The role of PCDH19 in refractory status epilepticus

Epilepsy Behav. 2019 Dec;101(Pt B):106539. doi: 10.1016/j.yebeh.2019.106539. Epub 2019 Oct 31.


PCDH19-Girls Clustering Epilepsy (GCE) is an epileptic syndrome with infantile onset, characterized by clustered and fever-induced seizures, often associated with intellectual disability (ID) and autistic features. Seizures clusters could progress into status epilepticus (SE) with different semiology, both convulsive and nonconvulsive SE (NCSE), and often refractory to conventional antiepileptic drugs. We reviewed literature on PCDH19-GCE, in order to define prevalence, semiology, treatments, and outcome of SE. We conducted a comprehensive review of the PCDH19-GCE literature on the public databases PubMed and EMBASE from January 2008 to July 2019. An overall number of 59 full-text articles were selected, retrieved, and assessed for eligibility. We collected 269 cases with PCDH19-GCE, in 85 of them, a history of SE was reported. Prevalence of SE in all selected series of PCDH19-GCE series is 31.5%. Data on SE were fully exhaustive in 21 cases. There was no gender difference in SE occurrence. Median age at first SE occurrence was 12 months (6 months-11 years). Semiology of SE was reported in 17 cases: it was convulsive in 15 and nonconvulsive in 2. Status epilepticus was refractory in 15 out of 21 cases (71.4%). Benzodiazepine was the most commonly used drug for SE. Alternative treatments with steroids and ketogenic diet were reported as well. We found a high prevalence of ID and autism (19 out of 21 patients, 90%). Despite the relatively high frequency of SE in those patients, there are few specific descriptions of the semiology, EEG pattern, and treatment approach. We strongly believe that a multicenter study looking specifically at SE characteristics might improve the knowledge and consequently the overall outcome. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".

Keywords: Developmental and epileptic encephalopathy; Genetic epilepsy; PCDH19; Prevalence; Status epilepticus.

Publication types

  • Review

MeSH terms

  • Anticonvulsants / therapeutic use
  • Benzodiazepines / therapeutic use
  • Cadherins / genetics*
  • Child
  • Child, Preschool
  • Drug Resistant Epilepsy / complications
  • Drug Resistant Epilepsy / drug therapy
  • Drug Resistant Epilepsy / genetics*
  • Female
  • Humans
  • Infant
  • Intellectual Disability / complications
  • Intellectual Disability / genetics
  • Male
  • Prevalence
  • Protocadherins
  • Status Epilepticus / complications
  • Status Epilepticus / drug therapy
  • Status Epilepticus / epidemiology
  • Status Epilepticus / genetics*


  • Anticonvulsants
  • Cadherins
  • PCDH19 protein, human
  • Protocadherins
  • Benzodiazepines