cobblestone lissencephaly without muscular or ocular involvement

Cobblestone lissencephaly without muscular or ocular involvement is a disorder primarily affecting brain development, resulting in a spectrum of malformations that predominantly impact neurological function. The condition is caused by pathogenic variants in the LAMB1 gene, which plays an important role in brain structure and neuronal migration. It is inherited in an autosomal recessive manner and is extremely rare, affecting fewer than 1 in a million people. The disorder typically presents in early childhood with severe developmental challenges and neurological abnormalities.

Individuals with cobblestone lissencephaly without muscular or ocular involvement experience significant neurological and developmental challenges. Characteristic features include intellectual disability, motor delay, and seizures, with common findings such as severe developmental delay, hydrocephalus, and an increased head circumference. Additional consistent features are abnormalities of brain structures such as cerebellar vermis and hemisphere hypoplasia, as well as abnormal cerebral white matter morphology. Some individuals may also have less frequently observed features such as hypoplasia of the corpus callosum, occipital encephalocele, hypotonia, optic atrophy, hearing impairment, or cataract. Not all individuals experience every feature, and severity varies considerably.

Cobblestone lissencephaly without muscular or ocular involvement is caused by pathogenic variants in the LAMB1 gene, which encodes the laminin beta 1 protein. This protein is crucial for proper brain development and neuronal migration, and disruptions in its function lead to the characteristic brain malformations seen in affected individuals. The condition is inherited in an autosomal recessive pattern, meaning that an affected individual has received one mutated copy of the gene from each parent. This condition is more common when parents share a common ancestor, which increases the likelihood that both carry the same rare genetic variant. Families are encouraged to seek genetic counseling to discuss inheritance, recurrence risks, and options for carrier testing. Associated genes include LAMB1.