Bilateral polymicrogyria associated with dystonia: A new neurogenetic syndrome?

Area of Science:

• Neuroscience
• Genetics
• Neurology

Background:

• Bilateral perisylvian polymicrogyria (PMG) typically presents with oromotor dysfunction, epilepsy, intellectual disability, and pyramidal signs.
• Extrapyramidal features, such as dystonia, are exceptionally rare in PMG.
• This study investigates a unique cohort of patients presenting with PMG and dystonia.

Purpose of the Study:

• To describe the clinical, genetic, and radiologic features of patients with an unusual association of PMG and dystonia.
• To explore potential underlying mechanisms for dystonia in the context of PMG.
• To determine if this presentation represents a novel neurogenetic disorder.

Main Methods:

• Case series presentation of four unrelated patients.
• Detailed clinical assessments including neurological examinations.
• Neuroimaging (MRI) to characterize the polymicrogyria pattern.
• Whole exome sequencing in two patients to identify potential genetic variants.

Main Results:

• All four patients were female and presented with early-onset dystonia.
• Common PMG features included oromotor dysfunction, speech abnormalities, pyramidal signs, and hypotonia.
• Neuroimaging revealed bilateral PMG with an infolded cortex, predominantly in the perisylvian region.
• Whole exome sequencing did not identify pathogenic variants in known genes for cortical malformations or movement disorders.

Conclusions:

• The co-occurrence of PMG and dystonia is rare and may indicate a distinct clinical entity.
• Impaired connectivity within motor networks or compromised cortical inhibition are potential mechanisms for dystonia in this context.
• This association suggests a possible new neurogenetic disorder requiring further investigation.