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However, the clinical manifestations of this disorder vary widely. <jats:italic>PRRT2<\/jats:italic> encodes a protein expressed in the central nervous system that is mainly localized in the pre-synaptic neurons and is involved in the modulation of synaptic neurotransmitter release. The anomalous function of this gene has been proposed to cause dysregulation of neuronal excitability and cerebral disorders.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Case presentation<\/jats:title>\n<jats:p>We hereby report on a young child followed-up for three years who presents with a spectrum of clinical manifestations such as congenital microcephaly, dysmorphic features, severe intellectual disability, and drug-resistant epileptic encephalopathy in association with a synonymous variant in <jats:italic>PRRT2<\/jats:italic> gene (c.501C\u2009&gt;\u2009T; p.Thr167Ile) of unknown clinical significance variant (VUS) revealed by diagnostic exome sequencing.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Several hypotheses have been advanced on the specific role that <jats:italic>PRRT2<\/jats:italic> gene mutations play to cause the clinical features of affected patients. To our knowledge, the severe phenotype seen in this case has never been reported in association with any clinically actionable variant, as the missense substitution detected in <jats:italic>PRRT2<\/jats:italic> gene. Intriguingly, the same mutation was reported in the healthy father: the action of modifying factors in the affected child may be hypothesized. The report of similar observations could extend the spectrum of clinical manifestations linked to this mutation.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s13052-019-0755-2","type":"journal-article","created":{"date-parts":[[2019,12,4]],"date-time":"2019-12-04T20:03:03Z","timestamp":1575489783000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["PRRT2 gene variant in a child with dysmorphic features, congenital microcephaly, and severe epileptic seizures: genotype-phenotype correlation?"],"prefix":"10.1186","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5600-9560","authenticated-orcid":false,"given":"Piero","family":"Pavone","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni.","family":"Corsello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Yoon","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xena Giada","family":"Pappalardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martino","family":"Ruggieri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona Domenica","family":"Marino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Kyu","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Marino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Falsaperla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,12,4]]},"reference":[{"key":"755_CR1","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/B978-0-444-63326-2.00008-9","volume":"213","author":"C Nobile","year":"2014","unstructured":"Nobile C, Striano P. 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