Paroxysmal dyskinesias

Earliest descriptions: Reported as epilepsy

Although is often credited with the first report of movement-induced seizures, it is possible that his cases actually represented PXD. One of his patients was a boy whose attack lasted 15 seconds, but the boy was said to be unconscious during his initial attack. Later, he remained awake during the attacks. Another patient was a girl whose attacks started at the age of 11 years and occurred when she arose suddenly after prolonged sitting. But at least one of her attacks was said to be associated with a terrified expression, flushed facies, and dilated pupils. After Gowers, a number of reports of “movement-induced seizures” appeared in the literature. Many of these reports have been published under the designation of reflex epilepsy and tonic seizures induced by movement. However unlike most motor convulsions, there was no alteration in the state of consciousness. Moreover, some of these reports had more than tonic contraction, namely, they included sustained twisting, athetosis, and chorea. These characteristics are today referred to as paroxysmal dystonia and paroxysmal choreoathetosis, rather than convulsive seizures. Even the presence of choreoathetosis did not lead the earliest interpreters of these brief attacks to conclude they were a movement disorder; instead, they were considered to be a form of epilepsy, the cerebral site of these “seizures” being in the basal ganglia or in the subcortical region.

After the report of Gowers, the next report of movement-induced paroxysmal movements appears to be that of Spiller in 1927. Spiller described two patients with brief tonic spasms that were brought on by voluntary movement of the involved limbs and, in one of them, also by passive manipulation. Spiller called this “subcortical epilepsy.” described a 5-year-old boy who had brief attacks of unilateral torsion and tonic spasm that lasted up to 3 minutes and were precipitated by fright or excitement. There was no loss of consciousness. The attacks could be preceded by pain. Wilson considered this to be reflex tonic epilepsy and thought it also to be subcortical in origin. The concept that these attacks of tonic, often twisting, contractions without loss of consciousness are uncommon seizure disorders was continued ( ; ). It would appear that today these movement-induced involuntary movements would be considered paroxysmal choreoathetosis/dystonia rather than convulsive movements of the reflex epilepsy type. Differentiation of the attacks between cortical seizures and PXDs is sometimes difficult. Clouding of consciousness, if it occurs, would point to a seizure disorder.

By 1966 and 1967, when papers using the term “paroxysmal choreoathetosis” began regularly to appear ( ; ; ), particularly those cases induced by movements, there were still occasional papers referring the condition to a seizure disorder. As is discussed in the section on paroxysmal hypnogenic dyskinesias PHDs, nocturnal epilepsy is now considered to be the leading cause for that specific entity.

Reported as a paroxysmal disorder of involuntary movements

In 1940, introduced a new concept, that of labeling attacks of tonic spasms plus choreic and athetotic movements as a paroxysmal type of movement disorder. They described a 23-year-old man who had experienced both large and small “spells” since infancy. Both types were preceded by a sensory aura of tightness in parts of the body or by a feeling of tiredness. The movements involved the arms and legs and were usually a combination of sustained twisted posturing and chorea and athetosis. The small attacks lasted from 5 to 10 minutes. Longer attacks were considered large and also involved the neck (retrocollis), eyes (upward gaze), face (ipsilateral to the limbs if the limb involvement was unilateral), and speech. These large attacks lasted for as long as 2 hours, and the movements were considered to resemble those seen in Huntington disease. There was never a loss of consciousness or clonic convulsive movements, biting of the tongue, or loss of sphincter control. Drinking alcohol, coffee, tea, or cola would usually bring on an attack. Fatigue, smoking, and concentrating were other precipitating factors. The attacks would clear more rapidly if the patient would lie down and would be aborted by sleep. The patient had an average of one large and two small attacks a day. Between attacks, the neurologic examination was normal. Phenytoin and phenobarbital had no effect, and scopolamine was the only drug found to reduce the frequency, severity, and duration of the attacks. The family history revealed 27 other members who had similar attacks; the pedigree showed autosomal dominant inheritance with what appears to be complete penetrance. called this disorder “familial paroxysmal choreoathetosis.”

Mount and Reback’s paper (1940) became the seminal paper in the field of PXDs. After its publication, most of the reports in the literature referenced it over the next five decades. However, the next report of a large family with similar attacks of muscle spasms did not refer to it. In 1961, Forssman described a family with autosomal dominant inheritance in which there were attacks lasting from 4 minutes to 3 hours.

