Birt-Hogg-Dube Syndrome (BHDS) Differential Diagnoses

1. Birt AR, Hogg GR, Dube WJ. Hereditary multiple fibrofolliculomas with trichodiscomas and acrochordons. Arch Dermatol. 1977 Dec. 113(12):1674-7. [QxMD MEDLINE Link].

2. De la Torre C, Ocampo C, Doval IG, Losada A, Cruces MJ. Acrochordons are not a component of the Birt-Hogg-Dubé syndrome: does this syndrome exist? Case reports and review of the literature. Am J Dermatopathol. 1999 Aug. 21(4):369-74. [QxMD MEDLINE Link].

3. Fujita WH, Barr RJ, Headley JL. Multiple fibrofolliculomas with trichodiscomas and acrochordons. Arch Dermatol. 1981 Jan. 117(1):32-5. [QxMD MEDLINE Link].

4. Haimowitz JE, Halpern AC, Heymann WR. Multiple, hereditary dome-shaped papules and acrochordons. Birt-Hogg-Dubé syndrome. Arch Dermatol. 1997 Sep. 133(9):1163, 1166. [QxMD MEDLINE Link].

5. Starink TM, Kisch LS, Meijer CJ. Familial multiple trichodiscomas. A clinicopathologic study. Arch Dermatol. 1985 Jul. 121(7):888-91. [QxMD MEDLINE Link].

6. Ubogy-Rainey Z, James WD, Lupton GP, Rodman OG. Fibrofolliculomas, trichodiscomas, and acrochordons: the Birt-Hogg-Dubé syndrome. J Am Acad Dermatol. 1987 Feb. 16(2 Pt 2):452-7. [QxMD MEDLINE Link].

7. Welsch MJ, Krunic A, Medenica MM. Birt-Hogg-Dubé Syndrome. Int J Dermatol. 2005 Aug. 44(8):668-73. [QxMD MEDLINE Link].

8. Junkins-Hopkins JM, Cooper PH. Multiple perifollicular fibromas: report of a case and analysis of the literature. J Cutan Pathol. 1994 Oct. 21(5):467-71. [QxMD MEDLINE Link].

9. Schmidt LS, Linehan WM. Clinical Features, Genetics and Potential Therapeutic Approaches for Birt-Hogg-Dubé Syndrome. Expert Opin Orphan Drugs. 2015. 3 (1):15-29. [QxMD MEDLINE Link].

10. Adley BP, Smith ND, Navar XJ. Birt-Hogg-Dube syndrome: clinicpathologic findings and genetic alterations. Arch Pathol Lab Med. 2006. December 130 (12):1865-1870.

11. Roth JS, Rabinowitz AD, Benson M, Grossman ME. Bilateral renal cell carcinoma in the Birt-Hogg-Dubé syndrome. J Am Acad Dermatol. 1993 Dec. 29(6):1055-6. [QxMD MEDLINE Link].

12. Schmidt LS, Warren MB, Nickerson ML, et al. Birt-Hogg-Dubé syndrome, a genodermatosis associated with spontaneous pneumothorax and kidney neoplasia, maps to chromosome 17p11.2. Am J Hum Genet. 2001 Oct. 69(4):876-82. [QxMD MEDLINE Link]. [Full Text].

13. Toro JR, Glenn G, Duray P, et al. Birt-Hogg-Dubé syndrome: a novel marker of kidney neoplasia. Arch Dermatol. 1999 Oct. 135(10):1195-202. [QxMD MEDLINE Link].

14. Tobino K, Seyama K. Birt-Hogg-Dubé syndrome with renal angiomyolipoma. Intern Med. 2012. 51(10):1279-80.

15. Mallipeddi R, Pichert G, Whittaker S. Birt-Hogg-Dubé syndrome with a renal angiomyolipoma: further evidence of a relationship between Birt Hogg-Dubé syndrome and tuberous sclerosis complex. Byrne Australas J Dermatol. 2012 May. 53(2):151-4.

