REVIEW
The progressive myoclonic epilepsies
1
Department of Neurology,
Institute of Neurological
Sciences, Southern General
Hospital, Glasgow, UK
2
Department of Neuropathology,
Institute of Neurological
Sciences, Southern General
Hospital, Glasgow, UK
Correspondence to
Dr N Malek, Department of
Neurology, Southern General
Hospital, Glasgow G51 4TF, UK;
nmalek@nhs.net
Accepted 1 February 2015
To cite: Malek N, Stewart W,
Greene J. Pract Neurol
Published Online First: [ please
include Day Month Year]
doi:10.1136/practneurol-
2014-000994
Naveed Malek,1 William Stewart,2 John Greene1
ABSTRACT
Progressive myoclonic epilepsies are a group of
disorders characterised by a relentlessly
progressive disease course until death; treatment-
resistant epilepsy is just a part of the phenotype.
This umbrella term encompasses many diverse
conditions, ranging from Lafora body disease to
Gaucher’s disease. These diseases as a group are
important because of a generally poor response
to antiepileptic medication, an overall poor
prognosis and inheritance risks to siblings or
offspring (where there is a proven genetic cause).
A correct diagnosis also helps patients and their
families to accept and understand the nature of
their disease, even if incurable. Here, we discuss
the phenotypes of these disorders and
summarise the relevant specific investigations to
identify the underlying cause.
INTRODUCTION
The progressive myoclonic epilepsies
comprise a devastating group of rare dis-
orders that manifest with worsening
action myoclonus; it is also present at rest
but activates with stimuli such as noise,
light or touch.1 Other neurological fea-
tures that frequently but not reliably
coexist include other seizure types ( par-
ticularly generalised tonic–clonic), pro-
gressive ataxia and dementia. Typically,
the presentation is in late childhood or
adolescence; however, they may affect all
ages. Ultimately, patients become wheel-
chair users and have a reduced life expect-
ancy. It may be challenging to distinguish
these conditions very early on from more
common forms of genetic generalised epi-
lepsy, particularly juvenile myoclonic epi-
lepsy. However, features suggesting
progressive myoclonic epilepsy are the
presence or evolution of progressive
neurological disability, failure to respond
to antiepileptic drug therapy and back-
ground slowing on EEGs.2 Many progres-
sive myoclonic epilepsies have similar
clinical presentations yet are genetically
heterogeneous, making accurate diagnosis
difficult. Therein lies the importance of
getting the diagnosis right: if we are to
investigate specific treatments for individ-
ual disorders (eg, gene therapy for Tay–
Malek N, et al. Pract Neurol 2015;0:1–8. doi:10.1136/practneurol-2014-000994
Sachs disease), then it is crucial to get the
diagnosis right.3–6
Unverricht–Lundborg disease
Unverricht–Lundborg disease—also called
progressive myoclonic epilepsy type 1
(EPM1)—is autosomal-recessively inher-
ited and is characterised by stimulus-
sensitive myoclonus and tonic–clonic
seizures. The age of onset is usually 6–16
years. Some years after the disease onset,
patients may develop cerebellar features,
such as ataxia, incoordination, intention
tremor and dysarthria. Individuals with
Unverricht–Lundborg disease are men-
tally alert but show emotional lability,
depression and mild decline in intellec-
tual performance over time.7 EPM1
results from mutations in the CSTB gene
causing defective function of cystatin B, a
cysteine protease inhibitor.8
Lafora body disease
Lafora body disease—also called progres-
sive myoclonic epilepsy type 2 (EPM2)
and named after the Spanish neurologist
Gonzalo Lafora—is an autosomal-recessive
form of progressive myoclonus epilepsy.
It is characterised by myoclonus, tonic–
clonic seizures, visual hallucinations,
intellectual decline and progressive neuro-
logical deterioration.9 The age of onset is
usually 12–15 years, but an earlier onset
variant begins at the age of 5 years.10 11
Lafora body disease is caused by mutations
either in the EPM2A gene (encoding for
laforin, a dual-specificity protein phosphat-
ase) or in the EPM2B (NHLRC1) gene
(encoding malin, an E3- ubiquitin ligase).11
These two proteins interact and, as a
complex, regulate glycogen synthesis.
Lafora body disease is, therefore, a dis-
order of carbohydrate metabolism resulting
in polyglucosan inclusion bodies in neural
and other tissues.12
Tissue biopsy (axillary skin) reveals
Lafora bodies, which are aggregates of poly-
glucosans (poorly constructed glycogen
molecules). Lafora bodies are pathogno-
monic and do not occur in any other
condition.
1
 REVIEW
Action myoclonus renal failure syndrome
Action myoclonus renal failure (AMRF) syndrome—
also called progressive myoclonic epilepsy type 4
(EPM4)—is a distinctive form of progressive myoclonus
epilepsy associated with renal dysfunction.13 It is an
autosomal-recessive disease related to loss-of-function
mutations in SCARB2 gene.14 The onset is in the second
and third decades, but there is also a late-onset form,
starting in the fifth and sixth decades and without renal
failure.15 16 AMRF shows genotype–phenotype hetero-
geneity, such that affected people within the same
sibship, despite identical gene mutations, can present
differently: some with neurological features while others
with renal impairment.17
PRICKLE1-gene-related progressive myoclonic epilepsy
with ataxia
PRICKLE1-gene-related progressive myoclonic epi-
