Three Generations of FLNA-Associated Periventricular Nodular Heterotopia

Area of Science:

• Neurogenetics
• Developmental Neuroscience
• Medical Genetics

Background:

• Periventricular nodular heterotopia (PVNH) is a neuronal migration disorder.
• Mutations in the Filamin A (FLNA) gene are a known cause of PVNH.
• PVNH can present with a range of neurological symptoms.

Observation:

• A family spanning three generations exhibited FLNA gene-associated PVNH.
• A fetus presented with multiple neurological malformations, including absent corpus callosum and PVNH.
• The fetus's mother and grandmother also carried the FLNA mutation; the grandmother had a history of seizures, while the mother was asymptomatic.

Findings:

• Genetic analysis identified a nonsense mutation in the FLNA gene.
• Familial genetic testing and neuroimaging confirmed the FLNA variant and PVNH in multiple family members.
• Phenotypic variability was observed, ranging from asymptomatic carriers to severe fetal malformations.

Implications:

• This case highlights the broad spectrum of PVNH associated with FLNA mutations.
• Genetic counseling is crucial for families with PVNH.
• Understanding FLNA mutations is important for diagnosing and managing fetal central nervous system malformations.