Magdalena Budisteanu, Sorina Mihaela Papuc, Catrinel Iliescu, Carmen Burloiu, Oana Tarta-Arsene, Diana Barca, Cristina Motoescu, Carmen Sandu, Alice Dica, Cristina Anghelescu, Adelina Glangher, Dana Craiu, Aurora Arghir

Background: Heterotopia are rare brain malformations with a heterogenous clinical picture ranging from asymptomatic to severe epilepsy and developmental delay/intellectual disability (DD/ID). We report on the results of a study on genetic etiology of heterotopia in a Romanian pediatric population.

Materials and methods: 28 patients with heterotopia were included in this study. Phenotypic evaluation included a general clinical exam completed with neurologic, psychiatric, and psychologic evaluations, brain MRI and electroencephalograms. Genetic investigations included array based comparative genomic hybridization, and classical and next generation sequencing (WES).

Results and discussion: Brain MRI revealed subcortical band heterotopia in 2 patients, periventricular nodular heterotopia in 20 patients, and nodular subcortical heterotopia in 6 cases. Most patients were referred for epilepsy with or without DD/ID. Two genomic imbalances were identified, a duplication of 22q11.2 and a deletion of 7q35 which includes CNTNAP2 gene. A pathogenic frameshift mutation in DCX gene in a girl with band heterotopia; another patient with a complex phenotype has a pathogenic mutation in PIK3CA gene and a compound heterozygous mutation in VPS13D gene. Our study brings new data on the clinical features and epilepsy phenotypes. Both genomic inbalances and gene mutations were detected in our patient group. Brain imaging and genetic studies were instrumental in the diagnostic and patient care algorithm.

Acknowledgments: for technical support with WES to Medical Genetics Center CRH Craiova. Grants: This work was supported by grants of the Romanian National Authority for Scientific Research Innovation, CCCDI-UEFISCDI, Projects number 87/2019 and 88/2019, COFUND-ERANET E-RARE 3-HETER-OMICS-2, within PNCDI III.

Keywords: heterotopia, epilepsy, neurodevelopment, genetic anomalies

Magdalena Budisteanu
Obregia Clinical Hospital of Psychiatry
Romania

Sorina Mihaela Papuc
"Victor Babes" National Institute of Pathology
Romania

Catrinel Iliescu
Obregia Clinical Hospital of Psychiatry
Romania

Carmen Burloiu
Obregia Clinical Hospital of Psychiatry
Romania

Oana Tarta-Arsene
Obregia Clinical Hospital of Psychiatry
Romania

Diana Barca
Obregia Clinical Hospital of Psychiatry
Romania

Cristina Motoescu
Obregia Clinical Hospital of Psychiatry
Romania

Carmen Sandu
Obregia Clinical Hospital of Psychiatry
Romania

Alice Dica
Obregia Clinical Hospital of Psychiatry
Romania

Cristina Anghelescu
Obregia Clinical Hospital of Psychiatry
Romania

Adelina Glangher
Obregia Clinical Hospital of Psychiatry
Romania

Dana Craiu
Obregia Clinical Hospital of Psychiatry
Romania

Aurora Arghir
"Victor Babes" National Institute of Pathology
Romania