Periventricular nodular heterotopia in patients with filamin-1 gene mutations: neuroimaging findings.
BACKGROUND
The filamin-1 (FLN-1) gene is responsible for periventricular nodular heterotopia (PNH), which is an X-linked dominant neuronal migration disorder.


OBJECTIVE
To review the clinical and imaging findings in a series of patients with documented filamin-1 mutations.


METHODS
A retrospective review of the medical records and MR studies of a series of patients with PNH and confirmed FLN-1 mutations was done. There were 16 female patients (age range: .67-71 years; mean = 28.6) with filamin-1 gene mutations.


RESULTS
In six of the patients the same mutation was inherited in four generations in one pedigree. In a second pedigree, a distinct mutation was found in two patients in two generations. In a third pedigree, a third mutation was found in four patients in two generations. The remaining four patients had sporadic de novo mutations that were not present in the parents. Ten patients had seizures, and all patients had normal intelligence. In all 16 patients MR demonstrated bilateral near-continuous PNH. There were no consistent radiographic or clinical differences between patients carrying different mutations.


CONCLUSIONS
Patients with confirmed FLN-1 gene mutations are usually female and have a distinctive MR pattern of PNH. Other female patients with this same MR pattern probably harbor FLN-1 mutations and risk transmission to their progeny. This information is important for genetic counseling.
Poussaint
T Y
TY
Department of Radiology, Children's Hospital, Boston, Massachusetts 02115, USA. Tina.Poussaint@TCH.Harvard.edu
Fox
J W
JW
Dobyns
W B
WB
Radtke
R
R
Scheffer
I E
IE
Berkovic
S F
SF
Barnes
P D
PD
Huttenlocher
P R
PR
Walsh
C A
CA
D000293:Adolescent; D000328:Adult; D000368:Aged; D002552:Cerebral Ventricles; D002648:Child; D002675:Child, Preschool; D002828:Choristoma / Q000235:genetics* / Q000473:pathology*; D003285:Contractile Proteins / Q000235:genetics*; D005260:Female; D064448:Filamins; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed
D003285:Contractile Proteins; C578663:FLNA protein, human; D064448:Filamins; D008840:Microfilament Proteins