Clinical Guidance

Because of significant inter- and intrafamilial phenotypic variability, reliable genotype-phenotype correlations have been extremely difficult to establish. It is now apparent that phenotypic differences exist not only across families, but also among affected individuals within a family. Indeed, differences in severity and frequency of EA1 attacks have been reported even in monozygotic twins .

Source: GeneReviews — "Episodic Ataxia Type 1"

Penetrance

Most individuals harboring a KCNA1 pathogenic variant exhibit features of EA1; however, penetrance is incomplete.

Source: GeneReviews — "Episodic Ataxia Type 1"

Diagnostic Criteria

No consensus diagnostic criteria for episodic ataxia type 1 (EA1) have been published.

Suggestive Findings

Episodic ataxia type 1 (EA1) should be suspected in individuals with the following clinical, imaging, and laboratory findings.

Clinical manifestations

• Episodic attacks of:

• Generalized ataxia, loss of balance, and jerking movements of the head, arms, and legs

• Dysarthria

• Incoordination of hands

• Weakness

• Tremors

• Muscle twitching/stiffening

• Dizziness

• Stiffening of the body

• Blurred vision, diplopia

• Nausea, headache, and vomiting

• Neuromyotonia (muscle cramps and stiffness)

• Myokymia (muscle twitching with a rippling appearance) occurring in the limbs or especially in the muscles of the face or hands

• Childhood or early-adolescent disease onset (average age of onset: ~8 years)

Source: GeneReviews — "Episodic Ataxia Type 1"

Differential Diagnosis

Episodic ataxia can occur sporadically or in a number of hereditary or acquired disorders.

Table 2.

Disorders to Consider in the Differential Diagnosis of Episodic Ataxia Type 1

Disorder | Gene | MOI | Clinical Features | Onset | Frequency of Attacks | Attack Triggers | Treatment | Interictal Findings

EA21(OMIM 108500) | CACNA1A | AD | • Paroxysmal attacks of ataxia, vertigo, nausea lasting minutes to days; can be assoc w/dysarthria, diplopia, tinnitus, dystonia, hemiplegia, headache (migraine in ~50%)

• Atrophy of cerebellar vermis on MRI

| Typically childhood or early adolescence (range: 2-32 yrs) | Range: 1-2/yr to 3-4/wk | • Stress

• Exertion

• Caffeine

• Alcohol

• Fever

• Heat

• Phenytoin

Source: GeneReviews — "Episodic Ataxia Type 1"

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and therapeutic needs in an individual diagnosed with episodic ataxia type 1, the evaluations summarized (if not already completed) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with Episodic Ataxia Type 1

Source: GeneReviews — "Episodic Ataxia Type 1"

Clinical Guidance

Known triggers of attacks (see , Triggers) should be avoided; physical exertion, emotional stress, and changes in environmental temperature are the most common triggers. Marked generalized myokymia has been reported during induction of anesthesia .

Source: GeneReviews — "Episodic Ataxia Type 1"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Source: GeneReviews — "Episodic Ataxia Type 1"

Surveillance Guidelines

Surveillance should include annual neurologic examination.

Source: GeneReviews — "Episodic Ataxia Type 1"