The next large family was described in 1963 by . Like , Lance also did not relate this to nor refer to Mount and Reback’s report, nor did he mention the report by Forssman. In fact, Lance considered his patients to have a form of epilepsy. Later, was to write one of the definitive papers in this field, containing a useful classification scheme in which he related his family to those of , , and .

Although there were reports of patients whose PXDs were induced by sudden movement, they were not denoted by any special terminology until 1967, when introduced the label “paroxysmal kinesigenic choreoathetosis” (PKC). This label has developed into a most useful and widely accepted designation because the kinesigenic feature has proven to be so characteristic. Kinesigenicity has an important place in the classification of the PXDs, and Demirkiran and Jankovic (1995) recommended that the term “paroxysmal kinesigenic dyskinesia” (PKD) be used instead, because the movements can be other than choreoathetotic. That suggestion is followed in this chapter. As is pointed out later, the PKD designation can be applied to some patients who do not have the dyskinesias triggered by sudden movement (or startle).

Kertesz (1967) reported 10 new cases of PXD and reviewed the literature. Among the important features of his paper, Kertesz differentiated the kinesigenic variety (induced by sudden movement) from that described by Mount and Reback, by Forssman, and by Lance, which were aggravated not by movement but by alcohol, caffeine, and fatigue. (It should be noted that Kertesz differentiated the kinesigenic type from that reported by and by , but he failed to mention the paper by .)

Although phenytoin was recognized earlier as a very useful agent for PKD, carbamazepine was later found to be as useful and was introduced as a treatment by . This drug currently appears to be the one that is most commonly used for this disorder.

After the 1963 paper by Lance, reported the next big family with the same type of PXD as Mount and Reback’s case and thought that Lance’s family (1963) represented a variant because there were only tonic spasms and no movements in that family. Richards and Barnett emphasized the nonkinesigenic nature of the attacks and thought that the terms rigidity, tremor, dystonia, torsions, spasm, athetosis, chorea, and hemiballism could all be used for such movements, often blending into each other. To emphasize the postural and increased tone, they added “dystonic” to the label. They recommended avoiding the term “epilepsy” until the pathophysiology is better known. Richards and Barnett coined the term “paroxysmal dystonic choreoathetosis” (PDC), which was later adopted by Lance in 1977. The terms “paroxysmal non-kinesigenic choreoathetosis” and “paroxysmal dystonia” are sometimes used instead of PDC ( ). We have adopted the term “paroxysmal nonkinesigenic dyskinesia” (PNKD) proposed by .

The original cases that were reported as PNKD were idiopathic and usually familial. It was not long before symptomatic cases began to be reported in which the attacks of movements were reported as a PNKD: perinatal encephalopathy ( ), encephalitis ( ), and head injury ( ; ). However, earlier reports of symptomatic PNKD had been described as a manifestation of multiple sclerosis, but considered as a form of epilepsy ( ; ; ). Many other causes have been reported since the cases in the 1950s and 1960s (see later).

One of the most enlightening papers ( ) achieved the following:

• 1.

  It discovered Forssman’s paper (1961).

• 2.

  It placed together as one syndrome the families that , , , and had reported, bringing them all in under the term “familial paroxysmal dystonic choreoathetosis” (PDC), which has a duration of attacks from 5 minutes to 4 hours.

• 3.

  It expanded the description of Lance’s own previously reported family (1963), which he now classified as having this disorder instead of the seizure disorder that he had originally considered.

• 4.

  It added another family with PXD that had attacks induced by continuous exercise rather than sudden movement that affected the legs with a duration between 5 and 30 minutes. (These were the first cases of what is now recognized as paroxysmal exertional dyskinesia.)

• 5.

  It classified the PXDs into three groups separated primarily by duration of action (prolonged, intermediate, and brief attacks) and secondarily by precipitating factors.

• 6.

  It reported the therapeutic response to clonazepam in some patients with the prolonged attacks.

• 7.

  It mentioned normal autopsy findings in two individuals with the prolonged attacks.

• 8.

  It summarized the literature to that date.

• 9.

  It pointed out that the Forssman and Lance families with the prolonged attacks had dystonic postures without choreoathetosis, whereas the Mount and Reback and the Richards and Barnett families had choreoathetosis.

• 10.

