Peritrigonal and temporo-occipital heterotopia with corpus callosum and cerebellar dysgenesis.
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.
Pediatric Neurology and Neurogenetics Unit, Children’s Hospital A. Meyer-University of Florence, Florence, Italy.
Tiziana
T
Pisano
A James
AJ
Barkovich
Richard J
RJ
Leventer
Waney
W
Squier
Ingrid E
IE
Scheffer
Elena
E
Parrini
Susan
S
Blaser
Carla
C
Marini
Stephen
S
Robertson
Gaetano
G
Tortorella
Felix
F
Rosenow
Pierre
P
Thomas
George
G
McGillivray
Eva
E
Andermann
Frederick
F
Andermann
Samuel F
SF
Berkovic
William B
WB
Dobyns
Renzo
R
Guerrini
D000293:Adolescent; D000328:Adult; D061085:Agenesis of Corpus Callosum / Q000175:diagnosis*; D001921:Brain / Q000002:abnormalities* / Q000473:pathology / Q000503:physiopathology; D002531:Cerebellum / Q000002:abnormalities*; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D054091:Periventricular Nodular Heterotopia / Q000175:diagnosis*