Two novel presentations of KCNMA1-related pathology--Expanding the clinical phenotype of a rare channelopathy

Abstract

Background: KCNMA1 mutations have recently been associated with a wide range of dysmorphological, gastro-intestinal, cardiovascular, and neurological manifestations.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: KCNMA1 loss-of-function; Liang-Wang syndrome; channelopathy; thoracic aortic aneurysm.

FIGURE 1

Computed tomography scan of chest showing substantial aortic root dilatation (white arrows), (a) pre‐contrast administration; (b) post‐contrast administration

FIGURE 2

Computed tomography scan of brain showing giant circle of Willis

FIGURE 3

Ultrasound image of the duodenal atresia (double bubble) observed in case 2