Graduated clinical manifestations according to mutation type in patients with severe myoclonic epilepsy in infancy

Klaus Brusgaard, Rikke Steensbjerre Møller, Hans Atli Dahl, Helle Hjalgrim

Publikation: Konferencebidrag uden forlag/tidsskriftKonferenceabstrakt til konferenceForskningpeer review


Severe myoclonic epilepsy in infancy (SMEI) is a severe form of generalized epilepsy
with febrile seizures (GEFS+). SMEI is a rare disorder characterized by generalized
tonic, clonic, and tonic-clonic seizures that are initially induced by fever and begin
during the first year of life. Later, patients also manifest other seizure types, including
absence, myoclonic, and simple and complex partial seizures. Psychomotor
development stagnates around the second year of life. SME is considered to be
the most severe phenotype within the spectrum of GEFS+. SME is a malignant
epileptic syndrome, while GEFS+ is usually benign. An autosomal dominant pattern
of inheritance is observed with GEFS+.

SCN1A-related seizure disorders encompass a spectrum that ranges from simple
febrile seizures (FS) and generalized epilepsy with febrile seizures plus (GEFS+) at
the mild end to Dravet syndrome and intractable childhood epilepsy with generalized
tonic-clonic seizures (ICE-GTC) at the severe end

Patients and methods
87 infants representing GEFS+ were analyzed by bidirectional sequencing of all
exons of the SCN1A, SCN2A, GABRG2 or SCN1B genes. Additionally, MLPA
analysis of SCN1A was performed.

In 36 patients with disease causing mutations were characterized. 34 mutations were
found in SCN1A and two in GABRG2. 9 mutations were found in relatives.

The majority of the patients presenting with missense mutations had a less severe
form of GEFS+. In all but one case the mutation positive relatives belong to this
group. The majority of the relatives had no phenotypic manifestations. The patients
with nonsense, splice site or frameshift mutations or large deletions had phenotypes
in the SMEI end of the clinical spectra. All but 2 of the missense mutations were new.
Mutations giving rise to the SMEI phenotype represent de novo incidences.
Antal sider1
StatusUdgivet - 2011
Begivenhed11th International Symposium on Mutations in the Genome 6 - 10 June 2011 Santorini, Greece - Santorini, Grækenland
Varighed: 6. jan. 201210. jan. 2012


Konference11th International Symposium on Mutations in the Genome 6 - 10 June 2011 Santorini, Greece