Periventricular heterotopia associated with chromosome 5p anomalies

Area of Science:

• Neurogenetics
• Developmental Neuroscience
• Human Genetics

Background:

• Periventricular heterotopia (PH) is a neuronal migration disorder characterized by nodules of gray matter along the lateral ventricles.
• Mutations in the FLNA gene on the X chromosome are a known cause of PH and related cortical malformations.
• Understanding the genetic basis of PH is crucial for diagnosis and potential therapeutic strategies.

Observation:

• Two subjects presented with bilateral nodular periventricular heterotopia and complex partial seizures.
• Neuroimaging (MRI) revealed heterotopic gray matter and focal gliosis in the periventricular regions.
• Genetic analysis using Fluorescence In Situ Hybridization (FISH) identified distinct chromosomal abnormalities on chromosome 5p.

Findings:

• One subject had a duplication at 5p15.1 [46,XX,dup(5)(p15.1p15.1)].
• The second subject exhibited trisomy of 5p15.33 [46,XY,der(14)t(5;14)(p15.33;p11.2) mat].
• These chromosomal alterations suggest a novel locus for periventricular heterotopia on the telomeric region of chromosome 5p.

Implications:

• The findings expand the known genetic causes of periventricular heterotopia beyond FLNA mutations.
• This study implicates chromosome 5p, specifically the 5p15 region, in the etiology of PH.
• Identification of this new PH locus may aid in diagnosing patients with unexplained heterotopia and seizures.