Gonadal mosaicism and paradoxical phenotype in <i>NEXMIF</i> encephalopathy: a case report of two siblings.

The neurite extension and migration factor (NEXMIF) encephalopathy is an X-linked disorder that is characterized by intellectual disability, behavioural abnormalities and seizures. The majority of pathogenic variants are <i>de novo</i>. Here, we report two siblings with NEXMIF encephalopathy exhibiting variable clinical presentations. The younger female sibling (proband) presented predominantly with refractory myoclonic and atonic epilepsy and milder intellectual disability, and the male sibling exhibited severe intellectual disability, and significant behavioural abnormalities without seizures. Exome sequencing in the proband revealed a novel heterozygous stop gain variant c.3206C>A p.(Ser1069Ter) in the <i>NEXMIF</i> gene, which was validated by Sanger sequencing. Targeted sequencing in the male sibling revealed the hemizygous nature of the variant. The asymptomatic mother was found to carry the wild-type allele, suggesting the possibility of gonadal mosaicism. This report represents the second documented case of <i>NEXMIF</i> encephalopathy associated with gonadal mosaicism.