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PubMed This is a summary of 18 peer-reviewed journal articles Updated
Neurology

Reaching a Diagnosis: The Tools That "See" FAME

At a Glance

Familial Adult Myoclonic Epilepsy (FAME) is often misdiagnosed as essential tremor. An accurate diagnosis requires specialized tests like Giant Somatosensory Evoked Potentials (SEPs) to find cortical hyperexcitability, and long-read genome sequencing to identify the hidden genetic mutation.

Getting an accurate diagnosis for Familial Adult Myoclonic Epilepsy (FAME) can be a long journey. Because the symptoms often look like more common movement disorders, many patients are misdiagnosed for decades [1][2]. Understanding the specific tests required to “see” FAME is essential for ensuring you receive the correct care.

Why FAME is Often Missed

The most common misdiagnosis for FAME is Essential Tremor [2]. On the surface, they look similar: both cause hands to shake when you are holding a cup or writing. However, while Essential Tremor is a rhythmic “shaking,” the FAME tremor is actually cortical myoclonus—a series of hundreds of tiny, lightning-fast muscle jerks [3][1].

Because these jerks are so small, many doctors don’t realize they are part of an epilepsy syndrome until a patient has their first convulsive seizure, which often doesn’t happen until decades after the tremor starts [4][5].

Identifying “Cortical Hyperexcitability”

To confirm FAME, doctors look for cortical hyperexcitability. This means the sensory and motor parts of your brain are “over-reacting” to signals [6]. They use two specialized tests to find this:

  • Giant Somatosensory Evoked Potentials (SEPs): In this test, small electrical pulses are sent to the nerves in your wrist, and your brain’s response is recorded [7]. In a person with FAME, the brain’s response is “giant”—it produces an electrical wave much larger than normal because the cortex is hypersensitive [6][8].
  • The C-Reflex: This is an exaggerated motor response. When a nerve is stimulated, the brain sends back a “long-latency” reflex that causes a visible jerk [5]. This “C-reflex” is a hallmark sign that the tremor is coming from the brain’s cortex [9].

The Genetic “Blind Spot”

Standard genetic tests (like “panels” or “short-read sequencing”) often fail to find FAME. This is because these tests break DNA into tiny pieces to read them. Imagine trying to count how many times the word “Wait” is repeated in a 10,000-page book by only looking at one sentence at a time; you would never see the “stutter” [10][11].

To find the FAME mutation, doctors must use Long-Read Genome Sequencing [12][10]. This newer technology can read very long strands of DNA at once, allowing scientists to see the entire “stutter” (the pentanucleotide repeat) and confirm which gene is involved, such as SAMD12 or STARD7 [13][11].

Diagnostic Checklist

If you or your doctor suspect FAME, these are the tests and findings typically used to reach a definitive answer:

  1. Clinical History: Tracking the “triad” (tremor, jerks, and rare seizures) and checking for a family history of similar symptoms [14][3].
  2. SEP (Somatosensory Evoked Potential): Looking specifically for “Giant SEPs” and the C-reflex [8][9].
  3. EEG (Electroencephalogram): Used to monitor brain wave activity. The technician will likely use a strobe light (photic stimulation) during the test to check for sensitivity to flickering lights (photosensitivity) [15][16].
  4. Long-Read Sequencing: The gold-standard genetic test to identify the specific pentanucleotide repeat [12][11].
  5. Standard MRI: Usually performed to rule out other causes, though in FAME, the brain structure often appears normal or shows only very subtle changes [17][18].

Common questions in this guide

Why is FAME often misdiagnosed as essential tremor?
FAME and essential tremor both cause shaky hands, especially when holding objects. However, the FAME tremor is actually caused by hundreds of tiny, rapid muscle jerks called cortical myoclonus, which require specialized testing to properly identify.
What does a 'Giant SEP' test result mean?
A Giant Somatosensory Evoked Potential (SEP) means your brain produces a larger-than-normal electrical wave in response to nerve stimulation. This indicates cortical hyperexcitability, which is a key diagnostic feature of FAME.
Why didn't my standard genetic test detect FAME?
Standard genetic panels read DNA in short fragments, which causes them to miss the long, repeating genetic stutters that cause FAME. To accurately find the FAME mutation, doctors must use a specialized test called long-read genome sequencing.
How is an EEG used to help diagnose FAME?
An EEG monitors your brain wave activity. During the test, technicians will often use a strobe light to check if your brain is overly sensitive to flickering lights, which is a common finding in people living with FAME.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.How do my SEP (Somatosensory Evoked Potential) results compare to the 'giant' patterns typical of FAME?
  2. 2.Was my genetic testing 'short-read' or 'long-read' sequencing, and can we order long-read sequencing to look for repeat expansions?
  3. 3.Do we see evidence of a 'C-reflex' on my neurophysiological tests?
  4. 4.Could my previous diagnosis of Essential Tremor have actually been the 'cortical tremor' associated with FAME?
  5. 5.Does my EEG show any patterns that are common in FAME, especially in response to flickering lights?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (18)
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    Familial adult myoclonic epilepsy: A new expansion repeats disorder.

    Lagorio I, Zara F, Striano S, Striano P

    Seizure 2019; (67()):73-77 doi:10.1016/j.seizure.2019.03.009.

    PMID: 30928698
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    Autosomal dominant cortical tremor, myoclonus and epilepsy.

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    Familial Adult Myoclonic Epilepsy: Clinical and Genetic Approach to an Under-recognized Disease.

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    A Biomarker for Benign Adult Familial Myoclonus Epilepsy: High-Frequency Activities in Giant Somatosensory Evoked Potentials.

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    Amplitude of Somatosensory Evoked Potentials (SEPs) Recorded in Short-Latency SEP Condition Is 80% of That in Giant SEP Condition.

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This page provides educational information about the diagnostic tests and criteria for FAME. Always consult a neurologist or epileptologist to interpret your specific test results and receive an official diagnosis.

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