16. Lin Z, Gong K, Pang B, Zeng C, Zhang D. Birt-Hogg-Dubé syndrome with clear cell renal cell carcinoma in a Chinese family. Intern Med. 2014. 53 (24):2825-8. [QxMD MEDLINE Link].

17. Pavlovich CP, Walther MM, Eyler RA, Hewitt SM, Zbar B, Linehan WM, et al. Renal tumors in the Birt-Hogg-Dubé syndrome. Am J Surg Pathol. 2002 Dec. 26 (12):1542-52. [QxMD MEDLINE Link].

18. Pavlovich CP, Grubb RL 3rd, Hurley K, Glenn GM, Toro J, Schmidt LS, et al. Evaluation and management of renal tumors in the Birt-Hogg-Dubé syndrome. J Urol. 2005 May. 173 (5):1482-6. [QxMD MEDLINE Link].

19. Kennedy JM, Wang X, Plouffe KR, Dhanasekaran SM, Hafez K, Palapattu GS, et al. Clinical and morphologic review of 60 hereditary renal tumors from 30 hereditary renal cell carcinoma syndrome patients: lessons from a contemporary single institution series. Med Oncol. 2019 Jul 22. 36 (9):74. [QxMD MEDLINE Link].

20. Houweling AC, Gijezen LM, Jonker MA, et al. Renal cancer and pneumothorax risk in Birt-Hogg-Dubé syndrome; an analysis of 115 FLCN mutation carriers from 35 BHD families. Br J Cancer. 2011 Dec 6. 105(12):1912-9. [QxMD MEDLINE Link]. [Full Text].

21. Schmidt LS, Nickerson ML, Warren MB, et al. Germline BHD-mutation spectrum and phenotype analysis of a large cohort of families with Birt-Hogg-Dubé syndrome. Am J Hum Genet. 2005 Jun. 76(6):1023-33. [QxMD MEDLINE Link]. [Full Text].

22. Toro JR, Wei MH, Glenn GM, et al. BHD mutations, clinical and molecular genetic investigations of Birt-Hogg-Dubé syndrome: a new series of 50 families and a review of published reports. J Med Genet. 2008 Jun. 45(6):321-31. [QxMD MEDLINE Link]. [Full Text].

23. Graham RB, Nolasco M, Peterlin B, Garcia CK. Nonsense mutations in folliculin presenting as isolated familial spontaneous pneumothorax in adults. Am J Respir Crit Care Med. 2005 Jul 1. 172(1):39-44. [QxMD MEDLINE Link].

24. Schmidt LS. Birt-Hogg-Dube syndrome, a genodermatosis that increases risk for renal carcinoma. Curr Mol Med. 2004 Dec. 4(8):877-85. [QxMD MEDLINE Link].

25. Toro JR, Pautler SE, Stewart L, et al. Lung cysts, spontaneous pneumothorax, and genetic associations in 89 families with Birt-Hogg-Dubé syndrome. Am J Respir Crit Care Med. 2007 May 15. 175(10):1044-53. [QxMD MEDLINE Link]. [Full Text].

26. Zbar B, Alvord WG, Glenn G, et al. Risk of renal and colonic neoplasms and spontaneous pneumothorax in the Birt-Hogg-Dubé syndrome. Cancer Epidemiol Biomarkers Prev. 2002 Apr. 11(4):393-400. [QxMD MEDLINE Link].

27. Spring P, Fellmann F, Giraud S, Clayton H, Hohl D. Syndrome of Birt-Hogg-Dubé, a histopathological pitfall with similarities to tuberous sclerosis: a report of three cases. Am J Dermatopathol. 2013 Apr. 35(2):241-5. [QxMD MEDLINE Link].

28. Furuya M, Nakatani Y. Birt-Hogg-Dube syndrome: clinicopathological features of the lung. J Clin Pathol. 2013 Mar. 66(3):178-86. [QxMD MEDLINE Link]. [Full Text].

29. Auerbach A, Roberts DH, Gangadharan SP, Kent MS. Birt-Hogg-Dubé syndrome in a patient presenting with familial spontaneous pneumothorax. Ann Thorac Surg. 2014 Jul. 98 (1):325-7. [QxMD MEDLINE Link].

