Autosomal recessive form of periventricular heterotopia.
BACKGROUND
Familial periventricular heterotopia (PH) represents a disorder of neuronal migration resulting in multiple gray matter nodules along the lateral ventricular walls. Prior studies have shown that mutations in the filamin A (FLNA) gene can cause PH through an X-linked dominant inheritance pattern.


OBJECTIVE
To classify cortical malformation syndromes associated with PH.


METHODS
Analyses using microsatellite markers directed toward genomic regions of FLNA and to a highly homologous autosomal gene, FLNB, were performed on two pedigrees to evaluate for linkage with either filamin gene.


RESULTS
Two consanguineous pedigrees with PH that suggest an autosomal recessive inheritance pattern are reported. MRI of the brain revealed periventricular nodules of cerebral gray matter intensity, typical for PH. Seizures or developmental delay appeared to be a common presenting feature. Microsatellite analysis suggested no linkage to FLNA or FLNB.


CONCLUSIONS
Autosomal recessive PH is another syndromic migrational disorder, distinct from X-linked dominant PH. Further classification of these different syndromes will provide an approach for genetic evaluation.
Sheen
V L
VL
Division of Neurogenetics, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, MA 02115, USA.
Topçu
M
M
Berkovic
S
S
Yalnizoglu
D
D
Blatt
I
I
Bodell
A
A
Hill
R S
RS
Ganesh
V S
VS
Cherry
T J
TJ
Shugart
Y Y
YY
Walsh
C A
CA
D000328:Adult; D000368:Aged; D001927:Brain Diseases / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics; D002552:Cerebral Ventricles / Q000002:abnormalities*; D002675:Child, Preschool; D002828:Choristoma / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D041321:Chromosomes, Human, X / Q000235:genetics; D003241:Consanguinity; D003285:Contractile Proteins / Q000235:genetics; D002658:Developmental Disabilities / Q000235:genetics; D004569:Electroencephalography; D005260:Female; D064448:Filamins; D005808:Genes, Recessive; D008040:Genetic Linkage; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics; D018895:Microsatellite Repeats; D008875:Middle Aged; D010375:Pedigree; D012640:Seizures / Q000235:genetics; D014421:Turkey / Q000208:ethnology; D015006:Yemen / Q000208:ethnology
D003285:Contractile Proteins; C578662:FLNB protein, human; D064448:Filamins; D008840:Microfilament Proteins