SNP Shot: Genomic Insights

Isolated congenital asplenia is characterized by the absence of a functional spleen (asplenia) at birth, without other developmental issues. Affected individuals either completely lack a spleen or possess a very small, non-functioning spleen (hyposplenism).

The spleen is a crucial component of the immune system. As part of the lymphatic system, it produces and distributes fluids and immune cells throughout the body. Specifically, the spleen generates phagocytes, immune cells that clear bacteria from the bloodstream to prevent infections. It also stores blood cells that defend against foreign substances and filters out old blood cells. Individuals with isolated congenital asplenia, lacking these splenic immune functions, are highly vulnerable to bacterial infections.

Individuals with isolated congenital asplenia are at risk for severe and recurring infections. These infections commonly manifest as systemic infections (sepsis), inflammation of the membranes surrounding the brain and spinal cord (meningitis), or ear infections (otitis media). The bacterium *Streptococcus pneumoniae* is a frequent cause of these infections.

Without preventive measures and appropriate medical care, the repeated infections associated with isolated congenital asplenia can be fatal.

Inheritance:

Isolated congenital asplenia caused by RPSA gene mutations follows an autosomal dominant inheritance pattern. This means that only one copy of the mutated gene in each cell is enough to cause the disorder. Typically, an affected individual inherits the mutation from a parent who also has the condition. However, some cases arise from new gene mutations during the formation of egg or sperm cells in a parent or during the early stages of embryonic development. These individuals have no family history of the disorder. Notably, some individuals with an RPSA gene mutation linked to isolated congenital asplenia have a normal spleen for reasons that are not yet understood. This is referred to as incomplete penetrance, meaning that not everyone with the gene mutation develops the condition. When the cause of isolated congenital asplenia is unknown, the inheritance pattern is also unclear.