LAMC3gene is located on chromosome 9 and encodes the γ3 chain of the extracellular laminin family proteins, associated with cell differentiation, migration, and adhesion, and it is involved in the organization of the cerebral cortex and its gyration. Homozygous or compound heterozygous variants in LAMC3have been described to cause occipital cortical malformations.
Most reported pathogenic variants are biallelic loss-of-function variants, including nonsense, frameshift, and splice-site variants, although missense variants in compound heterozygosity have also been described. The presumed pathogenic mechanism is loss of LAMC3function affecting extracellular matrix-related processes during cortical development, particularly late neuronal migration, cortical organization, and gyrification.
Diagnosis is based on the combination of neuroimaging findings and molecular genetic testing, usually through epilepsy, neurodevelopmental disorder, or brain malformation gene panels, exome sequencing, or genome sequencing. Variant interpretation should consider segregation analysis, zygosity, predicted effect on protein function, population frequency, and consistency with the patient’s neuroradiological and clinical phenotype.
LAMC3