Familial Hemiplegic Migraine Panel
Familial hemiplegic migraine (FHM) is characterized by intense migraine headaches with aura1. Onset of disease is in first or second decade of life. Positive family history of FHM is acknowledged if at least one first-degree relative or second-degree relative has identical attacks.
Familial hemiplegic migraine has been associated with pathogenic variants in genes associated with calcium or sodium channels: ATP1A2, CACNA1A, SCN1A 2-11.
Worldwide prevalence is unknown. 1/10,000 cases in Denmark population (combined incidence of familial and sporadic cases)1.
Major clinical symptoms 1, 3, 9:
- Intense headaches with aura accompanied with hemiparesis (weakness of one side of the body).
- Nausea, vomiting and sensitivity to light
- Visual disturbances (blind spots, flashing lights, double vision and zigzag patterns)
- Sensory loss
- Motor weakness is present in some affected patients,.
- FHM attacks may triggered by exercise, emotional stress, strong foods taste or odors, or minor head trauma.
Less common clinical symptoms:
- Cerebellar signs (nystagmus, late-onset mild ataxia) in ~40%-50% of families with FHM1.
- Seizures during severe attacks.
- Intellectual disability.
Presence of the following clinical features 1:
- Fulfills criteria for migraine with aura,
- Aura includes some degree of hemiparesis
- ≥1 first-degree relative (i.e., parent, sib, offspring) has identical attacks.
- Identification of pathogenic variant in one of the following genes: ATP1A2, CACNA1A or SCN1A
There is no cure for familial hemiplegic migraine to date, but several treatments can relieve symptoms1.
- Proper diet
- Avoiding direct light exposure
- Avoiding factors that can trigger attacks (specific food, odors, stress, exercise, head trauma and others)
- Use of migraine prophylactic drugs (tricyclic antidepressants, beta blockers, calcium channel blockers, anti-epileptic medications)
- Migraine without aura (common migraine)
- Inherited disorders with migraines headache (MELAS, MERRF, and other mitochondrial disorders, CADASIL, retinal vasculopathy with cerebral leukodystrophy or RVCL, hereditary hemorrhagic teleangiectasia, familial cerebral cavernous malformations or CCMs)
To confirm/establish the diagnosis, CENTOGENE offers the following tests:
- Familial hemiplegic migraine NGS Panel which includes sequencing of the genes ATP1A2, CACNA1A, SCN1A
- Familial hemiplegic migraine NGS Panel + CNV which includes sequencing and additionally detection of large deletions and duplications from the NGS data
Individuals with a positive family history of familial hemiplegic migraine and relevant symptoms
Confirmation of a clinical diagnosis through genetic testing of familial hemiplegic migraine can allow for genetic counseling and may direct medical management.
Table 1. Overview of genes included in Familial hemiplegic migraine panel
|Gene||OMIM (Gene)||Associated diseases (OMIM)||Inheritance||CentoMD® exclusive variant numbers (++)|
|ATP1A2||182340||familial hemiplegic migraine type 2||AD||27|
|CACNA1A||601011||episodic ataxia type 2; familial hemiplegic migraine 1; spinocerebellar ataxia 6; early infantile epileptic encephalopathy, 42||AD||170|
|SCN1A||182389||generalized epilepsy with febrile seizures plus 2; early infantile epileptic encephalopathy 6; familial hemiplegic migraine-3||AD||132|