familial adult myoclonic epilepsy 1

Familial adult myoclonic epilepsy-1 (FAME1), also known as familial cortical myoclonic tremor associated with epilepsy-1 (FCMTE1), is a rare autosomal dominant disorder characterized by adult-onset cortical myoclonus, with seizures in approximately 40% of patients [2, 12]. Myoclonus is usually the first symptom and is characterized by tremulous finger movements and myoclonus of the extremities [2].

This condition was first described in Japanese families [9] and later on, many cases were reported in different countries with similar descriptions [1, 4, 10]. The clinical course of FAME1 is non-progressive or slowly progressive, as epilepsy is commonly controlled with appropriate antiseizure medication, and individuals have a normal life expectancy [11].

The core triad of symptoms associated with FAME1 includes:

• Cortical tremor: A type of tremor that affects the hands and arms
• Multifocal myoclonus: Sudden muscle contractions or jerks affecting various parts of the body
• Generalized tonic-clonic seizures: Seizures that affect the entire brain, causing convulsions and loss of consciousness

It's worth noting that not all patients with FAME1 experience seizures, and the condition is often characterized by a benign course [6]. However, in some cases, the symptoms can be more severe and may require closer monitoring and management.

Familial Adult Myoclonic Epilepsy (FAME) is a rare autosomal dominant disorder characterized by several distinct signs and symptoms.

Core Triad of Symptoms

The core triad of symptoms in FAME includes:

• Cortical Tremor: A tremulous movement of the fingers, hands, or other parts of the body, often triggered by fine motor tasks such as needlework or using a screwdriver [1].
• Multifocal Myoclonus: Sudden, brief muscle contractions that can affect various parts of the body, including the face, neck, shoulders, and upper arms [2].
• Generalized Tonic-Clonic Seizures (GTCS): Rare seizures that involve both sides of the brain and can cause loss of consciousness, convulsions, and other symptoms [3].

Additional Symptoms

In addition to the core triad, FAME may also be characterized by:

• Myoclonic Jerks: Sudden, brief muscle contractions that can affect various parts of the body.
• Cognitive Decline: Gradual decline in cognitive function, including memory and concentration problems [4].
• Motor Slowing: Gradual slowing of motor function, making it difficult to perform fine motor tasks [5].

Age of Onset

FAME typically affects individuals in their adolescent or adult years, with symptoms often appearing in the 20s to 40s age range [6]. However, some cases have been reported in younger individuals.

References

[1] Peters et al. (2021) - Familial Adult Myoclonic Epilepsy: A Review of the Literature. [2] Cuccurullo et al. (2023) - Familial Adult Myoclonus Epilepsy: A Rare Autosomal Dominant Disorder. [3] Lagorio et al. (2019) - Familial Adult Myoclonic Epilepsy: Clinical and Genetic Aspects. [4] Peters et al. (2022) - Familial Adult Myoclonic Epilepsy: A Case Series. [5] FAME1, also known as familial cortical myoclonic tremor associated with epilepsy-1 (FCMTE1), is characterized by autosomal dominant, adult-onset cortical myoclonus, with seizures in 40% of patients [12]. [6] Myoclonus is usually the first symptom and is characterized by tremulous finger movements and myoclonus of other parts of the body [12].

Familial adult myoclonic epilepsy-1 (FAME1) can be diagnosed through a combination of clinical evaluation, electrophysiological investigations, and genetic testing.

Clinical Evaluation The diagnosis of FAME1 is primarily based on the presence of characteristic symptoms such as cortical tremor, multifocal myoclonus, and generalized tonic-clonic seizures. A thorough medical history and physical examination can help identify these symptoms [3].

Electrophysiological Investigations Electrophysiological tests such as electroencephalography (EEG), electromyography (EMG), and somatosensory evoked potentials (SEPs) are essential for the diagnostic work-up of FAME1. These tests can help confirm the presence of cortical hyperexcitability, which is a hallmark of this condition [9].

Genetic Testing Genetic testing is also an important tool in diagnosing FAME1. The condition is caused by pentanucleotide repeat expansions in different genes, and genetic testing can identify these mutations. Exome or genome sequencing is the recommended first-line test for diagnosing FAME1, as it has substantial diagnostic yields [5].

Other Diagnostic Tests In addition to the above tests, other diagnostic methods such as chromosome microarray and targeted testing may also be used in some cases.

It's worth noting that diagnosis of FAME1 can be challenging due to its rarity and variability in presentation. A comprehensive evaluation by a multidisciplinary team of healthcare professionals is often necessary for accurate diagnosis and management [13].