  It explained that over time, patients with sustained spasms can eventually develop writhing movements, thereby linking these phenotypes together.

• 11.

  It commented that in all types of PXDs, males are more affected than females.

Instead of Lance’s proposed classification (item 5 in the preceding list) based on duration of the attacks, the classification scheme that is adopted here is the one based on precipitating factors suggested by .

The next historical advances were the recognition that (1) idiopathic PNKD can occur sporadically and not just in families ( ) and (2) sporadic PNKD is often psychogenic in origin ( ; ).

Paroxysmal hypnogenic dyskinesia

described two families in which several members had attacks of involuntary movement that occurred during sleep. These appear to be the first cases of PHD to be reported. Family W is of particular interest because some affected members had classic PKD, some had hypnogenic, and others had a combination. Case 3 in this family began with the hypnogenic variety at age 8. By age 11, daytime attacks also occurred, sometimes triggered by sudden movement. Gradually, the hypnogenic episodes disappeared, leaving the patient with kinesigenic dyskinesia that responded to anticonvulsants. Lugaresi and colleagues ( ; ) independently rediscovered and eventually popularized the syndrome of PHD.

In addition to these short-duration attacks, Lugaresi and colleagues (1986) reported long-duration hypnogenic attacks. Such long-duration attacks occur in a minority of individuals with PHD. These longer attacks last from 2 to 50 minutes and do not respond to medication, including anticonvulsants, tricyclics, benzodiazepines, and antipsychotics.

There has long been considerable speculation as to whether the short-duration hypnogenic attacks could be a manifestation of epilepsy, because they respond so well to anticonvulsants. The lack of abnormal electroencephalogram (EEG) findings during the attack has been used to argue against this concept. However, there is accumulating evidence that many PHDs are indeed the result of seizures. Tinuper and colleagues (1990) described three patients with this disorder who had EEG evidence for frontal lobe seizures as a cause of the attacks. Sellal and colleagues (1991) and Meierkord and colleagues (1992) studied a series of patients with hypnogenic dystonia and concluded that these represent seizure disorders, particularly of frontal lobe epilepsy because repeated nocturnal EEG recordings often reveal epileptic patterns of abnormalities. Seizures arising near the mesial posterior frontal supplementary sensorimotor area may be a particular culprit in inducing PHDs in children ( ). These types of seizures tend to be brief and frequent, with bilateral tonic posturing, gross proximal limb movements, and preserved consciousness. Dystonic and other dyskinetic features may result from spread of epileptic activity from the mesial frontal region to the basal ganglia because there are close anatomic connections between them. It appears that the short-lasting attacks of PHDs are most likely the result of seizures, but the question remains whether patients without abnormal EEGs and more prolonged hypnogenic attacks could have something more akin to the PXDs. In a family with autosomal dominant nocturnal frontal lobe epilepsy, interictal EEGs were normal, but ictal video EEG studies showed that the attacks were partial seizures with frontal lobe origin ( ). reviewed epilepsy masquerading as a movement disorder, and they concluded that most cases of hypnogenic dyskinesias are considered to be due to epilepsy, as did , with cyclic alternating EEG pattern thought to be a provocative factor ( ).

The genetics of hypnogenic dyskinesias/seizures has been explored. A large autosomal dominant Australian family ( ) and a Norwegian family ( ) have been described with mutations in the nicotinic acetylcholine receptor alpha4 subunit (CHRNA4) gene, located on chromosome 20q13.2–q13.3. A second acetylcholine receptor subunit, CHRNB2, is also associated with autosomal dominant nocturnal frontal lobe epilepsy ( ). Another family with autosomal dominant hypnogenic frontal lobe epilepsy has been mapped to 15q24 ( ).

In addition to epilepsy mimicking hypnogenic PXDs, there is a syndrome of infantile convulsions and PXDs, referred to as the infantile convulsions with choreoathetosis (ICCA) syndrome ( ). The gene for this disorder has been mapped to the pericentromeric region of chromosome 16 (see the discussion in the section on PKD and also in the section on molecular genetics of paroxysmal dyskinesias). Single-photon emission computed tomography (SPECT) studies revealed alterations in local cerebral perfusion in the sensorimotor cortex, the supplementary motor areas, and the pallidum ( ).

