Bilateral periventricular heterotopias in an X-linked dominant transmission in a family with two affected males.
We report on the case of dizygotic twin boys, born prematurely to an asymptomatic mother. Bilateral periventricular heterotopias with enlarged ventricles were discovered at birth in both twins. One of the twins died prematurely of bronchopulmonary complications, and was shown to have several neuropathological anomalies (microgyria, thin corpus callosum, and reduced white matter). The surviving twin had mental retardation, without epilepsy. MRI of the mother showed asymptomatic periventricular heterotopias without ventricular enlargement. She had two affected daughters also with asymptomatic periventricular heterotopias. A point mutation in the last coding exon 48 of the Filamin A (FLNA) gene (7922c > t) was discovered on sequencing and segregated with the affected individuals. This family has a classical X-linked dominant BPNH pathology, with greater severity in males than females. The location of the FLNA mutation is discussed in light of the neuropathological anomalies and mental retardation in male patients.
Gérard-Blanluet
Marion
M
Medical genetics, Hôpital Robert Debré, Paris, France. marion.gerard@rdb.aphp.fr
Sheen
Volney
V
Machinis
Kalotina
K
Neal
Jason
J
Apse
Kira
K
Danan
Claude
C
Sinico
Martine
M
Brugières
Pierre
P
Mage
Katia
K
Ratsimbazafy
Lanto
L
Elbez
Annie
A
Janaud
Jean-Claude
JC
Amselem
Serge
S
Walsh
Christopher
C
Encha-Razavi
Férechté
F
D000595:Amino Acid Sequence; D001927:Brain Diseases / Q000150:complications / Q000235:genetics* / Q000473:pathology; D002552:Cerebral Ventricles; D002828:Choristoma / Q000150:complications / Q000235:genetics* / Q000473:pathology; D003285:Contractile Proteins / Q000235:genetics*; D005192:Family Health; D017809:Fatal Outcome; D005260:Female; D064448:Filamins; D005799:Genes, Dominant / Q000235:genetics; D040181:Genetic Diseases, X-Linked / Q000150:complications / Q000235:genetics; D006801:Humans; D007223:Infant; D008171:Lung Diseases / Q000150:complications; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D017386:Sequence Homology, Amino Acid; D014429:Twins, Dizygotic / Q000235:genetics
D003285:Contractile Proteins; D064448:Filamins; D008840:Microfilament Proteins