lepsy—also called progressive myoclonic epilepsy type
5 (EPM5)—is characterised by myoclonic seizures,
generalised tonic–clonic seizures (often sleep-related)
and ataxia, but with normal cognition. The age of
onset is 5–10 years. Action myoclonus may affect the
limbs or bulbar muscles, sometimes with spontaneous
myoclonus of facial muscles causing marked dysarth-
ria.18 PRICKLE proteins, such as PRICKLE1, are core
constituents of the planar cell polarity-signalling
pathway that establishes cell polarity during embry-
onic development.19
‘North Sea’ progressive myoclonus epilepsy
‘North Sea’ progressive myoclonus epilepsy—also
called progressive myoclonic epilepsy type 6 (EPM6)
—is characterised by ataxia starting around aged
2 years and followed by myoclonic seizures when
aged 6–7 years. Patients have multiple seizure types,
including generalised tonic–clonic seizures, absence
seizures and drop attacks. Most patients develop scoli-
osis by adolescence: an important diagnostic clue.
There may also be skeletal deformities, including pes
cavus and syndactyly. The condition is caused by
mutations in the Golgi SNAP receptor complex 2
gene (GOSR2).20 Patients have elevated serum creatine
kinase concentrations (median ≈700 IU) in the
context of a normal muscle biopsy.21
Myoclonic epilepsy with ragged-red fibres
Myoclonic epilepsy with ragged-red fibres (MERRF)
is a multisystem mitochondrial disorder, named after
its characteristic muscle biopsy appearances (figure 1).
The onset is usually in childhood, after normal early
development. The first symptom is often myoclonus,
followed by generalised epilepsy, ataxia, weakness and
dementia. Common associated findings are hearing
loss, short stature, optic atrophy and cardiomyopathy
with Wolff–Parkinson–White syndrome. Some patients
have pigmentary retinopathy and/or lipomatosis.22
2 Malek N, et al. Pract Neurol 2015;0:1–8. doi:10.1136/practneurol-2014-000994
Myoclonus does not occur in all mitochondrial dis-
eases (3.6% of 1086 patients in one study) but is prom-
inent in MERRF.23 Their myoclonus is not inextricably
linked to epilepsy, but more so to cerebellar ataxia.23
MERRF is most commonly caused by a mutation in the
tRNALys gene in mitochondrial DNA at nucleotide pos-
ition 8344, leading to altered mitochondrial function,
but there are also other point mutations.24 25
Neuronal ceroid lipofuscinoses
The neuronal ceroid lipofuscinoses (CLN) comprise a
heterogeneous group of inherited, neurodegenerative,
lysosomal storage disorders characterised by progres-
sive cognitive and motor deterioration, progressive
tonic–clonic as well as myoclonic seizures, and early
death. Most forms have visual loss.26 The clinical phe-
notypes traditionally divide into infantile, late infant-
ile, juvenile and adult, based on age at onset.
However, a new classification system takes into
account both the gene involved (genes designated
with CLN loci from 1 to 14) and the age at disease
onset; for example, (CLN1 disease, infantile onset)
and (CLN1 disease, juvenile onset) are both caused by
mutations in PPT1 but with differing age of onset,
and with considerable phenotype–genotype hetero-
geneity (table 1).26 These are usually autosomal reces-
sive but there are also autosomal-dominant late-onset
forms.27 In childhood, the neuronal CLN are the
most common lysosomal diseases and the most
common neurodegenerative diseases, but, in adults,
they represent a small fraction of the neurodegenera-
tive diseases.28 The adult type (Kufs’ disease) is the
rarest of all the subtypes of neuronal CLN. The
pathological findings on biopsy are abnormal auto-
fluorescent lipopigments from lysosomal inclusion
bodies deposited in brain, myenteric plexus, muscle
and skin. Electron microscopy has a special role in
their diagnosis. The characteristic ultrastructural
abnormalities in neuronal CLN, seen in conveniently
available biopsy specimens (skin) or lymphocytes
(buffy coat), include one (or a combination) of
Figure 1 A ragged-red fibre in a muscle biopsy specimen (top
left) on the Gomori trichome stain.
 REVIEW
Table 1 Neuronal ceroid lipofuscinosis (CLN) loci and genotype–phenotype correlations with characteristic electron microscopy
findings in biopsy samples
Locus Age of onset (phenotype) Gene Electron microscopy
CLN1 Infantile, late infantile, juvenile, adult (Kufs’ disease) PPT1 Granular osmophilic deposits
CLN2 Late infantile, juvenile TPP1 Curvilinear profiles
CLN3 Adult (Kufs’ disease) CLN3 Fingerprint profiles
CLN4 Adult (Parry’s disease) DNAJC5 Granular osmophilic deposits, mixed
CLN5 Late infantile CLN5 Fingerprint profiles
CLN6 Late infantile, adult (Kufs’ disease) CLN6 Curvilinear profiles, fingerprint profiles, Rectilinear complex
CLN7 Late infantile MFSD8 Curvilinear profiles, fingerprint profiles, rectilinear complex
CLN8 Late infantile (Northern epilepsy) CLN8 Curvilinear profiles or granular osmophilic deposits
CLN9 Juvenile Unknown Granular osmophilic deposits, curvilinear profiles
CLN10 Congenital CTSD Granular osmophilic deposits
CLN11 Adult (Kufs’ disease) GRN Fingerprint profiles
CLN12 Juvenile ATP13A2 Granular osmophilic deposits, mixed
CLN13 Adult (Kufs’ disease) CTSF Fingerprint profiles or none
CLN14 Infantile KCTD7 Granular osmophilic deposits, fingerprint profiles
Adapted from ref. 30.
Mixed indicates curvilinear profiles, fingerprint profiles, rectilinear complex and granular osmophilic deposits.
PPT-1, palmitoyl-protein thioesterase 1; TPP-1, tripeptidyl peptidase 1.

