title: Lung disease associated with periventricular nodular heterotopia and an FLNA mutation.
abstract: X-linked periventricular nodular heterotopia (PH) is a neuronal migration disorder caused by mutations in the gene encoding filamin A (FLNA). High phenotypic diversity, ranging from PH to otopalatodigital syndrome and frontometaphyseal dysplasia has been described in association with FLNA mutations. Extra-neurological features including cardiovascular abnormalities, coagulopathy, skeletal dysplasia and joint hypermobility have sometimes been described in patients with PH. Respiratory manifestations have not been associated with FLNA disorders with the exception of tracheal stenosis and pulmonary hypoplasia associated with frontometaphyseal dysplasia and Melnick-Needles syndrome. Here, we report on a male patient aged 6 years presenting with a mosaic nonsense mutation c.994delG within the FLNA gene, PH and severe congenital lung disease comprising bilateral atelectasis, lung cysts, tracheobronchomalacia, pulmonary arterial hypertension and long-term oxygen dependence; histology of resected lung showed panpulmonary emphysema with marked reduction of bronchial cartilage. Rare male patients with PH and FLNA mutations have already been reported, usually with early lethality. These observations suggest the possibility of a link between FLNA mutations and congenital lung disease. A prospective study of patients with PH and FLNA mutations would be helpful in order to test this hypothesis.
authors.affiliation: Centre de Génétique, Hôpital d'Enfants, 10 bd Maréchal de Lattre de Tassigny, 21034 Dijon Cedex, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Masurel-Paulet
authors.forename: Eric
authors.initials: E
authors.lastname: Haan
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Thompson
authors.forename: Cyril
authors.initials: C
authors.lastname: Goizet
authors.forename: Christel
authors.initials: C
authors.lastname: Thauvin-Robinet
authors.forename: Andrew
authors.initials: A
authors.lastname: Tai
authors.forename: Declan
authors.initials: D
authors.lastname: Kennedy
authors.forename: Greg
authors.initials: G
authors.lastname: Smith
authors.forename: Teck Yee
authors.initials: TY
authors.lastname: Khong
authors.forename: Guilhem
authors.initials: G
authors.lastname: Solé
authors.forename: Elodie
authors.initials: E
authors.lastname: Guerineau
authors.forename: Isabelle
authors.initials: I
authors.lastname: Coupry
authors.forename: Frédéric
authors.initials: F
authors.lastname: Huet
authors.forename: Stephen
authors.initials: S
authors.lastname: Robertson
authors.forename: Laurence
authors.initials: L
authors.lastname: Faivre
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D002648:Child; D003285:Contractile Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D064448:Filamins; D006801:Humans; D008171:Lung Diseases / Q000151:congenital*; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D009154:Mutation; D054091:Periventricular Nodular Heterotopia / Q000473:pathology*
chemical_list: D003285:Contractile Proteins; D064448:Filamins; D008840:Microfilament Proteins