Birt–Hogg–Dubé syndrome

894: 335: 229: 220: 433:. Spontaneous, sometimes recurrent, pneumothorax occurs far more often and at a younger age with BHD than in the unaffected population. Around 24% of people with the disease have at least one spontaneous pneumothorax, 30 times the occurrence in unaffected people. Though pneumothorax caused by BHD often occurs in middle age, at a median age of 38, 17% of affected people have a spontaneous pneumothorax before turning 40. Pneumothoraces have been seen in people as young as 7 and 16 years of age. Some families have a form of BHD that only affects the lungs. 45: 69: 555: 362:, and possibly tumors in other organs and tissues. These tumors often occur in both kidneys and in multiple locations in each kidney. The average number of kidney tumors found in a person with BHD is 5.3, though up to 28 tumors have been found. Hybrid oncocytoma/chromophobe carcinoma, found in 50% of cases, is the most commonly found cancer, followed by chromophobe renal carcinoma, clear cell renal carcinoma, renal oncocytoma, and 744: 590:-rich region in exon 11 particularly susceptible to mutation. The most common mutation in this region is the insertion or deletion of a cytosine residue, found in 53% of BHD-affected families. No significant difference has been found in the symptoms experienced by families with an insertion at that location compared to those who have a deletion, but mutations in 136:. The symptoms seen in each family are unique, and can include any combination of the three symptoms. Fibrofolliculomas are the most common manifestation, found on the face and upper trunk in over 80% of people with BHD over the age of 40. Pulmonary cysts are equally common (84%) and 24% of people with BHD eventually experience a collapsed lung ( 378:. If it develops in someone with BHD, renal cell carcinoma occurs later in life and has a poor prognosis. Though the types of tumors typically associated with BHD are considered less aggressive, cases of advanced or metastatic kidney cancer have been observed in people with the syndrome. Both benign and cancerous tumors can reduce 856:, and oncocytic hybrid tumors) are more commonly seen. Although the original syndrome was discovered on the basis of cutaneous findings, individuals with BHD may only manifest the pulmonary and/or renal findings, without any skin lesions. Though these signs indicate BHD, it is only confirmed with a genetic test for 1077:

father, all of whom exhibited colon polyps and the characteristic fibrofolliculomas. Though the siblings did not have renal or pulmonary symptoms, their father had cysts in his lungs and kidneys. Hornstein-Knickenberg syndrome is a now-deprecated name for the inherited fibrofolliculomas inherent to BHD.

2277:

Nickerson, Michael L.; Warren, Michelle B.; Toro, Jorge R.; Matrosova, Vera; Glenn, Gladys; Turner, Maria L.; Duray, Paul; Merino, Maria; Choyke, Peter; et al. (2002), "Mutations in a novel gene lead to kidney tumors, lung wall defects, and benign tumors of the hair follicle in patients with the

1158:

homolog that produces a truncated protein, though they do not develop the cutaneous or pulmonary symptoms seen in humans. Heterozygotes have renal abnormalities seen very early in life that develop into clear-cell and hybrid tumors, significantly shortening the animals' lifespans; they also are prone

1080:

Birt, Hogg, and Dubé examined a family with a hereditary thyroid cancer, and discovered that many of the members had fibrofolliculomas, trichodiscomas, and acrochordons, which became defined as the classical symptoms of the eponymous disease. The first case of spontaneous pneumothorax associated with

1046:

The disorder has been reported in more than 100 families worldwide, though some sources cite up to 400 families, and it is inherited in an autosomal dominant pattern. It is considered to be under-diagnosed because of the variability in its expression. The pattern of mutations and spectrum of symptoms

771:

gene—is enough to cause the fibrofolliculomas and pulmonary cysts, though one copy of the gene is enough to keep kidney cells in check. During a person's lifetime, random mutations might inactivate the normal copy of the gene in a subset of cells. When this occurs, the result is that these cells have

444:

have been associated with the Birt–Hogg–Dubé phenotype, present in 65% of individuals and 90% of families with the syndrome. However, a connection between BHD and thyroid cancer has not been substantiated. Other conditions have been reported to be associated, but may not be caused by the mutation in

1076:

on a 56-year-old woman's face. Trichodiscomas were first described in 1974 by H. S. Zackheim and H. Pinkus, but were not associated with BHD until Birt, Hogg, and Dubé. The first case of BHD with the systemic symptoms was described by Hornstein and Knickenberg and found in two siblings and their

839:

The cutaneous manifestations of BHD were originally described as fibrofolliculomas (abnormal growths of a hair follicle), trichodiscomas (hamartomatous lesions with a hair follicle at the periphery, often found on the face), and acrochordons (skin tags). Cutaneous manifestations are confirmed by

614:, which means that they occur in every cell of the body and can be passed down to future generations. These mutations are often passed from one generation to the next in an autosomal dominant fashion, but can occur as a new mutation in an individual with no prior family history (a 879:

with this syndrome. This means that some people with the clinical diagnosis have mutations that are not detectable by current technology, or that mutations in another currently unknown gene could be responsible for a minority of cases. In addition, amplifications and deletions in

2431:

