The phenotypic spectrum of PCDH12 associated disorders – Five new cases and review of the literature.

October 30, 2021

Fazeli W1, Bamborschke D S2, Moawia A2, Bakhtiari S3, Tafakhori A4, Giersdorf M5, Hahn A6, Weik A7, Kolzter K8, Shafiee S9, Jin SC10, Körber F11, Lee-Kirsch MA12, Darvish H13, Cirak S2, Kruer MC3, Koy A5


PCDH12 is a member of the non-clustered protocadherin family of calcium-dependent cell adhesion proteins, which are involved in the regulation of brain development and endothelial adhesion. To date, only 15 families have been reported with PCDH12 associated disease. The main features previously associated with PCDH12 deficiency are developmental delay, movement disorder, epilepsy, microcephaly, visual impairment, midbrain malformations, and intracranial calcifications. Here, we report novel clinical features such as onset of epilepsy after infancy, episodes of transient developmental regression, and dysplasia of the medulla oblongata associated with three different novel truncating PCDH12 mutations in five cases (three children, two adults) from three unrelated families. Interestingly, our data suggests a clinical overlap with interferonopathies, and we show an elevated interferon score in two pediatric patients. This case series expands the genetic and phenotypic spectrum of PCDH12 associated diseases and highlights the broad clinical variability.

Keywords: Brain malformation; Epilepsy; Interferonopathy; Intracranial calcification; Movement disorder; PCDH12.