fingerprint, curvilinear and membranous profile inclu-
sions in the lysosomes (table 1).29
Dentatorubral-pallidoluysian atrophy
Dentatorubral-pallidoluysian atrophy (DRPLA), unlike
other progressive myoclonus epilepsies, is an
autosomal-dominant disorder characterised by epi-
lepsy, cerebellar ataxia, choreoathetosis, myoclonus,
dementia and psychiatric symptoms in varying combi-
nations. DRPLA is caused by an unstable expansion of
CAG repeats in exon 5 of the DRPLA gene on
chromosome 12, coding for polyglutamine tracts.
Being a trinucleotide repeat disorder, it also shows the
phenomenon of anticipation, with paternal transmis-
sion resulting in more prominent anticipation than
maternal transmission. DRPLA protein (also called
atrophin-1) is located in the nucleus and functions as
a transcription coregulator.31 Patients with a
progressive myoclonic epilepsy phenotype have larger
expansions (62–79 repeats) and earlier age of onset
(before aged 20 years) while those with a non-
progressive myoclonic epilepsy phenotype have a later
age of onset (after aged 20 years) and smaller expan-
sions (54–67 repeats).32
Sialidosis type 1 (cherry-red spot myoclonus syndrome)
Sialidosis, also called mucolipidosis type I, is an
autosomal-recessive lysosomal storage disease caused
by a deficiency of the enzyme α-N-acetyl
neuraminidase-1 (coded by the NEU1 gene on
chromosome 6p21). It is classified into two main clin-
ical variants: type 1, the milder variant, and type 2,
usually more severe and with an earlier onset.33 The
disease is characterised by myoclonic epilepsy, visual
problems, hyperreflexia and ataxia that develop in the
second or the third decade of life.34 Although patients
with sialidosis always have macular cherry-red spots
(figure 2), this is not a pathognomonic finding since
they also occur in central retinal artery occlusion and
metabolic storage diseases such as Tay–Sachs disease,
Sandhoff ’s disease, Niemann–Pick disease, Fabry’s
disease and Gaucher’s disease, some of which can also
have a progressive myoclonic epilepsy phenotype.35
The characteristic pathology of sialidosis reflects tissue
accumulation and urinary excretion of sialylated
oligosaccharides.36

