title: Hepatopulmonary syndrome is a frequent cause of dyspnea in the short telomere disorders.
abstract: BACKGROUND
  Telomere syndromes have their most common manifestation in idiopathic pulmonary fibrosis and emphysema. The short telomere defect in these patients may manifest systemically as bone marrow failure and liver disease. We sought to understand the causes of dyspnea in telomerase and telomere gene mutation carriers who have no parenchymal lung disease.
  
  
  METHODS
  Clinical and pathologic data were reviewed as part of a Johns Hopkins-based natural history study of short telomere syndromes including dyskeratosis congenita.
  
  
  RESULTS
  Hepatopulmonary syndrome (HPS) was diagnosed in nine of 42 cases (21%). Their age at presentation was significantly younger than that of cases initially presenting with pulmonary fibrosis and emphysema (median, 25 years vs 55 years; P < .001). Cases had evidence of intra- and extrapulmonary arteriovascular malformations that caused shunt physiology. Nodular regenerative hyperplasia was the most frequent histopathologic abnormality, and it was seen in the absence of cirrhosis. Dyspnea and portal hypertension were progressive, and the median time to death or liver transplantation was 6 years (range, 4-10 years; n = 6). In cases that underwent liver transplantation, dyspnea and hypoxia improved, but pulmonary fibrosis subsequently developed.
  
  
  CONCLUSIONS
  This report identifies HPS as a frequent cause of dyspnea in telomerase and telomere gene mutation carriers. While it usually precedes the development of parenchymal lung disease, HPS may also co-occur with pulmonary fibrosis and emphysema. Recognizing this genetic diagnosis is critical for management, especially in the lung and liver transplantation setting.
authors.affiliation: Department of Oncology, Baltimore, MD.
authors.forename: Amany I
authors.initials: AI
authors.lastname: Gorgy
authors.affiliation: Department of Medicine, Baltimore, MD.
authors.forename: Naudia L
authors.initials: NL
authors.lastname: Jonassaint
authors.affiliation: Department of Oncology, Baltimore, MD; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Stanley
authors.affiliation: Department of Medicine, Baltimore, MD.
authors.forename: Ayman
authors.initials: A
authors.lastname: Koteish
authors.affiliation: Department of Oncology, Baltimore, MD; Department of Medicine, Baltimore, MD.
authors.forename: Amy E
authors.initials: AE
authors.lastname: DeZern
authors.affiliation: Department of Division of Allergy and Immunology, Massachusetts General Hospital for Children, Boston, MA.
authors.forename: Jolan E
authors.initials: JE
authors.lastname: Walter
authors.affiliation: Department of Pathology, Baltimore, MD.
authors.forename: Sabrina C
authors.initials: SC
authors.lastname: Sopha
authors.affiliation: Department of Medicine, Baltimore, MD.
authors.forename: James P
authors.initials: JP
authors.lastname: Hamilton
authors.affiliation: Department of Pediatrics, Baltimore, MD; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
authors.forename: Julie
authors.initials: J
authors.lastname: Hoover-Fong
authors.affiliation: Department of Oncology, Baltimore, MD.
authors.forename: Allen R
authors.initials: AR
authors.lastname: Chen
authors.affiliation: Department of Pathology, Baltimore, MD.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Anders
authors.affiliation: Department of Radiology, Baltimore, MD.
authors.forename: Ihab R
authors.initials: IR
authors.lastname: Kamel
authors.affiliation: Department of Oncology, Baltimore, MD; Department of Pathology, Baltimore, MD; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD. Electronic address: marmani1@jhmi.edu.
authors.forename: Mary
authors.initials: M
authors.lastname: Armanios
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004417:Dyspnea / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D005260:Female; D020065:Hepatopulmonary Syndrome / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012189:Retrospective Studies; D019098:Telomerase / Q000235:genetics; D016615:Telomere / Q000235:genetics*; D059505:Telomere Homeostasis
chemical_list: D019098:Telomerase