmental Delay"],"prefix":"10.3390","volume":"17","author":[{"given":"Norbert","family":"Dukuze","sequence":"first","affiliation":[{"name":"Center for Human Genetics, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, KG 11 Ave Gasabo, Kigali P.O. Box 3286, Rwanda"},{"name":"Department of Biochemistry, Molecular Biology and Genetics, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Kigali P.O. Box 4285, Rwanda"},{"name":"Center for Human Genetics, Centre Hospitalier Universitaire Sart-Tilman, University of Liege, Sart Tilman, 4000 Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5197-4559","authenticated-orcid":false,"given":"Janvier","family":"Hitayezu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Teaching Hospital of Kigali (CHUK), Kigali P.O. Box 655, Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1442-4616","authenticated-orcid":false,"given":"Jeanne Primitive","family":"Uyisenga","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science and Technology, University of Rwanda, Kigali P.O. Box 3900, Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2046-9495","authenticated-orcid":false,"given":"Esther","family":"Uwibambe","sequence":"additional","affiliation":[{"name":"Center for Human Genetics, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, KG 11 Ave Gasabo, Kigali P.O. Box 3286, Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Hubert","family":"Caberg","sequence":"additional","affiliation":[{"name":"Center for Human Genetics, Centre Hospitalier Universitaire Sart-Tilman, University of Liege, Sart Tilman, 4000 Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinciane","family":"Dideberg","sequence":"additional","affiliation":[{"name":"Center for Human Genetics, Centre Hospitalier Universitaire Sart-Tilman, University of Liege, Sart Tilman, 4000 Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Bours","sequence":"additional","affiliation":[{"name":"Center for Human Genetics, Centre Hospitalier Universitaire Sart-Tilman, University of Liege, Sart Tilman, 4000 Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5462-9950","authenticated-orcid":false,"given":"Abdullateef Isiaka","family":"Alagbonsi","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Kigali P.O. Box 3286, Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon","family":"Mutesa","sequence":"additional","affiliation":[{"name":"Center for Human Genetics, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, KG 11 Ave Gasabo, Kigali P.O. Box 3286, Rwanda"},{"name":"Department of Biochemistry, Molecular Biology and Genetics, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Kigali P.O. Box 4285, Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1749-0395","authenticated-orcid":false,"given":"Annette","family":"Uwineza","sequence":"additional","affiliation":[{"name":"Center for Human Genetics, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, KG 11 Ave Gasabo, Kigali P.O. Box 3286, Rwanda"},{"name":"Department of Biochemistry, Molecular Biology and Genetics, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Kigali P.O. Box 4285, Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1136\/jmg.2004.028464","article-title":"Disruption of the gene Euchromatin Histone Methyl Transferase1 (Eu-HMTase1) is associated with the 9q34 subtelomeric deletion syndrome","volume":"42","author":"Kleefstra","year":"2005","journal-title":"J. Med. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Koemans, T.S., Kleefstra, T., Chubak, M.C., Stone, M.H., Reijnders, M.R.F., de Munnik, S., Willemsen, M.H., Fenckova, M., Stumpel, C.T.R.M., and Bok, L.A. (2017). 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