SNP Shot: Genomic Insights

Fumarase deficiency is a disorder primarily impacting the nervous system, particularly the brain. Infants with this condition often present with microcephaly (an unusually small head), atypical brain development, significant developmental delays, reduced muscle tone (hypotonia), and failure to thrive (poor weight gain and growth). Seizures may also occur. Some individuals with fumarase deficiency exhibit distinctive facial characteristics, such as a prominent forehead (frontal bossing), low-positioned ears, a small jaw (micrognathia), widely spaced eyes (ocular hypertelorism), and a flattened nasal bridge. Hepatomegaly (enlarged liver) and splenomegaly (enlarged spleen) can also be associated with the condition, as well as polycythemia (an elevated red blood cell count) or leukopenia (a decreased white blood cell count) in infancy. While most affected individuals survive only a few months, some have lived into their early twenties.

Inheritance:

Fumarase deficiency follows an autosomal recessive inheritance pattern. This means that both copies of the relevant gene in each cell must have a mutation for the disorder to manifest. The parents of an individual with fumarase deficiency each carry a single copy of the mutated gene. Although they typically do not exhibit the symptoms of fumarase deficiency itself, individuals with one mutated copy of the FH gene, including parents of affected children, are prone to developing benign tumors composed of smooth muscle tissue (leiomyomas) in the skin and, in females, the uterus. Additionally, they have a higher risk of developing kidney cancer. This related condition is known as hereditary leiomyomatosis and renal cell cancer (HLRCC).