lissencephaly

Lissencephaly is a rare congenital brain malformation characterized by a smooth cerebral cortex caused by defective neuronal migration during early brain development. The name derives from the Greek for smooth brain. On imaging, the cortex appears agyric or pachygyric with reduced gyration and a thick, poorly organized cortex, often with a shallow Sylvian fissure.

Causes and genetics: Lissencephaly results from disruption of neuronal migration between roughly the 12th and 24th weeks of gestation. It has genetic forms caused by mutations in LIS1 (PAFAH1B1), DCX, ARX, RELN, TUBA1A, and others, and can be part of syndromic conditions such as Miller-Dieker syndrome (deletion of 17p13.3).

Classification: Classic lissencephaly (type I) includes agyria or pachygyria. Cobblestone lissencephaly (type II) is a related but distinct malformation in which abnormal neuronal overmigration occurs due to defects in the glial limiting membrane, seen in certain congenital muscular dystrophies.

Clinical features: Infants may present with hypotonia, seizures, and global developmental delay. Vision, feeding, and respiratory issues may be present. Severity ranges from near-normal movement with milder cognitive impact to profound disability and early mortality, especially with associated anomalies.

Diagnosis and management: MRI of the brain is the principal diagnostic test. Genetic testing supports a molecular diagnosis and informs recurrence risk. There is no cure; treatment focuses on seizure control, physical and occupational therapy, feeding support, and management of associated health problems.

Prognosis: Outcomes vary with severity and comorbidities; many affected individuals have significant intellectual and motor impairment.