{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T21:17:49Z","timestamp":1788988669578,"version":"build-2803163510"},"reference-count":14,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,3,11]],"date-time":"2022-03-11T00:00:00Z","timestamp":1646956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Reports"],"abstract":"<jats:p>Diagnosis of pediatric intellectual disability (ID) can be difficult because it is due to a vast number of established and novel causes. Here, we described a full-term female infant affected by Kleefstra syndrome-2 presenting with neurodevelopmental disorder, a history of hypotonia and minor face anomalies. A systematic literature review was also performed. The patient was a 6-year-old Caucasian female. In the family history there was no intellectual disability or genetic conditions. Auxological parameters at birth were adequate for gestational age. Clinical evaluation at 6 months revealed hypotonia and, successively, delay in the acquisition of the stages of psychomotor development. Auditory, visual, somatosensory, and motor-evoked potentials were normal. A brain MRI, performed at 9 months, showed minimal gliotic changes in bilateral occipital periventricular white matter. Neuropsychiatric control, performed at 5 years, established a definitive diagnosis of childhood autism and developmental delay. Molecular analysis of the exome revealed a novel KMT2C missense variant: c.9244C &gt; T (p.Pro3082Ser) at a heterozygous state, giving her a diagnosis of Kleefstra syndrome 2. Parents did not show the variant. Literature review (four retrieved eligible studies, 10 patients) showed that all individuals had mild, moderate, or severe ID; language and motor delay; and autism. Short stature, microcephaly, childhood hypotonia and plagiocephaly were also present. Conclusion. Kleefstra syndrome 2 is a difficult diagnosis of a rare condition with a high clinical phenotypic heterogeneity. This study suggests that it must be taken in account in the work-up of an orphan diagnosis of intellectual disability and\/or autism spectrum disorder.<\/jats:p>","DOI":"10.3390\/pediatric14010019","type":"journal-article","created":{"date-parts":[[2022,3,13]],"date-time":"2022-03-13T21:44:17Z","timestamp":1647207857000},"page":"131-139","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["De Novo Mutation in KMT2C Manifesting as Kleefstra Syndrome 2: Case Report and Literature Review"],"prefix":"10.3390","volume":"14","author":[{"given":"Maria Anna","family":"Siano","sequence":"first","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, Postgraduate School of Pediatrics, University of Salerno, 84084 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilaria","family":"De Maggio","sequence":"additional","affiliation":[{"name":"Medical and Laboratory Genetics Unit, A.O.R.N. \u2018\u2019Antonio Cardarelli\u2019\u2019, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Petillo","sequence":"additional","affiliation":[{"name":"Medical and Laboratory Genetics Unit, A.O.R.N. \u2018\u2019Antonio Cardarelli\u2019\u2019, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Cocciadiferro","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Bambino Ges\u00f9 Children Hospital, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6543-6225","authenticated-orcid":false,"given":"Emanuele","family":"Agolini","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Bambino Ges\u00f9 Children Hospital, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Majolo","sequence":"additional","affiliation":[{"name":"Hospital Directorate, National Hospital A.O.R.N. \u2018\u2019Antonio Cardarelli\u2019\u2019, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9037-4297","authenticated-orcid":false,"given":"Antonio","family":"Novelli","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Bambino Ges\u00f9 Children Hospital, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Della Monica","sequence":"additional","affiliation":[{"name":"Medical and Laboratory Genetics Unit, A.O.R.N. \u2018\u2019Antonio Cardarelli\u2019\u2019, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmelo","family":"Piscopo","sequence":"additional","affiliation":[{"name":"Medical and Laboratory Genetics Unit, A.O.R.N. \u2018\u2019Antonio Cardarelli\u2019\u2019, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1108\/AMHID-10-2015-0050","article-title":"\u201cIntellectual developmental disorders\u201d: Reflections on the international consensus document for redefining \u201cmental retardation-intellectual disability\u201d in ICD-11","volume":"10","author":"Bertelli","year":"2016","journal-title":"Adv. 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