30. Johannesma PC, van den Borne BE, Gille JJ, Nagelkerke AF, van Waesberghe JT, Paul MA, et al. Spontaneous pneumothorax as indicator for Birt-Hogg-Dubé syndrome in paediatric patients. BMC Pediatr. 2014 Jul 3. 14:171. [QxMD MEDLINE Link].

31. Torricelli E, Occhipinti M, Cavigli E, Tancredi G, Rosi E, Rossi C, et al. The Relevance of Family History Taking in the Detection and Management of Birt-Hogg-Dubé Syndrome. Respiration. 2019. 98 (2):125-132. [QxMD MEDLINE Link].

32. Daccord C, et al. Lung function in Birt-Hogg-Dubé syndrome: a retrospective analysis of 96 patients. Orphanet J Rare Dis. 2020 May 24. 15 (1):120. [QxMD MEDLINE Link].

33. Schmidt LS, Linehan WM. Molecular genetics and clinical features of Birt-Hogg-Dubé syndrome. Nat Rev Urol. 2015 Oct. 12 (10):558-69. [QxMD MEDLINE Link].

34. Liu V, Kwan T, Page EH. Parotid oncocytoma in the Birt-Hogg-Dubé syndrome. J Am Acad Dermatol. 2000 Dec. 43(6):1120-2. [QxMD MEDLINE Link].

35. Nadershahi NA, Wescott WB, Egbert B. Birt-Hogg-Dubé syndrome: a review and presentation of the first case with oral lesions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1997 Apr. 83(4):496-500. [QxMD MEDLINE Link].

36. Schaffer JV, Gohara MA, McNiff JM, Aasi SZ, Dvoretzky I. Multiple facial angiofibromas: a cutaneous manifestation of Birt-Hogg-Dubé syndrome. J Am Acad Dermatol. 2005 Aug. 53(2 Suppl 1):S108-11. [QxMD MEDLINE Link].

37. Vincent A, Farley M, Chan E, James WD. Birt-Hogg-Dubé syndrome: two patients with neural tissue tumors. J Am Acad Dermatol. 2003 Oct. 49(4):717-9. [QxMD MEDLINE Link].

38. Cocciolone RA, Crotty KA, Andrews L, Haass NK, Moloney FJ. Multiple desmoplastic melanomas in Birt-Hogg-Dubé syndrome and a proposed signaling link between folliculin, the mTOR pathway, and melanoma susceptibility. Arch Dermatol. 2010 Nov. 146(11):1316-8. [QxMD MEDLINE Link].

39. Mota-Burgos A, Acosta EH, Márquez FV, Mendiola M, Herrera-Ceballos E. Birt-Hogg-Dubé syndrome in a patient with melanoma and a novel mutation in the FCLN gene. Int J Dermatol. 2013 Mar. 52(3):323-6.

40. Lindor NM, Kasperbauer J, Lewis JE, Pittelkow M. Birt-Hogg-Dube syndrome presenting as multiple oncocytic parotid tumors. Hered Cancer Clin Pract. 2012. 10(1):13. [QxMD MEDLINE Link].

41. Renfree KJ, Lawless KL. Multiple neurilemmomas in Birt-Hogg-Dubé syndrome: case report. J Hand Surg Am. 2012 Apr. 37(4):792-4. [QxMD MEDLINE Link].

42. Sattler EC, Syunyaeva Z, Reithmair M, Dempke W, Steinlein OK. Colorectal cancer risk in families with Birt-Hogg-Dubé syndrome increased. Eur J Cancer. 2021 Jul. 151:168-174. [QxMD MEDLINE Link].

43. van de Beek I, Glykofridis IE, Wolthuis RMF, Gille HJJP, Johannesma PC, Meijers-Heijboer HEJ, et al. No evidence for increased prevalence of colorectal carcinoma in 399 Dutch patients with Birt-Hogg-Dubé syndrome. Br J Cancer. 2020 Feb. 122 (4):590-594. [QxMD MEDLINE Link].

