Mutation in Filamin A Causes Periventricular Heterotopia, Developmental Regression, and West Syndrome in Males

Purpose: 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 pattern. Hetero...

Full description

Saved in:
Bibliographic Details
Published in:Epilepsia (Copenhagen) 2006-01, Vol.47 (1), p.211-214
Main Authors: Masruha, Marcelo R., Caboclo, Luis O. S. F., Carrete, Henrique, Cendes, Íscia L., Rodrigues, Murilo G., Garzon, Eliana, Yacubian, Elza M. T., Sakamoto, Américo C., Sheen, Volney, Harney, Megan, Neal, Jason, Sean Hill, R., Bodell, Adria, Walsh, Christopher, Vilanova, Luiz C. P.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Brain Diseases - epidemiology
Brain Diseases - genetics
Brain Diseases - pathology
Cerebral Ventricles - pathology
Choristoma - epidemiology
Choristoma - genetics
Choristoma - pathology
Complex syndromes
Contractile Proteins - genetics
Developmental Disabilities - epidemiology
Developmental Disabilities - genetics
Developmental Disabilities - pathology
DNA Mutational Analysis
Electroencephalography - statistics & numerical data
Familial
Female
Filamins
Genetic Diseases, X-Linked - genetics
Genetic Diseases, X-Linked - pathology
Genotype
Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy
Humans
Infant
Magnetic Resonance Imaging
Male
Malformations of the nervous system
Medical genetics
Medical sciences
Microfilament Proteins - genetics
Mutation - genetics
Mutation, Missense - genetics
Nervous system (semeiology, syndromes)
Neurology
Pedigree
Periventricular heterotopia
Phenotype
Sex Factors
Spasms, Infantile - epidemiology
Spasms, Infantile - genetics
Subependymal heterotopia
Videotape Recording
West syndrome
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Purpose: 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 pattern. Heterozygotic female patients usually remain asymptomatic until the second or third decade of life, when they may have predominantly focal seizures, whereas hemizygotic male fetuses typically die in utero. Recent studies have also reported mutations in FLNA in male patients with PH who are cognitively normal. We describe PH in three male siblings with PH due to FLNA, severe developmental regression, and West syndrome. Methods: The study includes the three affected brothers and their parents. Video‐EEG recordings and magnetic resonance image (MRI) scanning were performed on all individuals. Mutations for FLNA were detected by using polymerase chain reaction (PCR) on genomic DNA followed by single‐stranded conformational polymorphism (SSCP) analysis or sequencing. Results: Two of the siblings are monozygotic twins, and all had West syndrome with hypsarrthymia on EEG. MRI of the brain revealed periventricular nodules of cerebral gray‐matter intensity, typical for PH. Mutational analyses demonstrated a cytosine‐to‐thymidine missense mutation (c. C1286T), resulting in a threonine‐to‐methionine amino acid substitution in exon 9 of the FLNA gene. Conclusions: The association between PH and West syndrome, to our knowledge, has not been previously reported. Males with PH have been known to harbor FLNA mutations, although uniformly, they either show early lethality or survive and have a normal intellect. The current studies show that FLNA mutations can cause periventricular heterotopia, developmental regression, and West syndrome in male patients, suggesting that this type of FLNA mutation may contribute to severe neurologic deficits.
ISSN:0013-9580
1528-1167
DOI:10.1111/j.1528-1167.2006.00390.x