U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4(PFBMFT4)

MedGen UID:
903928
Concept ID:
C4225347
Disease or Syndrome
Synonym: PULMONARY FIBROSIS AND/OR BONE MARROW FAILURE SYNDROME, TELOMERE-RELATED, 4
 
Gene (location): PARN (16p13.12)
 
Monarch Initiative: MONDO:0014612
OMIM®: 616371

Definition

Dyskeratosis congenita and related telomere biology disorders (DC/TBD) are caused by impaired telomere maintenance resulting in short or very short telomeres. The phenotypic spectrum of telomere biology disorders is broad and includes individuals with classic dyskeratosis congenita (DC) as well as those with very short telomeres and an isolated physical finding. Classic DC is characterized by a triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia, although this may not be present in all individuals. People with DC/TBD are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome or acute myelogenous leukemia, solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), taurodontism, liver disease, gastrointestinal telangiectasias, and avascular necrosis of the hips or shoulders. Although most persons with DC/TBD have normal psychomotor development and normal neurologic function, significant developmental delay is present in both forms; additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome and Coats plus syndrome). Onset and progression of manifestations of DC/TBD vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF. [from GeneReviews]

Clinical features

From HPO
Cough
MedGen UID:
41325
Concept ID:
C0010200
Sign or Symptom
A sudden, audible expulsion of air from the lungs through a partially closed glottis, preceded by inhalation.
Pulmonary fibrosis
MedGen UID:
11028
Concept ID:
C0034069
Disease or Syndrome
Replacement of normal lung tissues by fibroblasts and collagen.
Honeycomb lung
MedGen UID:
910019
Concept ID:
C0241984
Disease or Syndrome
Honeycombing represents destroyed and fibrotic lung tissue containing numerous cystic airspaces with thick fibrous walls, representing the late stage of various lung diseases, with complete loss of acinar architecture. The cysts range in size from a few millimeters to several centimeters in diameter, have variable wall thickness, and are lined by metaplastic bronchiolar epithelium. On chest radiographs, honeycombing appears as closely approximated ring shadows, typically 3-10 mm in diameter with walls 1-3 mm in thickness, that resemble a honeycomb; the finding implies end-stage lung disease. On CT scans, the appearance is of clustered cystic air spaces, typically of comparable diameters on the order of 3-10 mm but occasionally as large as 2.5 cm. Honeycombing is usually subpleural and is characterized by well-defined walls. It is a CT feature of established pulmonary fibrosis. Because honeycombing is often considered specific for pulmonary fibrosis and is an important criterion in the diagnosis of usual interstitial pneumonia, the term should be used with care, as it may directly impact patient care.
Reduced forced vital capacity
MedGen UID:
337630
Concept ID:
C1846678
Finding
An abnormal reduction in the amount of air a person can expel following maximal inspiration.
Decreased DLCO
MedGen UID:
892993
Concept ID:
C4073175
Finding
Reduced ability of the lungs to transfer gas from inspired air to the bloodstream as measured by the diffusing capacity of the lungs for carbon monoxide (DLCO) test.
Reduced forced expiratory volume in one second
MedGen UID:
1687063
Concept ID:
C5139283
Finding
An abnormal reduction in the amount of air a person can forcefully expel in one second.
Premature graying of hair
MedGen UID:
75524
Concept ID:
C0263498
Finding
Development of gray hair at a younger than normal age.
Short telomere length
MedGen UID:
1627435
Concept ID:
C4531138
Anatomical Abnormality
An abnormal reduction in telomere length. Telomeres are non-coding, repetitive sequences of DNA at the ends of the chromosomes of eukaryotic cells which become shorter as cells divide, and when telomere attrition reaches its limit, cell proliferation arrest, senescence, and apoptosis can occur.

