[Phenotypic variability in a family with genetically verified familial hemiplegic migraine type 2]

Area of Science:

• Genetics
• Neurology
• Molecular Biology

Background:

• Familial hemiplegic migraine (FHM) is a rare subtype of migraine with aura, characterized by hemiplegia.
• Mutations in the ATP1A2 gene, encoding the alpha-2 subunit of the sodium-potassium pump, are a known cause of FHM type 2 (FHM2).
• FHM2 typically presents with migraine, but associated neurological symptoms can vary.

Observation:

• A 13-year-old girl experienced a comatose state with hemiparesis and aphasia after physical activity, with a history of childhood epilepsy.
• Her father exhibited similar episodes of prolonged coma, fever, seizures, hemiparesis, and aphasia, alongside a history of childhood epilepsy.
• The paternal grandmother had a history of severe hemiplegic migraine.

Findings:

• Genetic testing revealed a previously identified mutation in the ATP1A2 gene in both the daughter and the father.
• This mutation was linked to the observed neurological symptoms in both affected individuals.
• The findings confirm the genetic basis for FHM2 in this family.

Implications:

• These cases highlight the significant phenotypic variability associated with ATP1A2 mutations in FHM2.
• The study underscores the importance of genetic testing for ATP1A2 mutations in patients with complex neurological presentations, including epilepsy and coma.
• Understanding this variability aids in accurate diagnosis and management of FHM2 and related channelopathies.