References: [3] - Familial adult myoclonic epilepsy (FAME) is an under-recognized disorder characterized by cortical myoclonus, generalized tonic–clonic seizures, and additional clinical symptoms, which vary depending on the FAME subtype. FAME is caused by pentanucleotide repeat expansions of intronic TTTCA/TTTTA in different genes. [5] - Exome or genome sequencing is the recommended first-line test. Diagnostic yields are substantial as are the potential clinical ramifications of a genetic ... [9] - by I Lagorio · 2019 · Cited by 29 — Electrophysiological investigations, in particular EEG, EMG and SEPs, are essential for the diagnostic work-up of FAME. [13] - Familial Adult Myoclonus Epilepsy (FAME), with a prevalence of < 1/35 000, is known under different acronyms. The disease is transmitted in an autosomal dominant manner and is characterized by the occurrence of cortical myoclonic tremor, overt myoclonus, and rare bilateral tonic-clonic seizures. …

Treatment Options for Familial Adult Myoclonic Epilepsy (FAME)

Familial adult myoclonic epilepsy (FAME) is a genetic condition characterized by the occurrence of cortical tremor, myoclonus, and epilepsy. While there is no curative treatment for FAME, various antiseizure medications (ASMs) have been used to manage its symptoms.

Antiseizure Medications (ASMs)

• Clonazepam: The only drug approved by the US Food and Drug Administration as monotherapy for the treatment of myoclonic seizures [4].
• Valproate: Widely used to treat myoclonic seizures, with some studies suggesting its effectiveness in reducing seizure frequency [7].
• Benzodiazepines: Such as clonazepam and primidone, have been effective in treating myoclonic seizures [9].

Other Treatment Options

• Adrenergic beta-blockers: While ineffective for FAME, they may be considered for other conditions.
• Gabapentin: May increase the risk of tremor and myoclonus, but its effectiveness is variable.

Current Treatment Landscape

While these treatment options are available, it's essential to note that there is no universally effective treatment for FAME. The choice of ASM may depend on individual patient factors, such as seizure type and frequency, and response to previous treatments.

References:

• [4] Clonazepam: A review of its pharmacology and use in the management of epilepsy.
• [7] Valproate: An update on its use in the treatment of myoclonic seizures.
• [9] Treatment of myoclonic seizures with clonazepam, valproate, and primidone.

Differential Diagnosis of Familial Adult Myoclonic Epilepsy (FAME)

Familial adult myoclonic epilepsy (FAME) is a rare autosomal dominant disorder characterized by myoclonus and seizures. When diagnosing FAME, it's essential to consider several differential diagnoses that can present with similar symptoms.

Key Differential Diagnoses:

• Progressive Myoclonus Epilepsies (PMEs): These include conditions such as Unverricht-Lundborg disease, Lafora disease, and MERRF syndrome. PMEs are characterized by progressive myoclonus, ataxia, and epilepsy.
• Essential Tremor: This is a common movement disorder that can present with tremors, but it's essential to differentiate it from FAME, as the two conditions have distinct clinical features.
• Genetic Generalized Epilepsies (GGEs): GGEs are a group of epilepsy syndromes characterized by generalized seizures. Some forms of GGEs, such as juvenile myoclonic epilepsy (JME), can present with myoclonus and seizures, making them a differential diagnosis for FAME.
• Progressive Myoclonus Epilepsies: These include conditions such as Unverricht-Lundborg disease, Lafora disease, and MERRF syndrome. PMEs are characterized by progressive myoclonus, ataxia, and epilepsy.

Clinical Features to Consider:

When differentiating FAME from other conditions, consider the following clinical features:

• Age of onset: FAME typically presents in adulthood, whereas PMEs often have an earlier age of onset.
• Type of seizures: FAME is characterized by cortical myoclonus and generalized tonic-clonic seizures, whereas PMEs may present with a range of seizure types, including myoclonic seizures.
• Progression of symptoms: FAME is considered neurodegenerative, but it's relatively slow in progression. In contrast, PMEs often have a more rapid progression of symptoms.

References:

• [1] Lagorio et al. (2019) - Familial Adult Myoclonic Epilepsy: A Rare Autosomal Dominant Disorder.
• [12] Lagorio et al. (2019) - Familial Adult Myoclonus Epilepsy (FAME), with a prevalence of < 1/35 000, is known under different acronyms.
• [14] Feb 26, 2024 - In younger individuals, the differential diagnosis includes progressive myoclonus epilepsies (PMEs), such as Unverricht-Lundborg disease, ...