Clinical Guidance

ATP1A2

• A severe phenotype with seizures, coma, and elevated temperature has been reported with the pathogenic variant in ATP1A2 .

• A severe phenotype with seizures and intellectual disability has been reported with the pathogenic variants and .

CACNA1A. Although further correlation is needed, some suggestive genotype-phenotype correlations exist based on limited data regarding CACNA1A pathogenic variants commonly presenting with nystagmus and other cerebellar signs .

Source: GeneReviews — "Familial Hemiplegic Migraine"

Penetrance

Penetrance appears to be high and is estimated at 80% .

Source: GeneReviews — "Familial Hemiplegic Migraine"

Diagnostic Criteria

Consensus clinical diagnostic criteria for familial hemiplegic migraine (FHM) have been published by the (full text).

Suggestive Findings

FHM is a category of migraine with aura. Note: Migraine with aura is a recurring disorder of neurologic symptoms unequivocally localizable to the cerebral cortex or brain stem. The aura usually develops over a period of five to 20 minutes and lasts less than 60 minutes. Headache, nausea, and/or photophobia usually follow neurologic aura symptoms, either immediately or after a symptom-free interval of less than an hour. The headache usually lasts four to 72 hours but may be completely absent (acephalgic migraine).

Diagnostic criteria for HM

Source: GeneReviews — "Familial Hemiplegic Migraine"

Differential Diagnosis

Migraine without aura (OMIM 157300) (common migraine) is an idiopathic, recurring headache disorder manifesting in attacks lasting four to 72 hours. Typical characteristics of the headache are unilateral location, pulsating quality, moderate or severe intensity, aggravation by routine physical activity, and association with nausea, photophobia, and phonophobia. This headache occurs without neurologic aura symptoms and specifically without hemiparesis. Hemiplegia. The differential diagnosis of hemiplegia includes post-ictal weakness following seizure, transient ischemic attack, stroke, and other non-genetic causes of transient hemiparesis. Stroke.

Source: GeneReviews — "Familial Hemiplegic Migraine"

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with familial hemiplegic migraine (FHM) or simplex hemiplegic migraine (i.e., individuals with an FHM-causing pathogenic variant and an apparently negative family history), the evaluations summarized in this (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with Familial Hemiplegic Migraine System/Concern | Evaluation Neurologic | • Quantitative eye movement exam in persons w/nystagmus or complaints of incoordination or imbalance to look for additional clues of cerebellar involvement • EEG neuroimaging studies if seizures are present in order to further characterize seizure disorder • Neuroimaging studies in those w/impaired responsiveness to assess for cerebral edema Assess for movement disorder in those w/PRRT2-FHM Genetic counseling | By genetics professionals1 to obtain a pedigree inform affected persons their families re nature, MOI, implications of FHM in order to facilitate medical personal decision making Family support resources | Assess need for: • Community or such as Parent to Parent; • Social work involvement for parental support; • Home nursing referral. FHM = familial hemiplegic migraine; MOI = mode of inheritance 1. Medical geneticist, certified genetic counselor, certified advanced genetic nurse Treatment of Manifestations Symptomatic support during an episode of hemiplegic migraine is the only therapy available. Table 5. Treatment of Manifestations in Individuals with Familial Hemiplegic Migraine

Source: GeneReviews — "Familial Hemiplegic Migraine"

Clinical Guidance

In general, vasoconstricting agents should be avoided because of the risk of stroke. Cerebral angiography is hazardous as it may precipitate a severe attack .

Source: GeneReviews — "Familial Hemiplegic Migraine"

Therapies Under Investigation

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

Source: GeneReviews — "Familial Hemiplegic Migraine"

Surveillance Guidelines

Table 6.

Recommended Surveillance for Individuals with Familial Hemiplegic Migraine

System/Concern | Evaluation | Frequency

Neurologic

| Eval by neurologist to assess change in attack frequency /or seizures, development of movement disorder, developmental delay, /or learning disability | Annually or more frequently for worsening symptoms

Source: GeneReviews — "Familial Hemiplegic Migraine"