Understanding Seizures in Malan Syndrome Through Caregiver Reports: A Cross-Sectional Study.

Abstract

Malan syndrome is an ultrarare overgrowth-intellectual disability syndrome caused by NFIX variants, characterized by intellectual disability, postnatal overgrowth, and dysmorphic features. Seizures in Malan syndrome remain poorly understood. We surveyed caregivers of 53 individuals with Malan syndrome. Overall, 55% had seizures or electroencephalographic (EEG) abnormalities. Seizures occurred in 47%, with 28% experiencing drug-resistant epilepsy. The median age of seizure onset was 3 years. Epilepsy classifications included focal (40%) and unknown-onset tonic-clonic seizures (48%). Generalized tonic-clonic (8%), myoclonic (8%), and epileptic spasms (4%) were also reported. Of those with seizures, 44% had status epilepticus. Valproic acid was the most used antiseizure medication, with variable efficacy. This study represents the largest cohort to date, providing detailed descriptions of seizures in Malan syndrome, and lays a foundation for future research phenotyping epilepsy in affected individuals. Clinicians should maintain a high suspicion of seizures and monitor closely for status epilepticus in individuals with Malan syndrome.