Familial Autosomal Dominant Focal Epilepsies

Question 1

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE)

Answer 1

Men and women are equally affected.

Onset: Mainly in late childhood at 7–12 years of age (mean 11 years),

Semiology: Frequent (almost every night) clusters of brief (20–50 s) nocturnal motor seizures with hyperkinetic/dystonic features and/or tonic manifestations. These hypermotor seizures of ADNFLE are identical to those of the supplementary sensorimotor area (SMA). GTCSs occur in two-thirds of patients and are very infrequent.

Etiology: autosomal dominant disorder. Penetrance is about 70%.. CHRNA4, CHRNB2, which encode the nAChR subunit proteins.

Ictal EEG: ictal frontal discharges or anterior, rhythmic, slow-wave activity in another 47% of patients.

Prognosis: Seizures are lifelong. Attacks may become milder in the fifth or sixth decade of life and be described as fragments of previous seizures.

Treatment: Carbamazepine monotherapy is effective. A third of patients are resistant to treatment.

Question 2

Familial mesial temporal lobe epilepsy

Answer 2

Demographics: unknown

Onset: typically in teenage years and early adult life.

Semiology: Seizures are generally mild, infrequent, and well-controlled with antiepileptic drugs. Simple focal seizures are more common than complex focal seizures. The simple focal seizures consist of déjà vu, fear, numbness, etc. Rising epigastric sensation does not occur in familial MTLE. GTCS are rare.

Autosomal dominant inheritance with 60% penetrance.

Prognosis: typically very good. Many patients don’t even know that they have this disorder, unless other family members are diagnosed.

Treatment: similar to sporadic temporal lobe epilepsy.

Question 3

Familial lateral temporal lobe epilepsy

Answer 3

Onset occurs in teenage years or early adult life.

Mild seizures with mainly auditory hallucinations, mainly nocturnal and infrequent GTCS, excellent response to treatment. Other sensory symptoms such as simple visual, olfactory and vertiginous phenomena are common.

FLTLE is the first non-ion channel familial epilepsy to have been discovered.
FLTLE has autosomal dominant inheritance with high penetrance (about 80%). Mutations of the leucine-rich, glioma-inactivated 1 (LGI1)/epitempin gene on chromosome 10q are responsible for the syndrome.

Prognosis: Excellent. Patients are neurologically and mentally normal.

Question 4

Familial focal epilepsy with variable foci

Answer 4

The age of onset varies markedly from months to 43 years.

Different family members have focal seizures emanating from different cortical locations. Each individual patient has the same electric clinical pattern of single location focal epilepsy. Seizures are often the nocturnal and there’s great intrafamilial friability.

Autosomal dominant inheritance and penetrance of about 60%. DEPC5 mutation has also been associated.

Interictal epileptiform abnormalities occur in most patients. Their locations vary between family members. This discharges are facilitated by sleep.

Prognosis: usually excellent