FaCD Online Syndrome Fact Sheet

Last updated: 02 Feb 2009

Name: Pulmonary Fibrosis, Idiopathic

Synonym: Hamman-Rich syndrome, Fibrocystic Pulmonary Dysplasia

Mode of Inheritance: AD / spor

Genes

SFTPA2, mapped to 10q22-q23
TERC, mapped to 3q21-q28
TERT, mapped to 5p15.33

Tumor features

lung/bronchial cancer

Non-tumor features

lung fibrosis

Comment

This disorder is characterized by an acute interstitial pneumonia leading to pulmonary fibrosis[1,2,7]. Overproduction of platelet-derived growth factor-beta may be an important etiological factor.

Lung cancer is a known complication of idiopathic pulmonary fibrosis[8] and has been observed in sporadic as well as familial cases. Swaye et al.[3] reported a family in which two affected brothers both developed lung cancer in their early fifties (1 case of adenocarcinoma, 1 case histology not published). Beaumont et al.[4] reported a family with pulmonary interstitial fibrosis in which 3 out of 5 affected relatives from 2 successive generations developed alveolar cell lung cancer. A similar association was published by McKusick and Fisher[5].

Wang et al[9] reported on co-segretation of lung cancer (bronchioalveolar carcinoma) and/or pulmonary fibrosis with a germline SFTPA2 mutation in a large family.

References

[1] Olson J, Colby TV, Elliott CG. Hamman-Rich syndrome revisited. Mayo Clin Proc 1990; 65:1538-1548.
[2] Rubin EH, Lubliner R. The Hamman-Rich syndrome: review of the literature and analysis of 15 cases. Medicine 1957; 36:397-463.
[3] Swaye P, Van Ordstrand HS, McCormack LJ, Wolpaw SE. Familial Hamman-Rich syndrome: report of eight cases. Dis Chest 1969; 55(1):7-12.
[4] Beaumont F, Jansen HM, Elema JD, ten Kate LP, Sluiter HJ. Simultaneous occurrence of pulmonary interstitial fibrosis and alveolar cell carcinoma in one family. Thorax 1981; 36:252-258.
[5] McKUSICK VA, FISHER AM. Congenital cystic disease of the lung with progressive pulmonary fibrosis and carcinomatosis. Annals of internal medicine 1958; 48(4):774-90.
[6] KOCH B. FAMILIAL FIBROCYSTIC PULMONARY DYSPLASIA: OBSERVATIONS IN ONE FAMILY. Canadian Medical Association journal 1965; 92():801-8.
[7] Meltzer EB, Noble PW. Idiopathic pulmonary fibrosis. Orphanet journal of rare diseases 2008; 3(1):8.
[8] Aubry MC, Myers JL, Douglas WW, Tazelaar HD, Washington Stephens TL, Hartman TE, Deschamps C, Pankratz VS. Primary pulmonary carcinoma in patients with idiopathic pulmonary fibrosis. Mayo Clinic proceedings. Mayo Clinic 2002; 77(8):763-70.
[9] Wang Y, Kuan PJ, Xing C, Cronkhite JT, Torres F, Rosenblatt RL, DiMaio JM, Kinch LN, Grishin NV, Garcia CK. Genetic defects in surfactant protein A2 are associated with pulmonary fibrosis and lung cancer.Am J Hum Genet. 2009 Jan;84(1):52-9