• Phenotype
• Genetics, Medical
• Genotype

I read with interest the case series and review article ‘Further characterisation of ARX-related disorders in females due to inherited or de novo variants’ by Gras et al1 which summarised the findings of their cohort of 10 new cases and a review of 63 published cases. It is so far the most comprehensive summary of the phenotype of female carriers of the ARX gene mutations, and the authors have confirmed previous findings2 that the clinical spectrum of females carrying ARX variants is very large, from subclinical/asymptomatic to isolated agenesis of the corpus callosum or mild issues such as learning disabilities, autistic features or medication-controlled seizures to severe neurodevelopmental phenotypes, such as intellectual disability and epileptic encephalopathy. The authors reported that severe phenotype was significantly more prevalent in women carrying de novo variants vs in those carrying inherited variants.

Personally, I have two families …