Transient paroxysmal dyskinesias in infancy

introduced a new type of PXD that he called “paroxysmal torticollis in infancy.” He described 12 cases of intermittent head tilting in young infants. The age at onset was between 2 and 8 months of age, except for three cases, in which the first attacks occurred at 14, 17, and 30 months. The attacks would occur about two or three times a month and last from 10 minutes to 14 days, usually 2 to 3 days. The head would tilt to either side and often rotate slightly to the opposite side. There is no distress unless a parent attempts to straighten the head, upon which the baby cries. In some cases, the head tilting is associated with vomiting, pallor, and agitation for a short period. The infant is normal between attacks, which disappear after months or years, usually around age 2 or 3 years. Subsequently, several similar cases have been described ( ; ; ), including familial cases ( ). reported a patient whose father had a similar condition in early infancy, suggesting that this disorder is hereditary.

The clinical picture of paroxysmal torticollis in infancy ( Video 24.1 ) that has evolved is that the trunk also can be involved, with lateral curvature concave to the same side as the head tilting, and the ipsilateral leg can be flexed. Onset can be as early as the first months of life and can recur every couple of weeks until they disappear before the age of 2 years. Each attack can last a couple of hours to a couple of weeks. In between attacks, the child is normal. The main differential diagnosis is a posterior fossa tumor and Sandifer syndrome (in which head tilt is due to gastroesophageal reflux) ( ).

Video 22.1 Paroxysmal torticollis in infancy.

In 1988, the clinical spectrum expanded with the report by Angelini and colleagues (1988) under the name “transient paroxysmal dystonia in infancy.” They described nine patients who had onset of the PXDs between 3 and 5 months of age, except for one patient who had an onset at age 1 month. Three had a history of perinatal brain damage, and six did not. The attacks consisted of opisthotonus, increased muscle tone with twisting of the limbs, and, in three, neck and trunk twisting, thereby linking this with paroxysmal torticollis in infancy. The attacks last several minutes, with a maximum of 2 hours in one patient. They would occur from several times per day ( Video 24.2 ) to once a month. Remission occurred between the ages of 8 and 22 months, with two not yet having reached a remission.

Video 22.2 Paroxysmal dystonia in infancy.

described an infant with head turning and posturing of the right arm lasting from 45 minutes to 18 hours. There were six attacks from age 26 months to age 40 months. The author did not mention the possible diagnosis of paroxysmal torticollis in infancy and made a diagnosis of PDC instead. One should consider the possibility that PNKD may occur in infancy and disappear over several months. If so, then the paroxysmal torticollis in infancy of Snyder and the paroxysmal dystonia in infancy of Angelini may represent the lowest age spectrum of PNKD and a benign form of the disorder.

Some patients with benign paroxysmal torticollis of infancy come from kindreds with familial hemiplegic migraine linked to CACNA1A mutation, and after recovering from these episodes as they reach childhood, they might have migraines ( ). In fact, a family with individual members of the kindred having one or more of paroxysmal tonic upgaze, benign paroxysmal torticollis of infancy, and EA with familial migraine and a CACNA1A mutation (as in EA-2) has been reported ( ). The clinical picture of benign paroxysmal torticollis of infancy has been summarized to consist of attacks usually lasting less than a week, recurring from every few days to every few months, improving by age 2 years, and ending by age 3; there is very frequently a family history of migraine ( ).

Intrauterine cocaine exposure can be associated with multiple transient dyskinesias. described four infants who tested positive for cocaine metabolite at birth with subsequent transient dystonic reactions, beginning at 3 hours to 3 months of age and persisting for several months.

The clinical syndrome of transient PXD of infancy appears distinct from the syndrome referred to as “benign paroxysmal tonic upgaze of childhood” ( ; ; ; ), which is a sustained tonic conjugate upward deviation of the eyes that begins in infancy and eventually disappears in childhood. This appears to be an autosomal dominant disorder ( ). An infant with tonic upgaze was found to have a partial tetrasomy of 15q ( ). Ataxia may be present, and there can be clumsiness and delayed walking. The ocular deviations lessen in the morning hours and disappear with sleep. Acetazolamide is not effective; however, Campistol and colleagues (1993) reported levodopa to be effective. Perhaps the tonic upgaze with diurnal fluctuations would be a better term than “paroxysmal.” Not all cases of infantile transient tonic upgaze disturbance are benign, although the mean age of offset is 2.5 years ( ). published a review of this disorder. The family reported by Roubertie and colleagues (2008) suggests that tonic upgaze and transient torticollis and EA-2 may be related. A secondary cause of paroxysmal tonic upgaze has been reported. A 1-year-old girl with a hypomyelinating leukoencephalopathy, who presented in the neonatal period with episodes of sustained paroxysmal tonic upward gaze, roving eye movements, pendular nystagmus, and severe hypotonia, with the later appearance of pyramidal and extrapyramidal signs and no development ( ).

