Phenotypic and imaging features of FLNA-negative patients with bilateral periventricular nodular heterotopia and epilepsy

Zianka Fallil, Heath Pardoe, Robert Bachman, Benjamin Cunningham, Isha Parulkar, Catherine Shain, Annapurna Poduri, Robert Knowlton, Ruben Kuzniecky, Bassel Abou-Khalil, Brian Alldredge, Eva Andermann, Jocelyn Bautista, Sam Berkovic, Alex Boro, Gregory Cascino, Damian Consalvo, Patricia Crumrine, Orrin Devinsky, Dennis DlugosMichael Epstein, Miguel Fiol, Nathan Fountain, Jacqueline French, Daniel Friedman, Eric Geller, Tracy Glauser, Simon Glynn, Sheryl Haut, Jean Hayward, Sandra Helmers, Andres Kanner, Heidi Kirsch, Eric Kossoff, Rachel Kuperman, Daniel Lowenstein, Shannon McGuire, Paul Motika, Edward Novotny, Ruth Ottman, Juliann Paolicchi, Jack Parent, Kristen Park, Neil Risch, Lynette Sadleir, Ingrid Scheffer, Renee Shellhaas, Elliot Sherr, Jerry Shih, Shlomo Shinnar, Rani Singh, Joseph Sirven, Michael Smith, Joe Sullivan, Liu Lin Thio, Anu Venkatasubramanian, Eileen Vining, Gretchen Von Allmen, Judith Weisenberg, Peter Widdess-Walsh, Melodie R. Winawer, Emily Acton, Samantha Hagopian, Sarah Sanchez

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Purpose: Periventricular nodular heterotopia (PVNH) is a malformation of cortical development due to impaired neuronal migration resulting in the formation of nodular masses of neurons and glial cells in close proximity to the ventricular walls. We report the clinical characteristics of the largest case series of FLNA-negative patients with seizures and bilateral periventricular heterotopia. Methods: Participants were recruited through the Epilepsy Phenome/Genome Project (EPGP), a multicenter collaborative effort to collect detailed phenotypic data and DNA on a large number of individuals with epilepsy, including a cohort with symptomatic epilepsy related to PVNH. Included subjects had epilepsy, and MRI confirmed bilateral PVNH. Magnetic resonance imaging studies were visually and quantitatively reviewed to investigate the topographic extent of PVNH, symmetry, and laterality. Key findings: We analyzed data on 71 patients with bilateral PVNH. The incidence of febrile seizures was 16.6%. There was at least one other family member with epilepsy in 36.9% of this population. Developmental delay was present in 21.8%. Focal onset seizures were the most common type of seizure presentation (79.3%). High heterotopia burden was strongly associated with female gender and trigonal nodular localization. There was no evidence for differences in brain volume between PVNH subjects and controls. No relationship was observed between heterotopic volume and gender, developmental delay, location of PVNH, ventricular or cerebellar abnormalities, laterality of seizure onset, age at seizure onset, and duration of epilepsy. Significance: A direct correlation was observed between high heterotopia burden, female gender, and trigonal location in this large cohort of FLNA-negative bilateral PVNH patients with epilepsy. Quantitative MRI measurements indicated that this correlation is based on the diffuse nature of the heterotopic nodules rather than on the total volume of abnormal heterotopic tissue.

Original languageEnglish (US)
Pages (from-to)321-327
Number of pages7
JournalEpilepsy and Behavior
StatePublished - Oct 1 2015

Bibliographical note

Funding Information:
This study was supported by NINDS U01 NS 053998 , as well as planning grants from the Finding a Cure for Epilepsy and Seizures ( FACES ) Foundation, the Andrew's Foundation and the Richard Thalheimer Philanthropic Fund . A.P. was supported by the NINDS ( K23 NS069784 ).

Publisher Copyright:
© 2015 Elsevier Inc.


  • Epilepsy
  • Epilepsy Phenome/Genome Project
  • Periventricular nodular heterotopia


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