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

ABSTRACT

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.