44. Claessens T, Weppler SA, van Geel M, et al. Neuroendocrine carcinoma in a patient with Birt-Hogg-Dubé syndrome. Nat Rev Urol. 2010 Oct. 7(10):583-7. [QxMD MEDLINE Link].

45. Lim DH, Rehal PK, Nahorski MS, et al. A new locus-specific database (LSDB) for mutations in the folliculin (FLCN) gene. Hum Mutat. 2010 Jan. 31(1):E1043-51. [QxMD MEDLINE Link].

46. Kluger N, Giraud S, Coupier I, Avril MF, Dereure O, Guillot B, et al. Birt-Hogg-Dubé syndrome: clinical and genetic studies of 10 French families. Br J Dermatol. 2010 Mar. 162 (3):527-37. [QxMD MEDLINE Link].

47. European Birt-Hogg-Dube Consortium. LOVD Gene Homepage for FLCN. Leiden Open Variation Database. Available at https://grenada.lumc.nl/LOVD2/shared1/home.php?select_db=FLCN. May 13, 2016; Accessed: February 16, 2017.

48. Cai M, Zhang X, Fan L, Cheng S, Kiram A, Cen S, et al. A Novel FLCN Intragenic Deletion Identified by NGS in a BHDS Family and Literature Review. Front Genet. 2021. 12:636900. [QxMD MEDLINE Link].

49. Pradella LM, Lang M, Kurelac I, Mariani E, Guerra F, Zuntini R, et al. Where Birt-Hogg-Dubé meets Cowden syndrome: mirrored genetic defects in two cases of syndromic oncocytic tumours. Eur J Hum Genet. 2013 Oct. 21 (10):1169-72. [QxMD MEDLINE Link]. [Full Text].

50. Bessis D, Giraud S, Richard S. A novel familial germline mutation in the initiator codon of the BHD gene in a patient with Birt-Hogg-Dubé syndrome. Br J Dermatol. 2006 Nov. 155(5):1067-9. [QxMD MEDLINE Link].

51. Leter EM, Koopmans AK, Gille JJ, et al. Birt-Hogg-Dubé syndrome: clinical and genetic studies of 20 families. J Invest Dermatol. 2008 Jan. 128(1):45-9. [QxMD MEDLINE Link].

52. Kim J, Yoo JH, Kang DY, Cho NJ, Lee KA. Novel in-frame deletion mutation in FLCN gene in a Korean family with recurrent primary spontaneous pneumothorax. Gene. 2012 May 15. 499(2):339-42. [QxMD MEDLINE Link].

53. Nagashima Y, Furuya M, Gotohda H, Takagi S, Hes O, Michal M. FLCN gene-mutated renal cell neoplasms: mother and daughter cases with a novel germline mutation. Int J Urol. 2012 May. 19(5):468-70. [QxMD MEDLINE Link].

54. Wei MH, Blake PW, Shevchenko J, Toro JR. The folliculin mutation database: an online database of mutations associated with Birt-Hogg-Dubé syndrome. Hum Mutat. 2009 Sep. 30(9):E880-90. [QxMD MEDLINE Link].

55. Hasumi H, Baba M, Hasumi Y, Lang M, Huang Y, Oh HF, et al. Folliculin-interacting proteins Fnip1 and Fnip2 play critical roles in kidney tumor suppression in cooperation with Flcn. Proc Natl Acad Sci U S A. 2015 Mar 31. 112 (13):E1624-31. [QxMD MEDLINE Link].

56. Baba M, Hong SB, Sharma N, et al. Folliculin encoded by the BHD gene interacts with a binding protein, FNIP1, and AMPK, and is involved in AMPK and mTOR signaling. Proc Natl Acad Sci U S A. 2006 Oct 17. 103(42):15552-7. [QxMD MEDLINE Link]. [Full Text].

57. Tee AR, Pause A. Birt-Hogg-Dubé: tumour suppressor function and signalling dynamics central to folliculin. Fam Cancer. 2012 Oct 25.

