title: Genotype alone does not predict the clinical course of SFTPC deficiency in paediatric patients.
abstract: Patients with interstitial lung disease due to surfactant protein C (SFTPC) mutations are rare and not well characterised. We report on all subjects collected over a 15-year period in the kids-lung register with interstitial lung disease and a proven SFTPC mutation. We analysed clinical courses, interventions and outcomes, as well as histopathological and radiological interrelations. 17 patients (seven male) were followed over a median of 3 years (range 0.3-19). All patients were heterozygous carriers of autosomal dominant SFTPC mutations. Three mutations (p.L101P, p.E191 K and p.E191*) have not been described before in the context of surfactant protein C deficiency. Patients with alterations in the BRICHOS domain of the protein (amino acids 94-197) presented earlier. At follow-up, one patient was healthy (2 years), six patients were "sick-better" (2.8 years, range 0.8-19), seven patients were "sick-same" (6.5 years, 1.3-15.8) and three patients were "sick-worse" (0.3 years, 0.3-16.9). Radiological findings changed from ground-glass to increasing signs of fibrosis and cyst formation with increasing age. Empiric treatments had variable effects, also in patients with the same genotype. Prospective studies with randomised interventions are urgently needed and can best be performed in the framework of international registers.
authors: Department of Pediatric Pneumology, Hauner Children's Hospital, Ludwig-Maximilians University, Comprehensive Pneumology Center Munich (CPC-M), German Center for Lung Research (DZL), Munich, Germany.
authors: Carolin
authors: C
authors: Kröner
authors: Department of Pathology, Ludwig-Maximilians University, Munich, Germany.
authors: Simone
authors: S
authors: Reu
authors: Department of Pediatric Radiology, Hauner Children's Hospital, Ludwig-Maximilians University, Munich, Germany.
authors: Veronika
authors: V
authors: Teusch
authors: Department of Pediatric Pneumology, Hauner Children's Hospital, Ludwig-Maximilians University, Comprehensive Pneumology Center Munich (CPC-M), German Center for Lung Research (DZL), Munich, Germany.
authors: Andrea
authors: A
authors: Schams
authors: Department of Pediatric Pneumology, Hauner Children's Hospital, Ludwig-Maximilians University, Comprehensive Pneumology Center Munich (CPC-M), German Center for Lung Research (DZL), Munich, Germany.
authors: Ann-Christin
authors: AC
authors: Grimmelt
authors: Department of Pediatrics, HELIOS Klinikum Emil von Behring, Berlin, Germany.
authors: Michael
authors: M
authors: Barker
authors: Department of Pediatrics, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
authors: Joerg
authors: J
authors: Brand
authors: Department of Pediatric Pneumology, Marien-Hospital GmbH, Wesel, Germany.
authors: Monika
authors: M
authors: Gappa
authors: Department of Pediatric Pneumology, Clementinen Children's Hospital, Frankfurt am Main, Germany.
authors: Richard
authors: R
authors: Kitz
authors: Department of Pediatrics, Maastricht University Medical Center, Maastricht, Netherlands.
authors: Boris W
authors: BW
authors: Kramer
authors: Department of Pediatrics, St. Marien Hospital, Bonn, Germany.
authors: Lars
authors: L
authors: Lange
authors: Department of Pediatric Pneumology and Immunology, Charity University, Berlin, Germany.
authors: Susanne
authors: S
authors: Lau
authors: Pediatric Consultation Center Laurensberg, Aachen, Germany.
authors: Claus
authors: C
authors: Pfannenstiel
authors: Department of Pediatric Pneumology, University Hospital Leuven, Leuven, Belgium.
authors: Marijke
authors: M
authors: Proesmans
authors: Department of Pediatric Pneumology, Klinikum Oldenburg gGmbH, Medizinischer Campus Universität Oldenburg, Oldenburg, Germany.
authors: Jürgen
authors: J
authors: Seidenberg
authors: Department of Pediatric Pneumology, Gazi University Hospital, TR-Ankara, Turkey.
authors: Tugba
authors: T
authors: Sismanlar
authors: Department of Pediatric Pneumology, Gazi University Hospital, TR-Ankara, Turkey.
authors: Ayse Tana
authors: AT
authors: Aslan
authors: Department of Pediatric Pneumology, University Hospital Münster, Münster, Germany.
authors: Claudius
authors: C
authors: Werner
authors: Department of Pediatrics, Johann Wolfgang Goethe University, Frankfurt am Main, Germany.
authors: Stefan
authors: S
authors: Zielen
authors: Department of Pediatric Pneumology, Hauner Children's Hospital, Ludwig-Maximilians University, Comprehensive Pneumology Center Munich (CPC-M), German Center for Lung Research (DZL), Munich, Germany.
authors: Ralf
authors: R
authors: Zarbock
authors: Department of Pathology, Academic Teaching Hospital Bielefeld, Bielefeld, Germany.
authors: Frank
authors: F
authors: Brasch
authors: Institute of Laboratory Medicine and Human Genetics, Singen, Germany.
authors: Peter
authors: P
authors: Lohse
authors: Department of Pediatric Pneumology, Hauner Children's Hospital, Ludwig-Maximilians University, Comprehensive Pneumology Center Munich (CPC-M), German Center for Lung Research (DZL), Munich, Germany matthias.griese@med.uni-muenchen.de.
authors: Matthias
authors: M
authors: Griese
mesh_terms: D000293:Adolescent; D001706:Biopsy; D018893:Bronchoalveolar Lavage; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D005799:Genes, Dominant; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D017563:Lung Diseases, Interstitial / Q000235:genetics*; D008297:Male; D009154:Mutation; D011446:Prospective Studies; D037701:Pulmonary Surfactant-Associated Protein B / Q000378:metabolism; D037721:Pulmonary Surfactant-Associated Protein C / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; C489679:SFTPC protein, human