GM2 gangliosidosis (Tay–Sachs disease and variants)

The GM2 gangliosidoses comprise a group of
autosomal-recessive disorders characterised by accu-
mulation of GM2 ganglioside, one type of glycolipid,
Figure 2 A cherry-red spot in the macula on a fundus in neuronal cells. The genes responsible for these dis-
photograph from the left eye. orders are HEXA (Tay–Sachs disease and variants),

Malek N, et al. Pract Neurol 2015;0:1–8. doi:10.1136/practneurol-2014-000994 3

 REVIEW
HEXB (Sandhoff ’s disease and variants) and GM2A
(AB variant of GM2 gangliosidosis).37 The proteins
encoded by these three genes are the α-subunits
(HEXA gene) and β-subunits (HEXB gene) of
β-hexosaminidase A enzyme. The third is a small gly-
colipid transport protein, the GM2 activator protein
(GM2A), which acts as a substrate specific cofactor
for the enzyme. A deficiency of any one of these pro-
teins leads to storage of the ganglioside, primarily in
the lysosomes of neuronal cells, causing cell death.38
The three subtypes are clinically indistinguishable
apart from subtle visceral and skeletal manifestations
in some people with Sandhoff ’s disease.39 The most
severe early onset form of Tay–Sachs disease is charac-
terised by a progressive and relentless neuronal dys-
function, manifesting as hypotonia, blindness,
dementia, seizures and subsequently death, usually by
aged 3–5 years.40 Late-onset GM2 gangliosidosis
shows a wide range of symptoms, including cerebellar
ataxia, dystonia, motor neurone disease, psychiatric
symptoms, dementia and rarely polyneuropathy.41
Gaucher’s disease
Gaucher’s disease is the most prevalent lysosomal
storage disease and is caused by >200 mutations that
produce abnormal glucocerebrosidase.42 Gaucher’s
disease can have several phenotypes, ranging from a
perinatal lethal form to an asymptomatic type.43
There are three major clinical phenotypes (1, 2 and
3). Only types 2 and 3 involve the central nervous
system and are distinguished by age at onset and the
rate of disease progression, but these distinctions are
not absolute. Type 3 cases can cause several neuro-
logical impairments, including a horizontal gaze
abnormality, progressive dementia, generalised epi-
lepsy, ataxia and spasticity but also a progressive myo-
clonic epilepsy phenotype.44
Figure 3 Giant somatosensory-evoked N20/P22 potentials at
the central scalp (Cc) electrode on the left side, with normal
somatosensory-evoked potentials from another person on the
right side. Fc, Fz, Fi, Cc and Cz refer to scalp electrode
positions.
4 Malek N, et al. Pract Neurol 2015;0:1–8. doi:10.1136/practneurol-2014-000994
NEUROPHYSIOLOGY
Not all progressive myoclonic epilepsies have well-
characterised neurophysiological findings, but we shall
describe those of the most common disorders. Lafora
body patients’ EEGs show varying degrees of slowing
of background activity (in the vast majority), general-
ised epileptiform discharges (in 85%), focal discharges
(in about a third) and photosensitivity to a
fast-frequency stimulus (in a quarter). About two-thirds
of patients show giant somatosensory-evoked poten-
tials (14–175 mV) (figure 3).45
In Unverricht–Lundborg disease, the scalp EEG
shows generalised epileptiform discharges in the
majority of patients; about half of the patients show
giant somatosensory-evoked potentials.45 In MERRF,
EEG in about two-thirds of patients shows slowing
of background activity with/without generalised
epileptiform discharges; a minority show giant
somatosensory-evoked potentials. There may be coex-
istent neuropathy or myopathy.45
In neuronal CLN, EEG shows varying degrees of
diffuse slowing of background activity (in 95%) and
generalised epileptiform discharges (in 80%); about a
quarter of patients show giant somatosensory-evoked
potentials. Nerve conduction studies show evidence of
axonal neuropathy in about 30% of patients.45
Diagnostic testing
Investigations should be directed towards the pheno-
type that best fits the patient’s condition; however,
the clinical phenotypes of the progressive myoclonic
epilepsies overlap sufficiently such that it is not pos-
sible to make a definitive clinical diagnosis of individ-
ual disorders, and hence the reliance on laboratory,
genetic and ancillary investigations. Some of the pro-
gressive myoclonic epilepsies are metabolic disorders
such as Gaucher’s disease and Tay–Sachs disease, and
these can be diagnosed with white cell enzyme ana-
lysis; other conditions such as Lafora body disease
and the neuronal CLN have characteristic histopatho-
logical findings on skin biopsy. Others such as AMRF
syndrome and DRPLA can be diagnosed only with
genetic tests (table 2).
TREATMENT
There are specific treatments for some forms of pro-
gressive myoclonus epilepsy. For example, metabolic
disorders such as Gaucher’s disease may respond to
substrate reduction therapy or enzyme replacement
therapy. Enzyme replacement therapy is now consid-
ered the gold standard for the management of
Gaucher’s disease type 1 and for the non-neurological
manifestations of Gaucher’s disease type 3.46 For con-
ditions where there is no specific therapy, such as
Gaucher’s disease type 2, clinicians can offer only
symptom treatment with antiepileptic drugs to control
seizures.
 REVIEW

