Drug-resistant infantile spasms with focal onset in encephalocraniocutaneous lipomatosis harboring a somatic mosaic KRAS mutation: a case report and literature review

Background Encephalocraniocutaneous lipomatosis (ECCL) is a rare neurocutaneous syndrome. The diagnostic detection rate of somatic mosaic KRAS mutations in ECCL has increased with the implementation of high-depth tissue next-generation sequencing (NGS). However, the electroclinical features of seizures and anti-seizure medication (ASM) responses in this subtype remain poorly characterized. Case presentation We report a 10-month-old female infant presenting with the classic ECCL triad: nevus psiloliparus, ocular choristoma, and right cerebral hemispheric dysplasia. She developed frequent epileptic spasms starting at 3 months of age, consistent with a Developmental and Epileptic Encephalopathy (DEE). Video-EEG captured focal-onset spasms with right-hemisphere-predominant electrographic abnormalities. The patient exhibited a suboptimal response to a prolonged trial of first-line hormonal therapy (2-week ACTH followed by a 3-month oral prednisone taper) and subsequent multiple antiseizure medications (ASMs), fulfilling the International League Against Epilepsy (ILAE) criteria for Drug-Resistant Epilepsy (DRE). High-depth whole-exome sequencing (mean depth 150.85×) of the lesional skin tissue confirmed a somatic mosaic KRAS c.35G > A (p.Gly12Asp) mutation (variant allele frequency [VAF] of 19%), while peripheral blood testing was negative. Conclusion This case expands the electroclinical phenotype of KRAS -related ECCL to include focal-onset epileptic spasms within a DEE framework. It highlights a critical diagnostic pitfall: low systemic mosaic burden frequently leads to false-negative peripheral blood genetic tests. Therefore, high-depth sequencing of affected lesional tissue is mandatory for definitive diagnosis when clinical suspicion remains high.