Bilateral periventricular heterotopias in an X-linked dominant transmission in a family with two affected males

• Published in: American journal of medical genetics. Part A 2006-05, Vol.140A (10), p.1041-1046
• Main Authors: Gérard-Blanluet, Marion, Sheen, Volney, Machinis, Kalotina, Neal, Jason, Apse, Kira, Danan, Claude, Sinico, Martine, Brugières, Pierre, Mage, Katia, Ratsimbazafy, Lanto, Elbez, Annie, Janaud, Jean-Claude, Amselem, Serge, Walsh, Christopher, Encha-Razavi, Férechté
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Biological and medical sciences; Brain Diseases; Brain Diseases - complications; Brain Diseases - genetics; Brain Diseases - pathology; Cerebral Ventricles; Choristoma; Choristoma - complications; Choristoma - genetics; Choristoma - pathology; Contractile Proteins; Contractile Proteins - genetics; Family Health; Fatal Outcome; Female; Filamins; Genes, Dominant; Genes, Dominant - genetics; Genetic Diseases, X-Linked; Genetic Diseases, X-Linked - complications; Genetic Diseases, X-Linked - genetics; Genetics; Human genetics; Humans; Infant; Life Sciences; Lung Diseases; Lung Diseases - complications; Male; Medical genetics; Medical sciences; Microfilament Proteins; Microfilament Proteins - genetics; Molecular Sequence Data; neuronal migration disorder; Pedigree; periventricular heterotopias; Point Mutation; Sequence Homology, Amino Acid; Twins, Dizygotic; Twins, Dizygotic - genetics
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.31197

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. © 2006 Wiley‐Liss, Inc.