Clinical Characteristics

Features of PCDH19 Clustering Epilepsy (CE)
Not all individuals with a pathogenic variant in the PCDH19 gene have clinical features. How much a pathogenic variant results in symptoms (e.g. seizures, learning difficulties) in an individual varies, even amongst affected individuals in the same family. The main clinical features of this disorder are seizures, abnormal development, and behavioural problems.

The most common age of seizure onset is 8 months, but children can develop seizures anytime between 1.5 and 70 months of age. The first seizures often occur in the setting of a fever. Most seizures occur in clusters and girls can have many seizures in a day for several days. The types of seizures are most commonly focal seizures, but tonic-clonic convulsive seizures can also occur. During a seizure, girls appear fearful and may scream. They are not aware of what is going on around them. They may have stiffening or jerking of one limb, which can sometimes spread to involve the entire body. Most seizures are short, lasting less than a few minutes, but sometimes there are so many of them in a cluster that the child does not recover between seizures. Anti-epileptic drugs (AEDs) are used to stop the seizures and prevent further clusters. In some individuals, the AEDs do not work well and it is difficult to prevent seizures occurring. Fortunately, the epilepsy often improves over time, with seizures becoming less severe and less frequent during adolescence. Some individuals become seizure-free around this time.

Most, but not all, girls have normal development prior to the onset of seizures. Approximately 40% of females with CE have normal intelligence throughout their lives. For the remaining 60% of girls, development slows during childhood and they ultimately develop intellectual disability, which can vary in severity from mild (i.e., will likely be able to attend mainstream education) to severe (will need assistance in all areas of life). It is important to treat the clusters of seizures, as frequent and severe seizures can cause slowing of development. Many affected females have specific problems with planning and organisation, abstract reasoning, and the ability to control their behaviours (‘executive function’ skills).

Mental health and behavioural outcomes
Many children develop autistic features, as well as hyperactivity, attention-deficit disorder, and/or other behavioural disturbances. In adult life, some woman have psychiatric disorders, such as depression and psychosis.