WWOX deficiency is a direct result of autosomal recessive mutations affecting the WWOX gene. Genes are composed of two alleles. One allele comes from the father, and the other comes from the mother. Recessive inheritance means both alleles must be abnormal to cause disease. People with only one defective allele are called heterozygous carriers. Carriers of WWOX mutations are not affected with the condition. However, they can pass the WWOX gene mutation to their children. To have an autosomal recessive disorder such as SCAR12 or WOREE syndrome, two mutated alleles are inherited, one from each parent. SCAR12 and WOREE are also known as monogenic disorders because only one gene is involved.
SCAR12, the less severe of the two syndromes, typically results from a biallelic missense mutation, meaning a missense mutation is inherited from each parent. WOREE on the other hand results from a combination of nonsense mutations, missense mutations and or deletions present on both alleles. The actual combination gives rise to a phenotypic spread which is still not well classified, but varies from severe to extremely severe.