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


RESULTS
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.


CONCLUSIONS
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.
NYU Epilepsy Center, Langone Medical Center, New York University, New York, NY, USA.
Zianka
Z
Fallil
NYU Epilepsy Center, Langone Medical Center, New York University, New York, NY, USA.
Heath
H
Pardoe
NYU Epilepsy Center, Langone Medical Center, New York University, New York, NY, USA.
Robert
R
Bachman
NYU Epilepsy Center, Langone Medical Center, New York University, New York, NY, USA.
Benjamin
B
Cunningham
Epilepsy Genetics Program, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, USA.
Isha
I
Parulkar
Epilepsy Genetics Program, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, USA.
Catherine
C
Shain
Epilepsy Genetics Program, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, USA.
Annapurna
A
Poduri
UCSF Epilepsy Center, UCSF, San Francisco, CA, USA.
Robert
R
Knowlton
NYU Epilepsy Center, Langone Medical Center, New York University, New York, NY, USA. Electronic address: ruben.kuzniecky@nyumc.org.
Ruben
R
Kuzniecky
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D002658:Developmental Disabilities / Q000473:pathology; D004827:Epilepsy / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005260:Female; D005334:Fever / Q000453:epidemiology / Q000209:etiology; D064448:Filamins / Q000235:genetics*; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D059906:Neuroimaging; D054091:Periventricular Nodular Heterotopia / Q000150:complications / Q000235:genetics* / Q000473:pathology; D012640:Seizures / Q000453:epidemiology / Q000209:etiology; D012727:Sex Characteristics; D055815:Young Adult
C578663:FLNA protein, human; D064448:Filamins
Epilepsy; Epilepsy Phenome/Genome Project; Periventricular nodular heterotopia