Skip to main content

Advertisement

SpringerLink
Log in

Identification of a Novel EIF2AK Variant and Genetics-Assisted Approach to Diagnosis of Pulmonary Capillary Hemangiomatosis

  • PULMONARY VASCULAR DISEASE
  • Published:
Lung Aims and scope Submit manuscript

Abstract

Pulmonary capillary hemangiomatosis (PCH) is an uncommon type of pulmonary vascular disease characterized by capillary proliferation and very poor prognosis owing to misdiagnosis and lack of effective therapeutic options. Mutations in the eukaryotic translation initiation factor 2α kinase 4 (EIF2AK4) gene have been reported in pulmonary veno-occlusive disease and PCH. In this report, we present a patient whose diagnosis of PCH was delayed by 2 ½ years despite prior surgical lung biopsy and clinical and laboratory findings suggestive of pulmonary hypertension. Genotyping revealed a novel likely pathogenic variant in the EIF2AK4 gene. Review of surgical lung biopsy performed 2 ½ years prior confirmed PCH histology along with constrictive bronchiolitis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Abbreviations

PCH:

Pulmonary capillary hemangiomatosis

PVOD:

Pulmonary veno-occlusive disease

EIF2AK4 :

Eukaryotic translation initiation factor 2α kinase 4

PAH:

Pulmonary arterial hypertension

RV:

Right ventricle

GGO:

Ground-glass opacities

CT:

Computed tomography

MRI:

Magnetic resonance imaging

BMF :

Blc2 modifying factor

References

  1. Holcomb BW Jr, Loyd JE, Ely EW, Johnson J, Robbins IM (2000) Pulmonary veno-occlusive disease: a case series and new observations. Chest 118:1671–1679

    PubMed  Google Scholar 

  2. O’Keefe MC, Post MD (2015) Pulmonary capillary hemangiomatosis: a rare cause of pulmonary hypertension. Arch Pathol Lab Med 139:274–277

    Article  Google Scholar 

  3. Morrell NW, Aldred MA, Chung WK et al (2019) Genetics and genomics of pulmonary arterial hypertension. Eur Respir J 53:1801899

    Article  CAS  Google Scholar 

  4. Abou Hassan OK, Haidar W, Arabi M et al (2019) Novel EIF2AK4 mutations in histologically proven pulmonary capillary hemangiomatosis and hereditary pulmonary arterial hypertension. BMC Med Genet 20:176

    Article  Google Scholar 

  5. Hadinnapola C, Bleda M, Haimel M et al (2017) Phenotypic characterization of EIF2AK4 mutation carriers in a large cohort of patients diagnosed clinically with pulmonary arterial hypertension. Circulation 136:2022–2033

    Article  Google Scholar 

  6. Eyries M, Montani D, Girerd B et al (2014) EIF2AK4 mutations cause pulmonary veno-occlusive disease, a recessive form of pulmonary hypertension. Nat Genet 46:65–69

    Article  CAS  Google Scholar 

  7. Ma L, Bao R (2015) Pulmonary capillary hemangiomatosis: a focus on the EIF2AK4 mutation in onset and pathogenesis. Appl Clin Genet 8:181–188

    Article  CAS  Google Scholar 

  8. Best DH, Sumner KL, Austin ED et al (2014) EIF2AK4 mutations in pulmonary capillary hemangiomatosis. Chest 145:231–236

    Article  CAS  Google Scholar 

  9. Galie N, Humbert M, Vachiery JL et al (2016) 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: the joint task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Heart J 37:67–119

    Article  Google Scholar 

  10. Shrine N, Guyatt AL, Erzurumluoglu AM et al (2019) New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries. Nat Genet 51:481–493

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by NIH Grant Number T32HL007605 (LMK, MRS).

Author information

Authors and Affiliations

  1. Department of Medicine, Section of Pulmonary and Critical Care Medicine, The University of Chicago, Chicago, IL, USA

    Lucas M. Kimmig, Matthew R. Stutz & Remzi Bag

  2. Department of Pathology, The University of Chicago, Chicago, IL, USA

    Aliya N. Husain

  3. Department of Internal Medicine, Universities of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany

    Lucas M. Kimmig

Authors
  1. Lucas M. Kimmig
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthew R. Stutz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Aliya N. Husain
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Remzi Bag
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

LMK, MRS, RB contributed to writing the manuscript, data curation and interpretation, ANH interpreted the pathology, provided the images, and edited the manuscript, RB provided conceptualization, RB provided oversight and edited the manuscript.

Corresponding author

Correspondence to Remzi Bag.

Ethics declarations

Conflict of interest

There are no competing interests for any author.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kimmig, L.M., Stutz, M.R., Husain, A.N. et al. Identification of a Novel EIF2AK Variant and Genetics-Assisted Approach to Diagnosis of Pulmonary Capillary Hemangiomatosis. Lung 200, 217–219 (2022). https://doi.org/10.1007/s00408-022-00517-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00408-022-00517-2

Search

Navigation