Abstracts

SCN1A MUTATIONS AND SUDEP IN FAMILIES

Abstract number : 2.093
Submission category : 4. Clinical Epilepsy
Year : 2009
Submission ID : 9810
Source : www.aesnet.org
Presentation date : 12/4/2009 12:00:00 AM
Published date : Aug 26, 2009, 08:12 AM

Authors :
Deepa Sirsi and S. Arnold

Rationale: Sodium channel mutations are implicated in excitatory dysfunction which could result in a wide spectrum of epilepsy syndromes ranging from GEFS+ (Genetic epilepsy febrile seizure plus) to severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome). The mortality rate for patients with Dravet syndrome is very high ranging from 15-20% by the age of 20 years. The common causes are status epilepticus, drowning and SUDEP (sudden unexpected death in epilepsy). There is one published report of familial cases of SUDEP in a GEFS + family with a novel SCN1A mutation. We report 2 patients with novel SCN 1A mutations and family members with SUDEP. We also report 2 novel missense variant SCN 1A mutations in patients with electroclinical features of Dravet syndrome or Severe myoclonic epilepsy broderline(SMEB)and a family history of intractable epilepsy. Methods: Retrospective chart review of pediatric patients with SCN1A mutations at UTSW Medical Center was conducted. Information sought included age at onset of febrile and afebrile seizures, EEG and imaging results, types of seizures and frequency, family history of epilepsy and SCN 1A mutation analysis. Clinical information for SUDEP cases was obtained from next of kin. Results: Table 1 contains clinical information of patients with SCN 1A mutations and SUDEP in family members or family history of intractable epilepsy. The mutations detected include 1 novel predicted disease associated mutation and 3 missense variants. There were 2 patients with cases of SUDEP in family members. Patient 1 in Table 1, had 2 siblings (brother and sister) with epilepsy. The brother's initial seizures at 6 months were febrile seizures and had 2 episodes of convulsive status epilepticus prior to 3 years of age. Subsequently he had frequent GTC seizures. He was found dead while asleep at 16 yrs of age. Post mortem examination was unrevealing. His sister had febrile seizures at 18 months of age. Subsequent seizure types included frequent grand-mal seizures and atonic seizures. She was found dead during a nap at 4 Yrs of age. Post mortem examination was not revealing. In addion, mother and aunt had febrile seizures until 7 yrs of age. A 31 year old cousin has intractable seizures since childhood. Parental testing indicate that the amino acid variant was maternally inherited. Patient 2 had a half brother who started to have intractable seizures after receiving immunizations at 1 year of age. He died at 19 yrs of age of probable SUDEP. The SCN 1A mutation detected was a novel predicted disease associated mutation. Conclusions: Two of the 5 patients in our clinic with Dravet syndrome had a family history of SUDEP, which is not frequently reported. All of the 5 patients decribed above had a family history of febrile seizures or intractable epilepsy (2 of them have a parent with the same mutation) which is also unusual as >90% of SCN1A mutations associated with Dravet syndrome are reported as de novo mutations. Although this could be a selection bias, it may suggest that SCN1A genetic testing could help with counselling patients and their families about the risk for SUDEP.
Clinical Epilepsy