Table 2 The investigative workup for progressive myoclonic epilepsies

Disorder Investigations
1. Unverricht–Lundborg disease (EPM1) Gene test: EPM1 (CSTB) mutation analysis
2. Lafora body disease (EPM2) 1. Skin biopsy: Lafora bodies
2. Gene tests: EPM2A or EPM2B (NHLRC1) mutation analysis
3. Action myoclonus renal failure syndrome (EPM4) Gene test: SCARB2/LIMP2 mutation analysis
4. PRICKLE1-related progressive myoclonus epilepsy with Gene test: PRICKLE1 mutation analysis
ataxia (EPM5)
5. ‘North Sea’ progressive myoclonus epilepsy (EPM6) Gene test: GOSR2 mutation analysis
6. MERRF 1. Plasma lactate, pyruvate (as screen)
2. Muscle biopsy: for ragged-red fibres
3. Gene test: MT-TK mutation analysis
7. Neuronal ceroid lipofuscinosis (CLN) 1. Skin biopsy (electron microscopy): curvilinear profiles, fingerprint profiles, granular
osmophilic deposits
2. Leucocyte enzyme analysis (PPT1,TPP1, CTSD)
3. Gene tests: PPT1, TPP1, CLN3, CLN5, CLN6, MFSD8, CLN8, CTSD, DNAJC5, CTSF,
ATP13A2, GRN, KCTD7 mutation analysis
8. DRPLA Gene test: DRPLA mutation analysis
(CAG repeats)
9. Sialidosis type I 1. Sialo-oligosaccharides in urine
(cherry-red spot myoclonus syndrome) 2. Leucocyte enzyme analysis (neuraminidase)
3. Gene test: NEU1 mutation analysis
10. Tay–Sachs disease (GM2 gangliosidosis) 1. Leucocyte enzyme analysis (hexosaminidase A, B)
2. Gene test: HEXA mutation analysis