58. Medvetz DA, Khabibullin D, Hariharan V, Ongusaha PP, Goncharova EA, Schlechter T, et al. Folliculin, the product of the Birt-Hogg-Dube tumor suppressor gene, interacts with the adherens junction protein p0071 to regulate cell-cell adhesion. PLoS One. 2012. 7(11):

59. Ramirez Reyes JMJ, Cuesta R, Pause A. Folliculin: A Regulator of Transcription Through AMPK and mTOR Signaling Pathways. Front Cell Dev Biol. 2021. 9:667311. [QxMD MEDLINE Link].

60. Nahorski MS, Reiman A, Lim DH, Nookala RK, Seabra L, Lu X, et al. Birt Hogg-Dubé syndrome-associated FLCN mutations disrupt protein stability. Hum Mutat. 2011 Aug. 32 (8):921-9. [QxMD MEDLINE Link].

61. Benhammou JN, Vocke CD, Santani A, Schmidt LS, Baba M, Seyama K, et al. Identification of intragenic deletions and duplication in the FLCN gene in Birt-Hogg-Dubé syndrome. Genes Chromosomes Cancer. 2011 Jun. 50 (6):466-77. [QxMD MEDLINE Link].

62. Koga S, Furuya M, Takahashi Y, Tanaka R, Yamaguchi A, Yasufuku K, et al. Lung cysts in Birt-Hogg-Dubé syndrome: histopathological characteristics and aberrant sequence repeats. Pathol Int. 2009 Oct. 59 (10):720-8. [QxMD MEDLINE Link].

63. Vincent A, Farley M, Chan E, James WD. Birt-Hogg-Dubé syndrome: a review of the literature and the differential diagnosis of firm facial papules. J Am Acad Dermatol. 2003 Oct. 49(4):698-705. [QxMD MEDLINE Link].

64. Ayo DS, Aughenbaugh GL, Yi ES, Hand JL, Ryu JH. Cystic lung disease in Birt-Hogg-Dube syndrome. Chest. 2007 Aug. 132(2):679-84. [QxMD MEDLINE Link].

65. Aivaz O, Berkman S, Middelton L, Linehan WM, DiGiovanna JJ, Cowen EW. Comedonal and Cystic Fibrofolliculomas in Birt-Hogg-Dube Syndrome. JAMA Dermatol. 2015 Jul. 151 (7):770-4. [QxMD MEDLINE Link].

66. Chung JY, Ramos-Caro FA, Beers B, Ford MJ, Flowers F. Multiple lipomas, angiolipomas, and parathyroid adenomas in a patient with Birt-Hogg-Dube syndrome. Int J Dermatol. 1996 May. 35(5):365-7. [QxMD MEDLINE Link].

67. Shvartsbeyn M, Mason AR, Bosenberg MW, Ko CJ. Perifollicular fibroma in Birt-Hogg-Dubé syndrome: an association revisited. J Cutan Pathol. 2012 Jul. 39(7):675-9. [QxMD MEDLINE Link].

68. Kamada T, Yoshikawa Y, Shirase T, Furuya M, Yutaka Y. Perifollicular fibromas associated with Birt-Hogg-Dubé syndrome. J Dermatol. 2015 Sep 21. [QxMD MEDLINE Link].

69. Schaffer JV, Gohara MA, McNiff JM, Aasi SZ, Dvoretzky I. Multiple facial angiofibromas: a cutaneous manifestation of Birt-Hogg-Dubé syndrome. J Am Acad Dermatol. 2005 Aug. 53 (2 Suppl 1):S108-11. [QxMD MEDLINE Link].

70. Menko FH, van Steensel MA, Giraud S, et al. Birt-Hogg-Dubé syndrome: diagnosis and management. Lancet Oncol. 2009 Dec. 10(12):1199-206. [QxMD MEDLINE Link].

71. Gupta P, Eshaghi N, Kamba TT, Ghole V, Garcia-Morales F. Radiological findings in Birt-Hogg-Dubé syndrome: a rare differential for pulmonary cysts and renal tumors. Clin Imaging. 2007 Jan-Feb. 31(1):40-3. [QxMD MEDLINE Link].