Professional guidelines

PubMed

Rajan SK, Cottin V, Dhar R, Danoff S, Flaherty KR, Brown KK, Mohan A, Renzoni E, Mohan M, Udwadia Z, Shenoy P, Currow D, Devraj A, Jankharia B, Kulshrestha R, Jones S, Ravaglia C, Quadrelli S, Iyer R, Dhooria S, Kolb M, Wells AU
Eur Respir J 2023 Mar;61(3) Epub 2023 Mar 30 doi: 10.1183/13993003.03187-2021. PMID: 36517177Free PMC Article
Raghu G, Remy-Jardin M, Richeldi L, Thomson CC, Inoue Y, Johkoh T, Kreuter M, Lynch DA, Maher TM, Martinez FJ, Molina-Molina M, Myers JL, Nicholson AG, Ryerson CJ, Strek ME, Troy LK, Wijsenbeek M, Mammen MJ, Hossain T, Bissell BD, Herman DD, Hon SM, Kheir F, Khor YH, Macrea M, Antoniou KM, Bouros D, Buendia-Roldan I, Caro F, Crestani B, Ho L, Morisset J, Olson AL, Podolanczuk A, Poletti V, Selman M, Ewing T, Jones S, Knight SL, Ghazipura M, Wilson KC
Am J Respir Crit Care Med 2022 May 1;205(9):e18-e47. doi: 10.1164/rccm.202202-0399ST. PMID: 35486072Free PMC Article
Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ, Behr J, Cottin V, Danoff SK, Morell F, Flaherty KR, Wells A, Martinez FJ, Azuma A, Bice TJ, Bouros D, Brown KK, Collard HR, Duggal A, Galvin L, Inoue Y, Jenkins RG, Johkoh T, Kazerooni EA, Kitaichi M, Knight SL, Mansour G, Nicholson AG, Pipavath SNJ, Buendía-Roldán I, Selman M, Travis WD, Walsh S, Wilson KC; American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society
Am J Respir Crit Care Med 2018 Sep 1;198(5):e44-e68. doi: 10.1164/rccm.201807-1255ST. PMID: 30168753

Recent clinical studies

Etiology

Strykowski R, Adegunsoye A
Immunol Allergy Clin North Am 2023 May;43(2):209-228. Epub 2023 Mar 3 doi: 10.1016/j.iac.2023.01.010. PMID: 37055085
Rajan SK, Cottin V, Dhar R, Danoff S, Flaherty KR, Brown KK, Mohan A, Renzoni E, Mohan M, Udwadia Z, Shenoy P, Currow D, Devraj A, Jankharia B, Kulshrestha R, Jones S, Ravaglia C, Quadrelli S, Iyer R, Dhooria S, Kolb M, Wells AU
Eur Respir J 2023 Mar;61(3) Epub 2023 Mar 30 doi: 10.1183/13993003.03187-2021. PMID: 36517177Free PMC Article
Tanni SE, Fabro AT, de Albuquerque A, Ferreira EVM, Verrastro CGY, Sawamura MVY, Ribeiro SM, Baldi BG
Expert Rev Respir Med 2021 Jun;15(6):791-803. Epub 2021 Apr 27 doi: 10.1080/17476348.2021.1916472. PMID: 33902377
Hewlett JC, Kropski JA, Blackwell TS
Matrix Biol 2018 Oct;71-72:112-127. Epub 2018 Apr 3 doi: 10.1016/j.matbio.2018.03.021. PMID: 29625182Free PMC Article
Meyer KC
Expert Rev Respir Med 2017 May;11(5):343-359. Epub 2017 Apr 10 doi: 10.1080/17476348.2017.1312346. PMID: 28345383

Diagnosis

Koudstaal T, Funke-Chambour M, Kreuter M, Molyneaux PL, Wijsenbeek MS
Trends Mol Med 2023 Dec;29(12):1076-1087. Epub 2023 Sep 14 doi: 10.1016/j.molmed.2023.08.010. PMID: 37716906
Rajan SK, Cottin V, Dhar R, Danoff S, Flaherty KR, Brown KK, Mohan A, Renzoni E, Mohan M, Udwadia Z, Shenoy P, Currow D, Devraj A, Jankharia B, Kulshrestha R, Jones S, Ravaglia C, Quadrelli S, Iyer R, Dhooria S, Kolb M, Wells AU
Eur Respir J 2023 Mar;61(3) Epub 2023 Mar 30 doi: 10.1183/13993003.03187-2021. PMID: 36517177Free PMC Article
Martinez FJ, Collard HR, Pardo A, Raghu G, Richeldi L, Selman M, Swigris JJ, Taniguchi H, Wells AU
Nat Rev Dis Primers 2017 Oct 20;3:17074. doi: 10.1038/nrdp.2017.74. PMID: 29052582
Richeldi L, Collard HR, Jones MG
Lancet 2017 May 13;389(10082):1941-1952. Epub 2017 Mar 30 doi: 10.1016/S0140-6736(17)30866-8. PMID: 28365056
Meyer KC
Expert Rev Respir Med 2017 May;11(5):343-359. Epub 2017 Apr 10 doi: 10.1080/17476348.2017.1312346. PMID: 28345383