Another paroxysmal ocular disorder, known as paroxysmal ocular downward deviation, has been described in normal and brain-damaged infants ( ; ). The ocular displacement was accompanied by closure of the upper eyelids, and the episode lasted seconds.

The syndrome of benign myoclonus of infancy can be mistaken for infantile spasms, but the benign EEG and clinical course allow for a clear distinction. The movements are sudden myoclonic and shuddering episodes of the head and shoulders ( ; ). The jerks often repeat in a series, and consciousness remains intact.

Another benign paroxysmal disorder in infants is spasmus nutans. It consists of a slow (2.4 Hz) tremor of the head, usually horizontal, and often an associated pendular nystagmus ( ). It tends to disappear within 6 months.

Episodic (paroxysmal) ataxias and tremor

Intermittent ataxia can be due to metabolic defects such as Hartnup disease ( ), pyruvate decarboxylase deficiency ( ; , ), and maple syrup urine disease ( ). Fever often triggers the attacks of ataxia. In one case with pyruvate decarboxylase deficiency ( ), choreoathetosis tended to accompany the ataxia. Paroxysmal ataxia and dysarthria also have been reported to occur in multiple sclerosis ( ; ; ; ; ), which, as remarked previously, is a disorder that also can cause paroxysmal choreoathetosis/dystonia. The attacks of paroxysmal ataxia in multiple sclerosis last seconds and are thus much shorter than the attacks described later. They also can respond to carbamazepine. Paroxysmal ataxia also has been reported in Behçet disease ( ).

An important advance was the discovery by Griggs and colleagues (1978) that acetazolamide can effectively prevent attacks. These authors showed this benefit in one kindred with familial paroxysmal ataxia. The following year, had similar results in another kindred. , reported a woman who had paroxysmal tremor, both intention and resting, associated with ataxia and postural instability during the attack; acetazolamide eliminated the attacks. Factor and colleagues (1991) reported an infant who had three attacks of coarse tremor and an orofacial dyskinesia that resembled that seen with tardive dyskinesia. Each attack lasted several hours before spontaneously clearing. Tetrahydrobiopterin, the cofactor for the enzymes tyrosine hydroxylase and phenylalanine hydroxylase, was reduced. The child responded to levodopa.

reported a patient with PNKD in a background of hereditary ataxia. Onset of PNKD was at age 10; onset of ataxia was at age 19. During an attack, which could last from 10 minutes to 4 hours, there was an accompanying increase of ataxia. Initially there was an 8-month response to acetazolamide. After the drug was no longer effective, the patient’s PNKD responded to clonazepam. This patient might be a link between familial PNKD and paroxysmal ataxia.

Several other reports of acetazolamide-responsive familial paroxysmal ataxia have been reported ( ; ; ). Although CT has been normal, magnetic resonance imaging (MRI) studies have revealed selective atrophy in the anterior cerebellar vermis ( ).

Families with a combination of periodic ataxia and persistent, continuous electrical activity in several muscles, reported either as myokymia ( ; ; ; ) or as neuromyotonia ( ), have been described. Description of the attacks, which are brief and are sometimes preceded by sudden movement, include dyskinetic movements and sustained posturing, ataxia, dysarthria, and vertigo. This type of paroxysmal ataxia is now called EA 1 (EA-1).

In 1986, classified the hereditary EAs into three syndromes. In one group are those cases associated with persistent myokymia or neuromyotonia (now called EA-1). They described the attacks being precipitated by fatigue, excitement, stress, and physical trauma, but the family reported by Vaamonde and colleagues (1991) had attacks triggered by sudden movement, and kinesigenicity is now recognized as a feature. There is no dizziness or vertigo. The attacks last 2 minutes or less. Acetazolamide and anticonvulsants are usually ineffective. The gene for this type of paroxysmal ataxia has been located at chromosome 12p13 ( ). Subsequently this mutation was found in the KCNA1 gene and is a potassium channelopathy referred to as EA-1 ( ).

