Benign adult familial myoclonic epilepsy (ORPHA:86814)
Benign adult familial myoclonic epilepsy (BAFME) is an inherited epileptic syndrome characterized by cortical hand tremors, myoclonic jerks and occasional generalized or focal seizures with a non-progressive or very slowly progressive disease course, and no signs of early dementia or cerebellar ataxia.
Epidemiology
Worldwide prevalence is unknown but an estimated prevalence of 1/35,000 was reported in Japan.
Clinical description
BAFME usually presents in the second decade of life (but age of onset can range from age 11-50) with a minor cortical hand tremor. The tremor consists of continuous, arrhythmic fine twitching in the hands that is exacerbated by fatigue or emotional stress. There is no progression of severity in these tremors until after the age of 70. Myoclonus usually appears around the same age as the cortical tremor and consists of erratic, arrhythmic, segmental jerks of the upper limbs heightened by posture and action. Rare tonic-clonic seizures are also a manifestation of BAFME (peak age of onset being 30), occurring after the appearance of tremors and myoclonus and often precipitated by photic stimulation, emotional stress and sleep deprivation. Some patients from families mapped on chromosome 2p11.1-q12.2 present with drug-resistant complex partial seizures and focal EEG abnormalities. At an advanced age, a worsening of the myoclonus is possible as well as difficulty walking and mild ataxia.
Etiology
BAFME has been mapped to at least 4 different chromosomal loci. The identified chromosomal loci linked to BAFME are: 8q23.3-q24.11 in Japanese families (BAFME type 1), 2p11.1-q12.2 in Italian families (BAFME type 2), 5p15.31-p15.1 in a French family (BAFME type 3) and 3q26.32-q28 in a Thai family (BAFME type 4). In addition, a consanguineous Egyptian family with focal epilepsy, neuropsychiatric features, borderline cognitive level, and myoclonus, resembling BAFME but inherited in an autosomal recessive manner was recently described. A homozygous deletion in the CNTN2 (1q32.1) gene encoding contactin 2 was found to be responsible.
Diagnostic methods
Diagnosis is based on clinical and electrophysiological findings. Electroencephalographic (EEG) findings include a photomyoclonic response along with abnormality of polyspikes and waves. Patients also display extremely enlarged cortical components of somatosensory evoked potentials and an enhanced C-reflex. Jerk-locked average analysis reveals positive-negative, biphasic spikes preceding myoclonus.
Differential diagnosis
BAFME must be differentiated from epilepsy syndromes with prominent myoclonus features. Patients may easily be misdiagnosed as having juvenile myoclonic epilepsy (JME; see this term) due to the occurence of myoclonic jerks and generalized tonic-clonic seizures. However, JME differs clinically from BAFME by the absence of cortical tremor, the mainly proximal myoclonic jerks, and seizures typically occurring at awakening. The absence of ataxia and dementia, the adult onset, and the usually benign outcome of epilepsy differentiates BAFME from progressive myoclonic epilepsies.
Genetic counseling
BAFME is transmitted autosomal dominantly and penetrance is high. Genetic counseling is possible when a family member has the disease and presymptomatic diagnosis may be done in young patients from families mapped on any of the 3 loci, based on electrophysiological findings.
Management and treatment
Cortical tremor (unlike essential tremor) usually has a poor response to beta blockers but improves with antiepileptic drugs. As alcohol aggravates these tremors, it should be avoided. Valproate, levetiracetam, and benzodiazepines are most beneficial in the treatment of cortical tremors and myoclonus due to their combined antiepileptic and antimyoclonic effects. In some cases, epilepsy may be difficult to treat.
Prognosis
BAFME has no effect on life expectancy. With successful treatment, patients are often relieved from their symptoms.

                            Last update: 
                            February 2012


                            - Expert reviewer(s): 
                            Dr Pasquale STRIANO