Cardiac Investigations in Sudden Unexpected Death in DEPDC5‐Related Epilepsy

• DOI: 10.1002/ana.26256
• Publication Date: 2021-10-25T06:11:27Z
• Authors: Alexandre Bacq; Delphine Roussel; Thomas Bonduelle; Sara Zagaglia; Marina Maletic; Théo Ribierre; Homa Adle‐Biassette; Cécile Marchal; Mélanie Jennesson; Isabelle An; ; Fabienne Picard; Vincent Navarro; Sanjay M. Sisodiya; Stéphanie Baulac
• Keywords: Adult; Male; Adolescent; [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology; Electrocardiography; Mice; Young Adult; 03 medical and health sciences; 0302 clinical medicine; Animals; Humans; Sudden Unexpected Death in Epilepsy; Research Articles; Tumor Suppressor Proteins; GTPase-Activating Proteins; Electroencephalography; Heart; info:eu-repo/classification/ddc/616.8; Middle Aged; ddc:616.8; 3. Good health; Mutation; Female; Epilepsies, Partial

Objective Germline loss‐of‐function mutations in DEPDC5 , and its binding partners ( NPRL2/3 ) of the mammalian target rapamycin (mTOR) repressor GATOR1 complex, cause focal epilepsies increase risk sudden unexpected death epilepsy (SUDEP). Here, we asked whether haploinsufficiency predisposes to primary cardiac defects that could contribute SUDEP therefore impact clinical management patients at high SUDEP. Methods Clinical investigations were performed 16 with pathogenic variants NPRL2 or NPRL3 . Two novel Depdc5 mouse strains, a human HA‐tagged strain heterozygous knockout neuron‐specific deletion second allele c/− ), generated investigate role activity during seizures. Results Holter, echocardiographic, electrocardiographic (ECG) examinations provided no evidence for altered function patient cohort, whom 3 succumbed 6 had family history There was injury autopsy postmortem case. The revealed expression brain, heart, lungs. Simultaneous electroencephalographic–ECG records on mice showed spontaneous epileptic seizures resulting SUDEP‐like event are not preceded by arrhythmia. Interpretation Mouse data show neither structural nor functional damage might underlie contribution spectrum ‐related epilepsies. ANN NEUROL 2022;91:101–116