biostudies-literatureRodrigues Bento JEuropean Research CouncilMarfan FoundationFonds Wetenschappelijk OnderzoekHartstichtinge1797https://www.ebi.ac.uk/biostudies/studies/S-EPMC8580096biostudies-literatureUnknown9(10)<h4>Background</h4>KCNMA1 mutations have recently been associated with a wide range of dysmorphological, gastro-intestinal, cardiovascular, and neurological manifestations.<h4>Methods</h4>Whole exome sequencing was performed in order to identify the underlying pathogenic mutation in two cases presenting with diverse phenotypical manifestations that did not fit into well-known clinical entities.<h4>Results</h4>In an 8-year-old boy presenting with severe aortic dilatation, facial dysmorphism, and overgrowth at birth a de novo p.Gly375Arg KCNMA1 mutation was identified which has been reported previously in association with gingival hypertrophy, aortic dilatation, and developmental delay. Additionally, in a 30-week-old fetus with severe growth retardation and duodenal atresia a de novo p.Pro805Leu KCNMA1 mutation was identified. The latter has also been reported before in a boy with severe neurological manifestations, including speech delay, developmental delay, and cerebellar dysfunction.<h4>Conclusion</h4>The current report presents the first antenatal presentation of a pathogenic KCNMA1 mutation and confirms the specific association of the p.Gly375Arg variant with early onset aortic root dilatation, gingival hypertrophy, and neonatal overgrowth.Molecular genetics & genomic medicineTwo novel presentations of KCNMA1-related pathology--Expanding the clinical phenotype of a rare channelopathy.PMC8580096G.0447.20Genomia – ERC‐COG‐2017‐771945G.0356.172013T093Woiski MBaldewijns MHendson WVerstraeten AFeben CDe Catte LMeester JLoeys BKempers Mvan Rij MRodrigues Bento JAlaerts MDevriendt KfalseTwo novel presentations of KCNMA1-related pathology--Expanding the clinical phenotype of a rare channelopathy.<h4>Background</h4>KCNMA1 mutations have recently been associated with a wide range of dysmorphological, gastro-intestinal, cardiovascular, and neurological manifestations.<h4>Methods</h4>Whole exome sequencing was performed in order to identify the underlying pathogenic mutation in two cases presenting with diverse phenotypical manifestations that did not fit into well-known clinical entities.<h4>Results</h4>In an 8-year-old boy presenting with severe aortic dilatation, facial dysmorphism, and overgrowth at birth a de novo p.Gly375Arg KCNMA1 mutation was identified which has been reported previously in association with gingival hypertrophy, aortic dilatation, and developmental delay. Additionally, in a 30-week-old fetus with severe growth retardation and duodenal atresia a de novo p.Pro805Leu KCNMA1 mutation was identified. The latter has also been reported before in a boy with severe neurological manifestations, including speech delay, developmental delay, and cerebellar dysfunction.<h4>Conclusion</h4>The current report presents the first antenatal presentation of a pathogenic KCNMA1 mutation and confirms the specific association of the p.Gly375Arg variant with early onset aortic root dilatation, gingival hypertrophy, and neonatal overgrowth.2021-01-01T00:00:00Z2021 Oct2024-10-19T07:16:47.259Z2022-02-11T12:58:56.801ZS-EPMC85800963449941710.1002/mgg3.1797