Genotype alone does not predict the clinical course of SFTPC deficiency in paediatric patients

Eur Respir J. 2015 Jul;46(1):197-206. doi: 10.1183/09031936.00129414. Epub 2015 Feb 5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Biopsy
  • Bronchoalveolar Lavage
  • Child
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • Genes, Dominant
  • Genotype
  • Heterozygote
  • Humans
  • Infant
  • Infant, Newborn
  • Lung Diseases, Interstitial / genetics*
  • Male
  • Mutation*
  • Prospective Studies
  • Pulmonary Surfactant-Associated Protein B / metabolism
  • Pulmonary Surfactant-Associated Protein C / deficiency*
  • Pulmonary Surfactant-Associated Protein C / genetics*
  • Pulmonary Surfactant-Associated Protein C / metabolism
  • Retrospective Studies

Substances

  • Pulmonary Surfactant-Associated Protein B
  • Pulmonary Surfactant-Associated Protein C
  • SFTPC protein, human