11. Gaucher’s disease 1. Leucocyte enzyme analysis (β-glucocerebrosidase)

2. Gene test: GBA mutation analysis
DRPLA, dentatorubral-pallidoluysian atrophy; EPM, progressive myoclonus epilepsy.

Valproate is often the first choice to treat myoclonic myoclonic epilepsies, the combination of valproate,
seizures because of its broad spectrum of antiepileptic clonazepam and phenobarbital was superior to con-
action and its good myoclonus suppression potential. ventional antiepileptic drugs such as phenytoin,
It may be less preferable in women owing to its terato- carbamazepine, primidone and diazepam.49 In fact,
genicity but should not be denied to women who clonazepam is the only drug approved by the US
have no plans to conceive, in the face of an incurable Food and Drug Administration as monotherapy for
disease. The rationale for using valproate to treat the treatment of myoclonic seizures,50 but clobazam
myoclonus in progressive myoclonic epilepsies is can be used for brief periods to control seizure clus-
based on trials of its efficacy in juvenile myoclonic ters. Levetiracetam and topiramate are also highly
epilepsy, a myoclonic epilepsy with a comparatively effective for myoclonic seizures and are often used in
benign prognosis.47 Sometimes valproate alone cannot combination or as second-line treatment. On the
achieve seizure control. Also, valproate should be other hand, some antiepileptic drugs may exacerbate
avoided in MERRF due to concerns about liver failure or even induce myoclonus51 and clearly should be
when used in patients with other mitochondrial disor- avoided, particularly sodium channel blockers (carba-
ders.48 In a small trial of 26 adults with progressive mazepine, oxcarbazepine) and GABAergic drugs (tia-
gabine, vigabatrin), as well as gabapentin and
pregabalin.7
Lamotrigine does not appear to be useful in pro-
Table 3 Antiepileptic drugs that may be useful in progressive
gressive myoclonic epilepsies due to poor efficacy,
myoclonic epilepsies (on left) and drugs that may worsen
myoclonus (on the right) dose-related exacerbation of myoclonus and putative
late-onset worsening.52 Lamotrigine also may exacer-
Drugs useful in progressive Drugs that exacerbate bate myoclonus in non-progressive myoclonic epilepsy
myoclonic epilepsies myoclonus
seizure states.53 54 The evidence for levetiracetam,
Sodium valproate* Lamotrigine topiramate and zonisamide in progressive myoclonic
Levetiracetam Phenytoin epilepsies comes from case series; these drugs may
Topiramate Carbamazepine reduce myoclonus besides their efficacy in treating
Clonazepam Oxcarbazepine generalised tonic–clonic seizures.55–57
Zonisamide Tiagabine Finally, high-dose piracetam has been found to be
Phenobarbital Vigabatrin useful in the treatment of progressive myoclonic epi-
*Avoid valproate in myoclonic epilepsy with ragged-red fibres. lepsies58 (table 3).

Malek N, et al. Pract Neurol 2015;0:1–8. doi:10.1136/practneurol-2014-000994 5

 REVIEW
Table 4 Some take home points from this review
Hint Consider
If there is deafness, cardiac problems, optic atrophy, MERRF
short stature or lipomas
If the disease onset is between 5 and 15 years after Lafora body
normal early development, with visual hallucinations disease
(occipital seizures) and normal fundi
If there is a macular cherry-red spot in addition to the Sialidosis
myoclonus and sialo-oligosaccharides in urine
If there is associated renal failure and/or family AMRF
members have renal failure
If phenotype and family history suggest an DRPLA
autosomal-dominant inheritance and anticipation
AMRF, action myoclonus renal failure syndrome, DRPLA,
dentatorubral-pallidoluysian atrophy; MERRF, myoclonic epilepsy with
ragged-red fibres.
Despite all of the available antiepileptic drugs, clini-
cians should recognise a risk of overmedication in
treating drug-resistant myoclonus. Generalised convul-
sive seizures are often part of the phenotype of the
progressive myoclonic epilepsies and these are well
controlled with classic antiepileptic drugs, whereas
myoclonus—which can be the most disabling
symptom resulting in the patient becoming wheelchair
user—is usually refractory to standard antiepileptic
drugs.59 It may be that the drug-resistant myoclonus is
subcortical in origin.60
Progressive myoclonic epilepsies as a group are not
amenable to surgical resection. Vagus nerve stimulation
can help control epileptic seizures and status epilepticus,
but will not help the myoclonus or cerebellar symptoms,
and has no effect on cognitive impairment.61
PROGNOSIS
The prognosis of this group of epilepsies is poor in terms
of seizure control with antiepileptic drugs; however, the
natural histories of the individual disorders vary. In the
most devastating disorders, such as Lafora body disease,
there is a progressive neurological deterioration begin-
ning in adolescence, leading to a vegetative state in status
myoclonicus and death within 10 years9 (table 4).
FUTURE DIRECTIONS
There are some forms of progressive myoclonic epi-
lepsies that have yet to be clinically and genetically
characterised. Although the progressive myoclonic
epilepsies as a group may perhaps be the rarest of the
inherited epilepsies, recent molecular genetic advances
are unravelling the causes of previously nebulous
entities such as AMRF syndrome. In time, the pro-
gressive myoclonic epilepsies may well become the
best understood of the epilepsies at the cellular level,
with the promise of specific treatments.
Acknowledgements We thank Dr Graeme Williams, Consultant
Neuro-ophthalmologist, Institute of Neurological Sciences,
Glasgow, for the image of cherry-red spot in the retina.
Contributors All authors contributed equally to the paper.
Competing interests None.
6 Malek N, et al. Pract Neurol 2015;0:1–8. doi:10.1136/practneurol-2014-000994
Provenance and peer review Not commissioned; externally
peer reviewed. This paper was reviewed by Reetta Kälviäinen,
Kuopio, Finland.
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