Genetics

KSS is usually sporadic, and is caused by deletion or insertion mutations in the mitochondrial DNA:

The deletions:

• never include the origins of DNA replication
• up to 50% of cases are caused by a specific 5 kb deletion
• each patient has a single mutant form of mtDNA because the mutation occurs early in development
• the proportion of mutant mitochondria increases with time because the smaller genome replicates quicker

The insertions:

• often the origins of DNA replication are duplicated; such mutant mtDNA accumulates because it is replicated twice as often

Rarely, KSS is inherited as an autosomal dominant trait. In these patients there are a wide variety of mtDNA deletions. It is thought that this form of the disease results from a defective nuclear gene which is involved in mtDNA replication.