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Correspondence |

Familial Chronic Thromboembolic Pulmonary Hypertension in a Pair of Japanese Brothers FREE TO VIEW

Masaharu Kataoka, MD, PhD; Yuichi Momose, MD; Yuki Aimi, MHS; Keiichi Fukuda, MD, PhD; Shinobu Gamou, PhD; Toru Satoh, MD, PhD
Author and Funding Information

FINANCIAL/NONFINANCIAL DISCLOSURES: None declared.

aDepartment of Cardiology, Keio University School of Medicine, Tokyo, Japan

bDivision of Cardiology, Department of Medicine, Kyorin University School of Medicine, Tokyo, Japan

cCenter for Comprehensive Regional Collaboration, Kyorin University School of Medicine, Tokyo, Japan

CORRESPONDENCE TO: Masaharu Kataoka, MD, PhD, Department of Cardiology, Keio University School of Medicine, Shinanomachi 35, Shinjuku-ku, Tokyo, 160-8582, Japan


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;150(3):748-749. doi:10.1016/j.chest.2016.06.021
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We read the article by Desmarais and Elliott, published in a recent issue of CHEST (April 2016), with great interest. In their report, the authors describe a familial chronic thromboembolic pulmonary hypertension (CTEPH) pair consisting of a 54-year-old woman and her maternal aunt, which represents the first description of familial CTEPH. Herein, we describe another familial CTEPH pair consisting of two Japanese brothers who are 2 years apart in age.

Figure 1 shows the patients’ family tree. Case 1 is the older brother, who received a diagnosis of CTEPH at 60 years of age. His mean pulmonary arterial pressure (PAP) was 40 mm Hg at diagnosis. He had no history of DVT or pulmonary embolism. He also did not have thrombophilia and underwent percutaneous transluminal pulmonary angioplasty (PTPA), also known as balloon pulmonary angioplasty, at 61 years of age. His mean PAP was 16 mm Hg after the PTPA, suggesting a significant hemodynamic improvement.

Figure Jump LinkFigure 1 Patients’ family tree. Red squares represent the two individuals (brothers) with chronic thromboembolic pulmonary hypertension (CTEPH) in this family. Their thrombophilia was excluded by testing of parotein C, protein S, lupus anticoagulant, anticardiolipin antibody, anticardiolipin β2-glycoprotein I antibody, and antithrombin III. Although the younger brother (case 2) had experienced DVT and acute pulmonary embolism before the diagnosis of CTEPH, neither of the brothers had any of the other known risk factors for CTEPH (eg, splenectomy). Their father died of pancreatic cancer, and one of their maternal uncles died of stomach cancer. Furthermore, in family members other than these two brothers, there were no cases with a evident history of CTEPH, no deaths suspicious for CTEPH, no members who had suspicious but unproven CTEPH (eg, right-sided heart failure in a patient with a history of pulmonary embolism), no members who had DVT and/or pulmonary embolism, and no members with postphlebitic syndrome.Grahic Jump Location

Case 2 is the younger brother, who experienced DVT and acute pulmonary embolism at 47 years of age. This brother also did not have thrombophilia. He developed leg edema at 55 years of age and, after detailed examination, was diagnosed with CTEPH. His mean PAP was 42 mm Hg at diagnosis. He underwent pulmonary endarterectomy at 56 years of age and additional PTPA for residual pulmonary hypertension at 58 years of age. His mean PAP was 34 mm Hg before the PTPA and improved to 26 mm Hg at follow-up after additional PTPA.

As adults, these brothers, both with CTEPH, have different lifestyles and daily habits, suggesting that the pathogenesis of their CTEPH could be related to common environmental factors during their childhood or, more likely, unknown genetic mutations.

We are currently following up 160 patients with CTEPH; only the two reported here (1.25%) have familial CTEPH. Up until April 2016, we had investigated mutations in the bone morphogenetic protein receptor type II (BMPR2) gene, which is related to the pathogenesis of pulmonary arterial hypertension, in 236 patients with pulmonary hypertension; this group included 85 patients with CTEPH, as described previously. No significant mutations were found in the BMPR2 gene in patients with CTEPH, including the brothers in the current report.

The cases of CTEPH as described by Desmarais and Elliott and the two brothers in the current report provide evidence that familial CTEPH exists, although it seems to be rare. In Japan, at least, the downward trend in the birth rate may mask the actual prevalence of familial CTEPH. By undertaking a worldwide collaboration to study more families with CTEPH, we can expect to elucidate the possible molecular mechanisms involved in the pathogenesis of CTEPH, including currently unknown genetic factors.

References

Desmarais J. .Elliott C.G. . Familial chronic thromboembolic pulmonary hypertension. Chest. 2016;149:e99-e101 [PubMed]journal. [CrossRef] [PubMed]
 
Kataoka M. .Aimi Y. .Yanagisawa R. .et al Alu-mediated nonallelic homologous and nonhomologous recombination in the BMPR2 gene in heritable pulmonary arterial hypertension. Genet Med. 2013;15:941-947 [PubMed]journal. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1 Patients’ family tree. Red squares represent the two individuals (brothers) with chronic thromboembolic pulmonary hypertension (CTEPH) in this family. Their thrombophilia was excluded by testing of parotein C, protein S, lupus anticoagulant, anticardiolipin antibody, anticardiolipin β2-glycoprotein I antibody, and antithrombin III. Although the younger brother (case 2) had experienced DVT and acute pulmonary embolism before the diagnosis of CTEPH, neither of the brothers had any of the other known risk factors for CTEPH (eg, splenectomy). Their father died of pancreatic cancer, and one of their maternal uncles died of stomach cancer. Furthermore, in family members other than these two brothers, there were no cases with a evident history of CTEPH, no deaths suspicious for CTEPH, no members who had suspicious but unproven CTEPH (eg, right-sided heart failure in a patient with a history of pulmonary embolism), no members who had DVT and/or pulmonary embolism, and no members with postphlebitic syndrome.Grahic Jump Location

Tables

References

Desmarais J. .Elliott C.G. . Familial chronic thromboembolic pulmonary hypertension. Chest. 2016;149:e99-e101 [PubMed]journal. [CrossRef] [PubMed]
 
Kataoka M. .Aimi Y. .Yanagisawa R. .et al Alu-mediated nonallelic homologous and nonhomologous recombination in the BMPR2 gene in heritable pulmonary arterial hypertension. Genet Med. 2013;15:941-947 [PubMed]journal. [CrossRef] [PubMed]
 
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