Polymicrogyria, Cobblestone Malformations, and Tubulin Mutation (Overmigration beyond Pial Limiting Membrane): Diagnosis, Treatment, and Rehabilitation Approach

Abstract

Polymicrogyria, cobblestone malformations, and tubulinopathies constitute a group of neuronal migration abnormalities beyond the pial limiting membrane. Their etiopathogenesis remains unclear, with proposed environmental and genetic factors, including copy number variations and single-gene disorders, recently categorized.

Polymicrogyria features numerous small circumvolutions separated by large, shallow grooves, often affecting the perisylvian cortex with various presentations. Clinical manifestations vary depending on lesion degree, extent, and location, commonly including epilepsy, encephalopathies, spastic tetraparesis, mental retardation, and cortical function deficits.

Cobblestone malformations exhibit a Roman-like pavement cortex, affecting both hemispheres symmetrically due to disruption of the glia limitans, frequently linked to glycosyltransferase gene mutations. Classified separately from lissencephaly type II, they are associated with congenital muscular dystrophy syndromes such as Fukuyama congenital muscular dystrophy, Walker–Warburg syndrome, and muscle–eye–brain disease.

Tubulinopathies encompass diverse cerebral malformations resulting from α-tubulin isotype gene variants, exhibiting a wide clinical spectrum including motor/cognitive impairment, facial diplegia, strabismus, and epilepsy.

Diagnosis relies on magnetic resonance imaging (MRI) with age-specific protocols, highlighting the gray–white junction as a polymicrogyria marker, though neonatal diagnosis may be challenging due to technical and brain maturity issues.

To date, no effective treatments are available and management include physiotherapy, speech and language therapy, and vision training program for oculomotor disabilities; antiepileptic drugs are commonly necessary, and most severe forms usually require specific nutritional support.

Keywords

polymicrogyria - tubulin - neuronal migration - genetics - rehabilitation

^* These authors have contributed equally to the article.

Publikationsverlauf

Eingereicht: 05. Dezember 2023

Angenommen: 04. April 2024

Artikel online veröffentlicht:
29. Mai 2024

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