Novel splice-site and recurrent p.Arg729* CNKSR2 variants in ESES/CSWS: insights into sex-dependent expression.
Adnan Deniz, Eyyüp Üçtepe, Fatma Müjgan Sönmez
✦ AI-curated · Sources linked
Case in brief
This report describes two patients with de novo CNKSR2 variants. A 17-year-old female presented with a novel splice-site variant and a relatively mild phenotype, while an 8-year-old male exhibited a recurrent nonsense variant leading to drug-resistant ESES, autism, and severe language impairment. These cases highlight the variability in clinical presentation associated with CNKSR2 mutations.
What made this case unusual
The female patient exhibited a mild phenotype despite carrying a pathogenic variant, contrasting with the typically severe manifestations seen in hemizygous males.
Diagnostic / clinical pearl
Clinicians should consider CNKSR2 mutations in patients with ESES/CSWS, regardless of sex, due to the potential for variable phenotypic expression.
Why it matters
Understanding the sex-dependent variability in CNKSR2-related disorders can aid in better diagnosis and management of affected individuals, particularly females who may present with milder symptoms.