PCDH19 defects in girls with infantile myoclonic epilepsy with and without autism

Epilepsy and mental retardation limited to females (EFMR, OMIM 300088) was reported in an extended family in 1971. The mode of inheritance is unique and not completely understood. Recently, defects in the protocadherin 19 gene, PCDH19, were identified in EFMR. This gene is located on the X chromosome and codes for an intercellular adhesion molecule. Subsequently, it became clear that many affected girls suffer from what had been diagnosed a Dravet's Syndrome, without an SCN1A defect. It was shown that PCDH 19 defects are the second leading cause of Dravet's Syndrome in girls. About 20% of SCN1A negative girls are affected. Preliminary diagnostic criteria are:

• Onset of epilepsy between 6 and 36 month of age.

• Generalized tonic-clonic seizures, clonic seizures, myoclonic seizures, absences, unilateral seizures, and partial seizures.

• Developmental regression in about 50% of cases.

• Psychiatric comorbidity (e.g. autism) is possible.

Some of the affected are show various degrees of mental retardation. Long term prognosis is more favourable than in classic Dravet's Syndrome. Seizures may remit or attenuate in higher age, and some women show no significant degree of mental retardation. De novo mutations are a frequent cause of PCDH19 defects. If girls with mental retardation or even autism without seizures may carry PCDH19 mutations needs to be evaluated. We present findings in 120 SCN1A negative girls with suspected Dravet's syndrome.