Trait Document

Epilepsy restricted to Females with Mental Retardation (EFMR) is an X-linked genetic condition with features limited entirely to females. This condition is characterized by early-onset epilepsy, varying degrees of intellectual disability, and autistic behaviors. The average age of seizure onset is fourteen months, but ranges widely from four to thirty-six months. Febrile seizures (i.e., seizures that occur due to high fevers) and seizures occurring in clusters are often seen in females with EFMR. The types of seizures seen in EFMR include generalized tonic clonic, myoclonic, and complex partial seizures. Although a common feature, not all females with EFMR have intellectual disability. Autistic features, obsessive and aggressive behaviors are often seen in this condition.

EFMR is caused by a mutation or change in the PCDH19 gene which encodes the protocadherin 19 protein. This protein, along with other protocadherins, help cells adhere to each other and to their surroundings. Mutations in the PCDH19 gene is thought to somehow affect the adhesiveness of the protein. Additionally, the protochadherin 19 protein is known to be primarily expressed in the brain, thus explaining the neurological features seen in EFMR.

Management of EFMR often includes medication for seizure control, as well as developmental evaluations and educational interventions for individuals with developmental delay/intellectual disability and/or autistic behaviors.

EFMR is inherited in an X-linked female-limited expression pattern. This means females that inherit one PCDH19 mutation show signs of EFMR, while males that inherit one PCDH19 mutation typically do not show any signs of EFMR. The mutation can be inherited from an affected mother, unaffected father or it can occur brand new (de novo) in an affected daughter.

The risk to family members depends on whether or not the individual with EFMR has a parent with a PCDH19 mutation. If a father has a PCDH19 mutation, 100% of his daughters will have EFMR. If a mother has a PCDH19 mutation, 50% of her daughters will have EFMR, and 50% of her sons will be unaffected carriers. If neither parent has a PCDH19 mutation, the risk of future pregnancies being affected is very low.

The clinical features of EFMR may resemble another genetic condition called Dravet syndrome, also known as severe myoclonic epilepsy of infancy. Compared to EFMR, Dravet syndrome tends to have earlier onset of seizures, and affects females and males equally. However, since it can be difficult to distinguish these two conditions based solely on clinical features, results from genetic testing are often used to aid in making a diagnosis.