72. Collins GL, Somach S, Morgan MB. Histomorphologic and immunophenotypic analysis of fibrofolliculomas and trichodiscomas in Birt-Hogg-Dube syndrome and sporadic disease. J Cutan Pathol. 2002 Oct. 29(9):529-33. [QxMD MEDLINE Link].

73. Heenan PJ. Tumors of the fibrous tissue involving the skin. Elder D, Elenitsas R, Jaworsky C, Johnson B Jr, eds. Lever's Histopathology of the Skin. 8th ed. Lippincott Wilkins & Williams; 1997. 872-4.

74. Pinkus H, Coskey R, Burgess GH. Trichodiscoma. A benign tumor related to haarscheibe (hair disk). J Invest Dermatol. 1974 Aug. 63(2):212-8. [QxMD MEDLINE Link].

75. Lopez-Garcia DR, Teague D, Landis ET, Sangueza OP. Morphological diversity of trichodiscomas and fibrofolliculomas. Am J Dermatopathol. 2014 Sep. 36 (9):734-40. [QxMD MEDLINE Link].

76. Schulz T, Hartschuh W. Birt-Hogg-Dubé syndrome and Hornstein-Knickenberg syndrome are the same. Different sectioning technique as the cause of different histology. J Cutan Pathol. 1999 Jan. 26(1):55-61. [QxMD MEDLINE Link].

77. Gijezen LM, Vernooij M, Martens H, Oduber CE, Henquet CJ, Starink TM, et al. Topical rapamycin as a treatment for fibrofolliculomas in Birt-Hogg-Dubé syndrome: a double-blind placebo-controlled randomized split-face trial. PLoS One. 2014. 9 (6):e99071. [QxMD MEDLINE Link].

78. Pritchard SE, Mahmoudizad R, Parekh PK. Successful treatment of facial papules with electrodessication in a patient with Birt-Hogg-Dubé syndrome. Dermatol Online J. 2014 Jul 15. 20 (7):[QxMD MEDLINE Link].

79. Gambichler T, Wolter M, Altmeyer P, Hoffman K. Treatment of Birt-Hogg-Dubé syndrome with erbium:YAG laser. J Am Acad Dermatol. 2000 Nov. 43(5 Pt 1):856-8. [QxMD MEDLINE Link].

80. Jacob CI, Dover JS. Birt-Hogg-Dube syndrome: treatment of cutaneous manifestations with laser skin resurfacing. Arch Dermatol. 2001 Jan. 137(1):98-9. [QxMD MEDLINE Link].

81. Vazirnia A, Schneider J, Ortiz A. Treatment of Benign Adnexal Tumors in Birt-Hogg-Dubé Syndrome With Surgical Debulking in Combination With Fractional and Fully Ablative Carbon Dioxide Laser Resurfacing. Dermatol Surg. 2020 Nov. 46 (11):1464-1465. [QxMD MEDLINE Link].

Michelle Bongiorno Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine

Michelle Bongiorno is a member of the following medical societies: American Medical Association

Disclosure: Nothing to disclose.

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Franklin Flowers, MD Professor Emeritus, Department of Dermatology, Affiliate Associate Professor of Pathology, University of Florida College of Medicine

Franklin Flowers, MD is a member of the following medical societies: American College of Mohs Surgery

Disclosure: Nothing to disclose.

Jeffrey Meffert, MD † Former Associate Clinical Professor of Dermatology, University of Texas School of Medicine at San Antonio

Jeffrey Meffert, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Krista K Buckley, DO Dermatologist, Annapolis Dermatology Center

Krista K Buckley, DO is a member of the following medical societies: American Academy of Dermatology, Maryland Dermatologic Society

Disclosure: Nothing to disclose.

Mary Farley, MD Dermatologic Surgeon/Mohs Surgeon, Anne Arundel Surgery Center

Disclosure: Nothing to disclose.

• Print this section
• Print the entire contents of
• Print the entire contents of article