The second group (now known as EA-2) is featured by attacks of ataxia (with or without interictal nystagmus and with or without persistent ataxia), responding to acetazolamide or amphetamines. The attacks are precipitated by exercise, fatigue, or stress and occasionally by carbohydrate or alcohol ingestion. In addition to ataxia, the attacks are accompanied by vertigo, headache, nausea, and malaise. The attacks last for several hours or until the patient falls asleep. Additional families have been reported with these features ( ; ; ). The siblings reported by Bain and colleagues (1991) had persistent diplopia secondary to superior oblique paresis as part of the syndrome. Using ( ³¹ P) nuclear magnetic resonance spectroscopy, Bain and colleagues (1992) found the pH levels in the cerebellum to be increased in untreated subjects with acetazolamide-responsive paroxysmal ataxia; the pH dropped to normal with treatment. The gene for this type of paroxysmal ataxia has been mapped to chromosome 19p13, with a mutation in the CACNA1A gene related to calcium channels ( ; ; ).

listed a third group, which is kinesigenic. Typical PKD can occur in some members of the family. The attacks of ataxia last minutes to hours, whereas the PKD lasts seconds. The disorder can resolve with time. Acetazolamide appears to be ineffective, but phenytoin is effective for both the kinesigenic ataxia and the PKD. In their review, place this third type with associated PKD in the first group of paroxysmal ataxias. Genotyping has now definitively placed this as EA-1 ( ).

Miscellaneous paroxysmal disorders

reported two patients with posttraumatic periodic, rhythmical movements of the tongue. The attacks occurred about every 20 seconds, and each attack lasted 10 seconds. They consisted of three undulations per second. Eventually, the movements diminished. Other cases of episodic lingual dyskinesias were associated with epilepsy ( ) and pontine ischemia ( ).

A few PXDs are mentioned here but are not discussed further. These are Sandifer syndrome (prolonged head tilting in children after eating, as a result of gastroesophageal reflux) (see the review by ); hyperekplexia (excessive startle syndrome with complex movements) (see the review by and Chapter 18 on myoclonus); stereotypy ( Chapter 16 ) ( ; ), and paroxysmal bursts of myoclonus and tics. Classically, stereotypy, myoclonus, and tics are each recognized as a specific class of movement disorders, and they characteristically manifest as paroxysmal bursts of their type of movement. As a result, their discussion should be separated from discussion of conditions labeled as “paroxysmal.” Shuddering attacks in children ( ) are brief bursts of rapid shivering-like movements of the head and arms, occurring up to 100 times per day; they can begin in infancy or in older children, and they resolve over time. The attacks last several seconds without impairment of consciousness. The frequency of shuddering movements as seen on electromyogram (EMG) or EEG was similar to that of essential tremor ( ).

Paroxysmal kinesigenic dyskinesia

• Duration: Seconds to 5 minutes

• Characteristic trigger factor: Sudden movement

• Precipitant: Startle

• Precipitant: Hyperventilation

• Treatment: Responds well to anticonvulsants

• Cause:

  • Primary—familial, sporadic

  • Secondary

• Genetics ( , , ):

  • PRRT2

  • ADCY5

  • SCN8A

  • SLC16A2

  • EKD2

Note that the effectiveness of anticonvulsants correlates with brief duration of the paroxysms rather than their being triggered by sudden movement. Diagnostic criteria for PKD have been proposed ( ).

A family of paroxysmal kinesigenic atonia has been reported ( ). There was no alteration of consciousness or EEG findings of epilepsy. Anticonvulsants were effective in reducing the attacks. This has not been replicated; thus, it is not clear whether the atonia could have been functional

Paroxysmal nonkinesigenic dyskinesia (Mount-Reback type)

• Duration: 2 minutes to 4 hours

• Characteristic trigger factors: Coffee, alcohol, and other nonkinesiogenic factors

• Treatment: Not sensitive to anticonvulsants

• Cause:

  • Primary—familial, sporadic

  • Secondary

  • Psychogenic

• Genetics ( , ):

  • PKND (MR1)

  • PRRT2

  • ADCY5

  • SLC2A1

  • ATP1A3

  • KCNMA1

  • FGF14

  • GAD-1