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Epilepsy, familial adult myoclonic, 3(FAME3; FCMTE3)

MedGen UID:
462210
Concept ID:
C3150860
Disease or Syndrome
Synonyms: CORTICAL MYOCLONIC TREMOR WITH EPILEPSY, FAMILIAL, 3; FAME3
 
Gene (location): MARCHF6 (5p15.2)
 
Monarch Initiative: MONDO:0013322
OMIM®: 613608

Definition

Familial adult myoclonic epilepsy-3 (FAME3) is an autosomal dominant neurologic disorder characterized by onset of cortical tremor, mainly affecting the hands and voice, between 10 and 40 years of age, with adult onset being more common. Most affected individuals develop epilepsy with generalized tonic-clonic seizures; some may have partial or absence seizures. The disorder is nonprogressive or slowly progressive, and most patients respond to antiseizure medication (summary by Florian et al., 2019). For a phenotypic description and a discussion of genetic heterogeneity of familial adult myoclonic epilepsy, see FAME1 (601068). [from OMIM]

Clinical features

From HPO
Myoclonus
MedGen UID:
10234
Concept ID:
C0027066
Finding
Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Bilateral tonic-clonic seizure
MedGen UID:
141670
Concept ID:
C0494475
Sign or Symptom
A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
Focal-onset seizure
MedGen UID:
199670
Concept ID:
C0751495
Disease or Syndrome
A focal-onset seizure is a type of seizure originating within networks limited to one hemisphere. They may be discretely localized or more widely distributed, and may originate in subcortical structures.
EEG with photoparoxysmal response
MedGen UID:
765735
Concept ID:
C3552821
Finding
EEG abnormalities (epileptiform discharges) evoked by flashing lights or black and white striped patterns.
Enhancement of the C-reflex
MedGen UID:
765738
Concept ID:
C3552824
Finding
Increase in amplitude of a long-loop response upon somatosensory evoked potential testing, representing an electrically evoked myoclonic response.
Jerk-locked premyoclonus spikes
MedGen UID:
765739
Concept ID:
C3552825
Finding
Jerk-locked averaging (JLA) is used to record the timing and distribution of brain activity preceding brisk involuntary movements such as those observed in patients with myoclonus. JLA is capable of revealing a premyoclonus spike in the absence of paroxysmal activity in the routine EEG.
Giant somatosensory evoked potentials
MedGen UID:
813291
Concept ID:
C3806961
Finding
An abnormal enlargement (i.e. increase in measured voltage) of somatosensory evoked potentials.

Recent clinical studies

Diagnosis

Magnin E, Vidailhet M, Ryff I, Ferreira S, Labauge P, Rumbach L
J Neurol 2012 Dec;259(12):2714-9. Epub 2012 Jun 27 doi: 10.1007/s00415-012-6575-6. PMID: 22736081

Clinical prediction guides

Florian RT, Kraft F, Leitão E, Kaya S, Klebe S, Magnin E, van Rootselaar AF, Buratti J, Kühnel T, Schröder C, Giesselmann S, Tschernoster N, Altmueller J, Lamiral A, Keren B, Nava C, Bouteiller D, Forlani S, Jornea L, Kubica R, Ye T, Plassard D, Jost B, Meyer V, Deleuze JF, Delpu Y, Avarello MDM, Vijfhuizen LS, Rudolf G, Hirsch E, Kroes T, Reif PS, Rosenow F, Ganos C, Vidailhet M, Thivard L, Mathieu A, Bourgeron T, Kurth I, Rafehi H, Steenpass L, Horsthemke B; FAME consortium, LeGuern E, Klein KM, Labauge P, Bennett MF, Bahlo M, Gecz J, Corbett MA, Tijssen MAJ, van den Maagdenberg AMJM, Depienne C
Nat Commun 2019 Oct 29;10(1):4919. doi: 10.1038/s41467-019-12763-9. PMID: 31664039Free PMC Article
van Rootselaar AF, Groffen AJ, de Vries B, Callenbach PMC, Santen GWE, Koelewijn S, Vijfhuizen LS, Buijink A, Tijssen MAJ, van den Maagdenberg AMJM
Neurology 2017 Dec 5;89(23):2341-2350. Epub 2017 Nov 10 doi: 10.1212/WNL.0000000000004709. PMID: 29127138

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