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: Alice Masurel-Paulet, Eric Haan, Elizabeth M Thompson, Cyril Goizet, Christel Thauvin-Robinet, Andrew Tai, Declan Kennedy, Greg Smith, Teck Yee Khong, Guilhem Solé, Elodie Guerineau, Isabelle Coupry, Frédéric Huet, Stephen Robertson, Laurence Faivre
• Journal: European journal of medical genetics (Eur J Med Genet) 2011 Jan-Feb Vol. 54 Issue 1 Pg. 25-8 ISSN: 1878-0849 [Electronic] Netherlands
• PMID: 20888935 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Chemical References

• Contractile Proteins
• Filamins
• Microfilament Proteins

Topics

• Abnormalities, Multiple (genetics, pathology)
• Child
• Contractile Proteins (genetics)
• DNA Mutational Analysis
• Filamins
• Humans
• Lung Diseases (congenital)
• Male
• Microfilament Proteins (genetics)
• Mutation
• Periventricular Nodular Heterotopia (pathology)