Neuropediatrics 2012; 43 - PS19_04
DOI: 10.1055/s-0032-1307151

Mutations in PCDH19 and Epilepsy: Presentation of a Spanish family with phenotypic heterogeneity

M Linder-Lucht 1, G Aznar Lain 1, R Vivanco Hidalgo 2, A Massot Taurus 2, J Herraiz Rocamora 2, V Poehler 3, B Neubauer 3, R Rocamora Zuñiga 2
  • 1Hospital del Mar, Servicio de Pediatria, Barcelona, Spain
  • 2Hospital del Mar, Unidad de Epilepsia, Barcelona, Spain
  • 3Neuropädiatrie Universitätsklinikum Gießen, Gießen, Germany

Aims: EFMR has been first described in 1971. In 2008, mutations of PCDH19 were identified as causative for EFMR. The disorder shows an unusual, x-linked mode of inheritance whereby females are affected, while transmitting males are spared. The cellular interference model serves to explain this reverse pattern of x-linked inheritance, assuming that the co-existence of two different cell populations interferes with cell-cell-interaction. Recent publications have shown that a wide spectrum of phenotypes is associated with PCDH19 mutations.

Methods: 3 year old girl with unremarkable pregnancy and neonatal course and normal early development who presented at 14, 15 and 18 months with clusters of tonic-clonic seizures and hemiconvulsive seizures in the context of fever. At 31 months, she presented atypical absences. Since then, seizure free with VPA and LEV. Developmentally, she shows a moderate global delay and hyperactivity. Her father has a history of febrile seizures and is diagnosed with myoclonic epilepsy, currently treated with LEV. An aunt of the father suffered from complex febrile seizures up to the age of 12 years and from psychiatric problems. The girl had normal values for routine laboratory data, metabolic screening, karyotype and various asleep and awake EEG. Brain MRI scan showed an arachnoid cyst in the left temporal fossa. SCNA1 mutation could be excluded. We investigated the patient for mutation within PCDH19 gene.

Results: We identified a heterozygous PCDH19 mutation (c.379C>G) in our patient. Her mother showed normal DNA testing, while her father diagnosed with myoclonic epilepsy is homozygous for the mutation, probably demonstrating mosaicism of PCDH19 mutation. His brother is a healthy mutation carrier, his healthy mother and his aunt with complex febrile seizures are heterozygous mutation carriers. His father showed normal DNA testing.

Conclusion: Our case report supports the cellular interference model and demonstrates the phenotypic heterogeneity in PDCH19 mutations.

PCDH19 mutation - epilepsy