Congenital Surfactant Deficiency

Congenital Surfactant Deficiency

Billie Fyfe, MD

Eileen McKay, MD

Lobular remodeling, interstitial widening, increased smooth muscle image, and cholesterol clefts image are shown in a 23 month old with a SFTPC mutation.

Lung biopsy shows early remodeling, pneumocyte hyperplasia, and foamy alveolar macrophages image as described in patients with mutations of SFTPB and ABCA3.



  • Surfactant dysfunction disorder

  • Congenital alveolar proteinosis

    • Often used incorrectly as a synonym

      • Proteinosis histology not specific to surfactant dysfunction and is one of many histologic patterns seen in this disease


Normal Surfactant Homeostasis

  • Synthesized, packaged, and secreted by type 2 pneumocytes via lamellar bodies, surfactant reduces surface tension at air-liquid interface in the alveoli

    • Surfactant proteins B (SP-B) and C (SP-C) interact with surfactant phospholipids to aid organization, spreading, and stability of surfactant

      • SP-B also important for processing proSP-C to SP-C

    • ABCA3 aids translocation of substances (especially lipids) across cell membranes

      • Expressed on outer membrane of lamellar bodies

      • Thought to play a role in maturation of lamellar bodies

    • TTF-1 protein important for lung development and expression of SP-B, SP-C, and ABCA3

Inheritance Patterns and Mutations

  • SFTPB mutations: Autosomal recessive

    • Gene localized on chromosome 2

    • > 30 loss of function mutations leading to partial or complete absence of SP-B

    • Most common mutation (70% of cases) is GAA substitution for C in codon 121 (a.k.a. 121ins2)

      • Carrier frequency: 1 per 1,000 people in general population

    • Loss of SP-B → improper SP-C processing with accumulation of proSP-C in type 2 pneumocytes and alveoli contributing to surfactant dysfunction and clinical disease

  • SFTPC mutations: Autosomal dominant with variable penetrance and sporadic (55%) mutations

    • Gene localized on chromosome 8

    • > 35 dominantly expressed mutations leading to misfolded proSP-C that accumulates in type 2 pneumocytes

      • Leads to misfolded protein response, cell stress injury, and apoptosis

    • Most common mutation (25% of cases) is threonine for isoleucine in codon 73 (a.k.a. I73T)

  • ABCA3 mutations: Autosomal recessive

    • Gene localized on chromosome16

    • > 70 recessive mutations

  • NKX2-1 mutations: Autosomal dominant

Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Congenital Surfactant Deficiency

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