SNP Shot: Genomic Insights

Acrocallosal syndrome is a rare congenital disorder identifiable at birth. It involves three key features: agenesis of the corpus callosum (a brain malformation), polydactyly (extra fingers and/or toes), and characteristic facial features. The intensity of these symptoms differs significantly from person to person.

Agenesis of the corpus callosum means the corpus callosum, the structure connecting the brain's two hemispheres, doesn't develop properly during prenatal development. In addition to this, some individuals with acrocallosal syndrome may have other brain abnormalities, such as cysts. These brain structural differences result in developmental delays and intellectual disability, often ranging from moderate to severe. Seizures are also experienced by some.

Polydactyly, the presence of extra fingers or toes, is a common feature of acrocallosal syndrome. These extra digits can be located next to the little finger or toe (postaxial polydactyly) or next to the thumb or big toe (preaxial polydactyly). Syndactyly, where skin is fused or webbed between fingers or toes, may also occur.

The distinctive facial features associated with acrocallosal syndrome can include widely spaced eyes (hypertelorism) and a tall, prominent forehead. An unusually large head size (macrocephaly) is also frequently observed.

Inheritance:

Acrocallosal syndrome caused by mutations in the KIF7 gene follows an autosomal recessive inheritance pattern. This means that an affected individual must inherit a mutated copy of the gene from both parents, who are typically carriers but do not exhibit symptoms themselves. Conversely, acrocallosal syndrome (or severe Greig cephalopolysyndactyly syndrome) due to mutations in the GLI3 gene is considered autosomal dominant. In these cases, only one copy of the altered gene is needed to cause the disorder. These GLI3 mutations are typically new (de novo), arising during the formation of sperm or egg cells, or during early embryonic development, and occur in families with no prior history of the condition.