Therapy

Glass DS, Grossfeld D, Renna HA, Agarwala P, Spiegler P, DeLeon J, Reiss AB
Clin Respir J 2022 Feb;16(2):84-96. Epub 2022 Jan 10 doi: 10.1111/crj.13466. PMID: 35001525Free PMC Article
Corte TJ, Lancaster L, Swigris JJ, Maher TM, Goldin JG, Palmer SM, Suda T, Ogura T, Minnich A, Zhan X, Tirucherai GS, Elpers B, Xiao H, Watanabe H, Smith RA, Charles ED, Fischer A
BMJ Open Respir Res 2021 Dec;8(1) doi: 10.1136/bmjresp-2021-001026. PMID: 34969771Free PMC Article
Finnerty JP, Ponnuswamy A, Dutta P, Abdelaziz A, Kamil H
BMC Pulm Med 2021 Dec 11;21(1):411. doi: 10.1186/s12890-021-01783-1. PMID: 34895203Free PMC Article
Heukels P, Moor CC, von der Thüsen JH, Wijsenbeek MS, Kool M
Respir Med 2019 Feb;147:79-91. Epub 2019 Jan 9 doi: 10.1016/j.rmed.2018.12.015. PMID: 30704705
Liu T, De Los Santos FG, Phan SH
Methods Mol Biol 2017;1627:27-42. doi: 10.1007/978-1-4939-7113-8_2. PMID: 28836192

Prognosis

Maher TM, Bendstrup E, Dron L, Langley J, Smith G, Khalid JM, Patel H, Kreuter M
Respir Res 2021 Jul 7;22(1):197. doi: 10.1186/s12931-021-01791-z. PMID: 34233665Free PMC Article
Luppi F, Kalluri M, Faverio P, Kreuter M, Ferrara G
Respir Res 2021 Apr 17;22(1):109. doi: 10.1186/s12931-021-01711-1. PMID: 33865386Free PMC Article
Meyer KC
Expert Rev Respir Med 2017 May;11(5):343-359. Epub 2017 Apr 10 doi: 10.1080/17476348.2017.1312346. PMID: 28345383
Hutchinson J, Fogarty A, Hubbard R, McKeever T
Eur Respir J 2015 Sep;46(3):795-806. Epub 2015 May 14 doi: 10.1183/09031936.00185114. PMID: 25976683
Ley B, Collard HR, King TE Jr
Am J Respir Crit Care Med 2011 Feb 15;183(4):431-40. Epub 2010 Oct 8 doi: 10.1164/rccm.201006-0894CI. PMID: 20935110

Clinical prediction guides

Cottin V, Hirani NA, Hotchkin DL, Nambiar AM, Ogura T, Otaola M, Skowasch D, Park JS, Poonyagariyagorn HK, Wuyts W, Wells AU
Eur Respir Rev 2018 Dec 31;27(150) Epub 2018 Dec 21 doi: 10.1183/16000617.0076-2018. PMID: 30578335Free PMC Article
Ley B, Ryerson CJ, Vittinghoff E, Ryu JH, Tomassetti S, Lee JS, Poletti V, Buccioli M, Elicker BM, Jones KD, King TE Jr, Collard HR
Ann Intern Med 2012 May 15;156(10):684-91. doi: 10.7326/0003-4819-156-10-201205150-00004. PMID: 22586007
Zisman DA, Keane MP, Belperio JA, Strieter RM, Lynch JP 3rd
Methods Mol Med 2005;117:3-44. doi: 10.1385/1-59259-940-0:003. PMID: 16130230Free PMC Article
Thannickal VJ, Toews GB, White ES, Lynch JP 3rd, Martinez FJ
Annu Rev Med 2004;55:395-417. doi: 10.1146/annurev.med.55.091902.103810. PMID: 14746528
Ashcroft T, Simpson JM, Timbrell V
J Clin Pathol 1988 Apr;41(4):467-70. doi: 10.1136/jcp.41.4.467. PMID: 3366935Free PMC Article

Recent systematic reviews

Ghazipura M, Mammen MJ, Herman DD, Hon SM, Bissell BD, Macrea M, Kheir F, Khor YH, Knight SL, Raghu G, Wilson KC, Hossain T
Ann Am Thorac Soc 2022 Jun;19(6):1040-1049. doi: 10.1513/AnnalsATS.202103-343OC. PMID: 35499854
Zisi D, Chryssanthopoulos C, Nanas S, Philippou A
Heart Lung 2022 May-Jun;53:89-98. Epub 2022 Feb 27 doi: 10.1016/j.hrtlng.2022.02.006. PMID: 35235877
Finnerty JP, Ponnuswamy A, Dutta P, Abdelaziz A, Kamil H
BMC Pulm Med 2021 Dec 11;21(1):411. doi: 10.1186/s12890-021-01783-1. PMID: 34895203Free PMC Article
Dowman L, Hill CJ, May A, Holland AE
Cochrane Database Syst Rev 2021 Feb 1;2(2):CD006322. doi: 10.1002/14651858.CD006322.pub4. PMID: 34559419Free PMC Article
Hutchinson J, Fogarty A, Hubbard R, McKeever T
Eur Respir J 2015 Sep;46(3):795-806. Epub 2015 May 14 doi: 10.1183/09031936.00185114. PMID: 25976683

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...