OBJECTIVE: To describe a homogeneous subtype of periventricular nodular heterotopia (PNH) as part of a newly defined malformation complex. METHODS: Observational study including review of brain MRI and clinical findings of a cohort of 50 patients with PNH in the temporo-occipital horns and trigones, mutation analysis of the FLNA gene, and anatomopathologic study of a fetal brain. RESULTS: There were 28 females and 22 males. All were sporadic with the exception of an affected mother and son. Epilepsy occurred in 62%, cerebellar signs in 56%, cognitive impairment in 56%, and autism in 12%. Seventy percent were referred within the 3rd year of life. Imaging revealed a normal cerebral cortex in 76% and abnormal cortical folding in 24%. In all patients the hippocampi were under-rotated and in 10% they merged with the heterotopia. Cerebellar dysgenesis was observed in 84% and a hypoplastic corpus callosum in 60%. There was no gender bias or uneven gender distribution of clinical and anatomic severity. No mutations of FLNA occurred in 33 individuals examined. Heterotopia in the fetal brain revealed cytoarchitectonic characteristics similar to those associated with FLNA mutations; cortical pathology was not typical of polymicrogyria. Cerebellar involvement was more severe and the hippocampi appeared simple and under-rotated. CONCLUSIONS: This series delineates a malformation complex in which PNH in the trigones and occipito-temporal horns is associated with hippocampal, corpus callosum, and cerebellar dysgenesis. This subtype of PNH is distinct from classic PNH caused by FLNA mutations.
OBJECTIVE: To describe a homogeneous subtype of periventricular nodular heterotopia (PNH) as part of a newly defined malformation complex. METHODS: Observational study including review of brain MRI and clinical findings of a cohort of 50 patients with PNH in the temporo-occipital horns and trigones, mutation analysis of the FLNA gene, and anatomopathologic study of a fetal brain. RESULTS: There were 28 females and 22 males. All were sporadic with the exception of an affected mother and son. Epilepsy occurred in 62%, cerebellar signs in 56%, cognitive impairment in 56%, and autism in 12%. Seventy percent were referred within the 3rd year of life. Imaging revealed a normal cerebral cortex in 76% and abnormal cortical folding in 24%. In all patients the hippocampi were under-rotated and in 10% they merged with the heterotopia. Cerebellar dysgenesis was observed in 84% and a hypoplastic corpus callosum in 60%. There was no gender bias or uneven gender distribution of clinical and anatomic severity. No mutations of FLNA occurred in 33 individuals examined. Heterotopia in the fetal brain revealed cytoarchitectonic characteristics similar to those associated with FLNA mutations; cortical pathology was not typical of polymicrogyria. Cerebellar involvement was more severe and the hippocampi appeared simple and under-rotated. CONCLUSIONS: This series delineates a malformation complex in which PNH in the trigones and occipito-temporal horns is associated with hippocampal, corpus callosum, and cerebellar dysgenesis. This subtype of PNH is distinct from classic PNH caused by FLNA mutations.
Authors: Shihong Li; Zhaohui Jin; Samir Koirala; Lihong Bu; Lei Xu; Richard O Hynes; Christopher A Walsh; Gabriel Corfas; Xianhua Piao Journal: J Neurosci Date: 2008-05-28 Impact factor: 6.167
Authors: Y Z Ekşioğlu; I E Scheffer; P Cardenas; J Knoll; F DiMario; G Ramsby; M Berg; K Kamuro; S F Berkovic; G M Duyk; J Parisi; P R Huttenlocher; C A Walsh Journal: Neuron Date: 1996-01 Impact factor: 17.173
Authors: W B Dobyns; E Andermann; F Andermann; D Czapansky-Beilman; F Dubeau; O Dulac; R Guerrini; B Hirsch; D H Ledbetter; N S Lee; J Motte; J M Pinard; R A Radtke; M E Ross; D Tampieri; C A Walsh; C L Truwit Journal: Neurology Date: 1996-08 Impact factor: 9.910
Authors: V L Sheen; P H Dixon; J W Fox; S E Hong; L Kinton; S M Sisodiya; J S Duncan; F Dubeau; I E Scheffer; S C Schachter; A Wilner; R Henchy; P Crino; K Kamuro; F DiMario; M Berg; R Kuzniecky; A J Cole; E Bromfield; M Biber; D Schomer; J Wheless; K Silver; G H Mochida; S F Berkovic; F Andermann; E Andermann; W B Dobyns; N W Wood; C A Walsh Journal: Hum Mol Genet Date: 2001-08-15 Impact factor: 6.150
Authors: Gretchen Wieck; Richard J Leventer; Waney M Squier; An Jansen; Eva Andermann; Francois Dubeau; Anna Ramazzotti; Renzo Guerrini; William B Dobyns Journal: Brain Date: 2005-12 Impact factor: 13.501
Authors: Kimberly A Aldinger; Andrew E Timms; Zachary Thomson; Ghayda M Mirzaa; James T Bennett; Alexander B Rosenberg; Charles M Roco; Matthew Hirano; Fatima Abidi; Parthiv Haldipur; Chi V Cheng; Sarah Collins; Kaylee Park; Jordan Zeiger; Lynne M Overmann; Fowzan S Alkuraya; Leslie G Biesecker; Stephen R Braddock; Sara Cathey; Megan T Cho; Brian H Y Chung; David B Everman; Yuri A Zarate; Julie R Jones; Charles E Schwartz; Amy Goldstein; Robert J Hopkin; Ian D Krantz; Roger L Ladda; Kathleen A Leppig; Barbara C McGillivray; Susan Sell; Katherine Wusik; Joseph G Gleeson; Deborah A Nickerson; Michael J Bamshad; Dianne Gerrelli; Steven N Lisgo; Georg Seelig; Gisele E Ishak; A James Barkovich; Cynthia J Curry; Ian A Glass; Kathleen J Millen; Dan Doherty; William B Dobyns Journal: Am J Hum Genet Date: 2019-08-29 Impact factor: 11.025
Authors: Heath R Pardoe; Simone A Mandelstam; Rebecca Kucharsky Hiess; Ruben I Kuzniecky; Graeme D Jackson Journal: Epilepsy Res Date: 2014-10-30 Impact factor: 3.045
Authors: Erin L Heinzen; Adam C O'Neill; Xiaolin Zhu; Andrew S Allen; Melanie Bahlo; Jamel Chelly; Ming Hui Chen; William B Dobyns; Saskia Freytag; Renzo Guerrini; Richard J Leventer; Annapurna Poduri; Stephen P Robertson; Christopher A Walsh; Mengqi Zhang Journal: PLoS Genet Date: 2018-05-08 Impact factor: 5.917
Authors: Giorgi Kuchukhidze; Florian Koppelstaetter; Iris Unterberger; Judith Dobesberger; Gerald Walser; Julia Höfler; Laura Zamarian; Edda Haberlandt; Kevin Rostasy; Martin Ortler; Thomas Czech; Martha Feucht; Gerhard Bauer; Margarete Delazer; Stephan Felber; Eugen Trinka Journal: Epilepsy Res Date: 2013-06-27 Impact factor: 3.045