Lung disease associated with periventricular nodular heterotopia and an FLNA mutation.
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.
Masurel-Paulet
Alice
A
Centre de Génétique, Hôpital d'Enfants, 10 bd Maréchal de Lattre de Tassigny, 21034 Dijon Cedex, France.
Haan
Eric
E
Thompson
Elizabeth M
EM
Goizet
Cyril
C
Thauvin-Robinet
Christel
C
Tai
Andrew
A
Kennedy
Declan
D
Smith
Greg
G
Khong
Teck Yee
TY
Solé
Guilhem
G
Guerineau
Elodie
E
Coupry
Isabelle
I
Huet
Frédéric
F
Robertson
Stephen
S
Faivre
Laurence
L
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*
D003285:Contractile Proteins; D064448:Filamins; D008840:Microfilament Proteins