Lindsay C Burrage1, R Paul Guillerman2, Shailendra Das3, Shipra Singh4, Deborah A Schady5, Shaine A Morris6, Magdalena Walkiewicz7, Marc G Schecter8, Jeffrey S Heinle9, Timothy E Lotze10, Seema R Lalani1, George B Mallory11. 1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX; Texas Children's Hospital, Houston, TX. 2. Department of Radiology, Baylor College of Medicine, Houston, TX. 3. Section of Pediatric Pulmonology, Department of Pediatrics, Baylor College of Medicine, Houston, TX. 4. Division of Pulmonology, Department of Pediatrics, State University of New York-Buffalo, Buffalo, NY. 5. Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX. 6. Section of Pediatric Cardiology, Department of Pediatrics, Baylor College of Medicine, Houston, TX. 7. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX. 8. Division of Pulmonary Medicine, Department of Pediatrics, University of Cincinnati School of Medicine, Cincinnati, OH. 9. Division of Congenital Heart Surgery, Department of Surgery, Baylor College of Medicine, Houston, TX. 10. Section of Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, TX. 11. Section of Pediatric Pulmonology, Department of Pediatrics, Baylor College of Medicine, Houston, TX. Electronic address: gbmallor@texaschildrens.org.
Abstract
OBJECTIVE: To describe a series of patients with pathogenic variants in FLNA and progressive lung disease necessitating lung transplantation. STUDY DESIGN: We conducted a retrospective chart review of 6 female infants with heterozygous presumed loss-of-function pathogenic variants in FLNA whose initial presentation was early and progressive respiratory failure. RESULTS: Each patient received lung transplantation at an average age of 11 months (range, 5-15 months). All patients had pulmonary arterial hypertension and chronic respiratory failure requiring tracheostomy and escalating levels of ventilator support before transplantation. All 6 patients survived initial lung transplantation; however, 1 patient died after a subsequent heart-lung transplant. The remaining 5 patients are living unrestricted lives on chronic immunosuppression at most recent follow-up (range, 19 months to 11.3 years post-transplantation). However, in all patients, severe ascending aortic dilation has been observed with aortic regurgitation. CONCLUSIONS: Respiratory failure secondary to progressive obstructive lung disease during infancy may be the presenting phenotype of FLNA-associated periventricular nodular heterotopia. We describe a cohort of patients with progressive respiratory failure related to a pathogenic variant in FLNA and present lung transplantation as a viable therapeutic option for this group of patients.
OBJECTIVE: To describe a series of patients with pathogenic variants in FLNA and progressive lung disease necessitating lung transplantation. STUDY DESIGN: We conducted a retrospective chart review of 6 female infants with heterozygous presumed loss-of-function pathogenic variants in FLNA whose initial presentation was early and progressive respiratory failure. RESULTS: Each patient received lung transplantation at an average age of 11 months (range, 5-15 months). All patients had pulmonary arterial hypertension and chronic respiratory failure requiring tracheostomy and escalating levels of ventilator support before transplantation. All 6 patients survived initial lung transplantation; however, 1 patient died after a subsequent heart-lung transplant. The remaining 5 patients are living unrestricted lives on chronic immunosuppression at most recent follow-up (range, 19 months to 11.3 years post-transplantation). However, in all patients, severe ascending aortic dilation has been observed with aortic regurgitation. CONCLUSIONS:Respiratory failure secondary to progressive obstructive lung disease during infancy may be the presenting phenotype of FLNA-associated periventricular nodular heterotopia. We describe a cohort of patients with progressive respiratory failure related to a pathogenic variant in FLNA and present lung transplantation as a viable therapeutic option for this group of patients.
Authors: Eyal Reinstein; Sophia Frentz; Tim Morgan; Sixto García-Miñaúr; Richard J Leventer; George McGillivray; Mitchel Pariani; Anthony van der Steen; Michael Pope; Muriel Holder-Espinasse; Richard Scott; Elizabeth M Thompson; Terry Robertson; Brian Coppin; Robert Siegel; Montserrat Bret Zurita; Jose I Rodríguez; Carmen Morales; Yuri Rodrigues; Joaquín Arcas; Anand Saggar; Margaret Horton; Elaine Zackai; John M Graham; David L Rimoin; Stephen P Robertson Journal: Eur J Hum Genet Date: 2012-10-03 Impact factor: 4.246
Authors: J W Fox; E D Lamperti; Y Z Ekşioğlu; S E Hong; Y Feng; D A Graham; I E Scheffer; W B Dobyns; B A Hirsch; R A Radtke; S F Berkovic; P R Huttenlocher; C A Walsh Journal: Neuron Date: 1998-12 Impact factor: 17.173
Authors: G Solé; I Coupry; C Rooryck; E Guérineau; F Martins; S Devés; C Hubert; N Souakri; O Boute; C Marchal; L Faivre; E Landré; S Debruxelles; A Dieux-Coeslier; C Boulay; S Chassagnon; V Michel; M-C Routon; A Toutain; N Philip; D Lacombe; L Villard; B Arveiler; C Goizet Journal: J Neurol Neurosurg Psychiatry Date: 2009-12 Impact factor: 10.154
Authors: Jan J J Aalberts; J Peter van Tintelen; Toon Oomen; Jorieke E H Bergman; Dicky J J Halley; Jan D H Jongbloed; Albert J H Suurmeijer; Maarten P van den Berg Journal: Am J Med Genet A Date: 2013-11-15 Impact factor: 2.802
Authors: Annagiusi Gargiulo; Renata Auricchio; Maria Vittoria Barone; Gabriella Cotugno; William Reardon; Peter J Milla; Andrea Ballabio; Alfredo Ciccodicola; Alberto Auricchio Journal: Am J Hum Genet Date: 2007-02-26 Impact factor: 11.025
Authors: Max Lange; Burkhard Kasper; Axel Bohring; Frank Rutsch; Gerhard Kluger; Sabine Hoffjan; Stephanie Spranger; Anne Behnecke; Andreas Ferbert; Andreas Hahn; Barbara Oehl-Jaschkowitz; Luitgard Graul-Neumann; Katharina Diepold; Isolde Schreyer; Matthias K Bernhard; Franziska Mueller; Ulrike Siebers-Renelt; Ana Beleza-Meireles; Goekhan Uyanik; Sandra Janssens; Eugen Boltshauser; Juergen Winkler; Gerhard Schuierer; Ute Hehr Journal: Orphanet J Rare Dis Date: 2015-10-15 Impact factor: 4.123
Authors: Safa Eltahir; Khalid S Ahmad; Mohammed M Al-Balawi; Hussien Bukhamsien; Khalid Al-Mobaireek; Wadha Alotaibi; Abdullah Al-Shamrani Journal: J Med Case Rep Date: 2016-04-18
Authors: Amit S Shah; Emily D Black; Dawn M Simon; Michael J Gambello; Kathryn B Garber; Glen J Iannucci; Erica L Riedesel; Ajay S Kasi Journal: Pediatr Allergy Immunol Pulmonol Date: 2021-03 Impact factor: 1.349
Authors: Laura M Tanner; Shinji Kunishima; Elina Lehtinen; Tuukka Helin; Kirsi Volmonen; Riitta Lassila; Minna Pöyhönen Journal: Am J Med Genet A Date: 2022-02-14 Impact factor: 2.578