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Infantile Epilepsy with Mental Retardation (only girls) - PCDH19

Clinical Features

Clinically similar to Dravet-Syndrome, infantile epilepsy with mental retardation in girls can be caused by mutations in the PCDH19 gene located on the X chromosome.
Initial epileptic seizures manifest themselves between the 6th and 36th month of life. They can be triggered by fever and of various forms (generalized, myclonic-tonic, tonic, focal, absence). Interictal EEG may be normal and/or generalized or focally altered. Many patients initially show normal psychomotor development followed by developmental regression at or after age of onset. Some children are developmentally retarded at birth. Aggressive and/or compulsive or autistic behavior is common; however, some affected patients show no signs of developmental disorder. Intellectual development in later years can therefore range from severely impaired to normal.
Family anamnesis may be positive with clinical manifestation affecting almost exclusively female family members; male family members who carry a disease-causing mutation show no clinical signs of the disease. Mutations in the PCDH19 gene have recently been found in approximately 20% of female patients in a collective of SCN1A-negative, sporadic Dravet Syndrome patients (Depienne C. et al., PLOS Genetics 2009).

Genetic Information

The PCDH19 gene is located on the X chromosome (Xq22.1) and codes for the protein protocadherin, which belongs to the family of cadherines. These proteins play a role in calcium-dependent cell-cell adhesion. The pathogenic mechanism is thought to lie in cellular interference: A pathogenic effect only comes about when normal and mutated cells exist next to each other and interact abnormally. Since as a rule only women develop a cellular mosaic of mutated on non-mutated brain cells (due to random X-inactivation), only females manifest the clinical symptoms of the disease.

Diagnostic