SNP Shot: Genomic Insights

Lissencephaly with cerebellar hypoplasia (LCH) is a condition impacting brain development. A key feature is lissencephaly, where the brain appears smooth instead of having the typical folds and grooves. Furthermore, the cerebellum, responsible for coordinating movement, is abnormally small (cerebellar hypoplasia). The hippocampus, crucial for learning and memory, and the brainstem, connecting the brain to the spinal cord, are also frequently underdeveloped in individuals with LCH.

People with LCH typically exhibit moderate to severe intellectual disability and developmental delays. Communication abilities are limited or absent, and they experience severe hypotonia (weak muscle tone), ataxia (poor coordination and balance), and challenges in maintaining a seated or standing position without assistance. Recurrent seizures (epilepsy) are common, often starting in early infancy. Visual problems like nearsightedness (myopia) and involuntary eye movements (nystagmus), as well as lymphedema (swelling due to fluid buildup), can also occur.

Inheritance:

LCH caused by mutations in the RELN gene follows an autosomal recessive inheritance pattern. This means that both copies of the RELN gene in an individual must have mutations for the condition to manifest. Parents of an affected child each carry one mutated copy of the gene but usually don't exhibit symptoms themselves. Conversely, when mutations in the TUBA1A gene cause LCH, the condition is inherited in an autosomal dominant manner. In this case, only one copy of the altered TUBA1A gene is enough to cause the disorder. Most TUBA1A-related cases arise from new, spontaneous mutations, meaning the individual is the first in their family to have the condition.