A Unique Case of MBD5 and CCM2 Deletions Leading to a Severe Neurological Phenotype With Prolonged Status Epilepticus

Heterozygous pathogenic variants in MBD5 (MIM*611472) and CCM2 (MIM*607929) cause autosomal dominant intellectual developmental disorder 1 (MIM#156200) and cerebral cavernous malformations-2 (MIM#603284), respectively. Both conditions may present with seizures, epilepsy, and status epilepticus. However, super-refractory status epilepticus, defined as seizures lasting more than 24 h, has not been described in either condition. Herein, we describe the case of a 14-year-old boy with a neurodevelopmental disorder caused by a heterozygous MBD5 deletion as well as multiple cerebral cavernous malformations caused by a CCM2 deletion, who presented with prolonged super-refractory status epilepticus. After 2 months of status epilepticus that was refractory to several anticonvulsants and a ketogenic diet, the patient underwent a surgical corpus callosotomy, which controlled the seizures. Genetic analysis revealed MBD5 and CCM2 deletions. We hypothesize that the co-occurrence of these two deletions in the patient interplayed synergistically, leading to a more severe clinical phenotype than those caused by either of the two independent conditions. We highlight the relevance of corpus callosotomy as a surgical option in severe cases of status epilepticus in which a brain focal resection is not feasible.