PLXNA1 developmental encephalopathy with syndromic features: A case report and review of the literature

Abstract

Developmental encephalopathies constitute a broad and genetically heterogeneous spectrum of disorders associated with global developmental delay, intellectual disability, frequent epilepsy, and other neurofunctional abnormalities. Here, we report a male presenting with infantile onset epilepsy and syndromic features resembling Dubowitz syndrome identified to have a de novo PLXNA1 variant by whole exome sequencing. This constitutes the second report of PLXNA1 sequence variation associated with early onset epilepsy, and the first to expand on the clinical features of this emerging disorder. This reports suggests that nonsynonymous de novo sequence variations in PLXNA1 are associated with a novel human phenotype characterized by intractable early onset epilepsy, intellectual disability, and syndromic features.

Keywords: PLXNA1; developmental encephalopathy; epilepsy.

FIGURE 1

Clinical photographs and MRI images of PLXNA1 mutation-positive patient. (a) Facial photograph of the patient showing several dysmorphic features including upturned nares, prominent eyebrows and eyelashes, laterally prominent and small ears, low hairline, and angular cheilitis with dermatitis of the philtrum; (b) lateral photograph of the face showing fleshy and laterally prominent earlobes, sparse hair with abnormal hair growth pattern in the temporal areas bilaterally; (c) photograph of the foot showing prominent digit pads on fingers and toes; d–f, T1 weighted sagittal (d), T2-weighted axial (e), and coronal (f) brain MRI images showing moderately dilated third and lateral ventricles, and increased extra-axial spaces predominantly in the frontal region. The cortical gyral pattern is normal [Color figure can be viewed at wileyonlinelibrary.com]