Toro, J R; Wei, M-H; Glenn, G M; Weinreich, M; Toure, O; Vocke, C; Turner, M; Choyke, P; Merino, M J; et al. (2008), "BHD mutations, clinical and molecular genetic investigations of Birt-Hogg-Dube syndrome: A new series of 50 families and a review of published reports",

2227:

Menko, Fred H; Van Steensel, Maurice AM; Giraud, Sophie; Friis-Hansen, Lennart; Richard, Stéphane; Ungari, Silvana; Nordenskjöld, Magnus; Hansen, Thomas vO; Solly, John; Maher, Eamonn R; European Bhd, Consortium (2009), "Birt-Hogg-Dubé syndrome: Diagnosis and management",

251:), particularly on the face, neck, and more rarely, the upper chest. The fibrofolliculomas are generally described as having an opaque white color or a yellowish tone and have a waxy, smooth texture. The tumors are always found on and around the nose and on and behind the 1184:

have been created for a kidney-cancer causing mutation of BHD; heterozygotes develop kidney cysts and tumors that lead to renal failure within three weeks of birth. In these mice, the mTOR pathway was inappropriately activated, indicating that the mouse homolog of

1806:

Singh SR, Zhen W, Zheng Z, Wang H, Oh SW, Liu W, Zbar B, Schmidt LS, Hou SX. The Drosophila homolog of the human tumor suppressor gene BHD interacts with the JAK-STAT and Dpp signaling pathways in regulating male germline stem cell maintenance. Oncogene. 2006 Sep

1796:

1071:

The syndrome was first well described in 1977, by three Canadian physicians, Arthur R. Birt, Georgina R. Hogg, and William J. Dubé. The earliest case of possible BHD in the medical literature was published by Burnier and Rejsek in 1927, who described a case of

2372:

Sudarshan, Sunil; Karam, Jose A.; Brugarolas, James; Thompson, R. Houston; Uzzo, Robert; Rini, Brian; Margulis, Vitaly; Patard, Jean-Jacques; Escudier, Bernard; Linehan, W. Marston (2013), "Metabolism of Kidney Cancer: From the Lab to Clinical Practice",

255:. Typically, they first appear in a person's 20s or 30s, and are found in more than 80% of people with the syndrome above the age of 40. The tumors become larger and more numerous over time. Tumors differ between individuals; they may appear merged in 1623:

Napolitano G, Di Malta C, Esposito A, de Araujo ME, Pece S, Bertalot G, Matarese M, Benedetti V, Zampelli A, Stasyk T, Siciliano D, Venuta A, Cesana M, Vilardo C, Nusco E, Monfregola J, Calcagnì A, Di Fiore PP, Huber LA, Ballabio A (September 2020).

905:

BHD can be difficult to diagnose from symptoms alone, because hereditary renal cancers, pneumothorax, and cutaneous tumors occur with other syndromes. Hereditary bilateral, multifocal kidney tumors similar to those seen in BHD can occur with

369:

In general, people with this syndrome are at roughly at seven times the risk of kidney cancer compared to the unaffected population. Estimates of the incidence among people with the disease range from 14 to 34%. Rarely, it is associated with

719:

Most of the cancer-causing mutations cause the protein to be truncated at the carboxy terminus. The C-terminal end of folliculin has shown to be the domain through which it interacts with FNIP1, and thereby possibly the mTOR pathway.

956:

Though fibrofolliculomas are unique to BHD, they may present with an ambiguous appearance and must be confirmed histologically. Other diseases can mimic the dermatologic manifestations of BHD, including tuberous sclerosis complex,

198:. Fibrofolliculomas can be removed surgically and pneumothorax and kidney cancer are treated according to the normal standard of care. Dermatologic examinations, neck ultrasounds and colonoscopies should be considered as well 805:

has been found to be overexpressed in fibrofolliculoma tissue, and to have very low levels of expression in affected kidneys. Furthermore, the mTOR pathway is shown to be activated in tumor tissue from both humans and mice.

780:

is a common mechanism in cancer, and it is frequently detected in the renal cancers associated with BHD. The molecular genetic defects in renal tumors of people with BHD are different from two other similar kidney tumors,

570:) and the affected parent produces half mutant gametes and half normal gametes. Because only one copy of the mutation is needed to have an autosomal dominant disease, each offspring has a 50% chance of having the mutation. 2470:

Verine, Jérôme; Pluvinage, Amélie; Bousquet, Guilhem; Lehmann-Che, Jacqueline; De Bazelaire, Cédric; Soufir, Nadem; Mongiat-Artus, Pierre (2010), "Hereditary Renal Cancer Syndromes: An Update of a Systematic Review",

884:

regions are also tested. Genetic testing can be useful to confirm the clinical diagnosis and to provide a means of determining other at-risk individuals in a family even if they have not yet developed BHD symptoms.

298:. However, angiofibromas are more common in tuberous sclerosis. Along with the tumors, other skin conditions are seen in people with Birt–Hogg–Dubé syndrome. About 40% of people or families with the disease have 1013:

of the kidneys are recommended regularly, and family members are advised not to smoke. MRIs are the preferred method for surveillance of the kidneys in people with BHD because they do not carry the same risk of

1150:

regulates GSC maintenance downstream or in parallel of the JAK/STAT and Dpp signal-transduction pathways, which suggest that BHD regulates tumorigenesis by controlling stem cells in human { Singh et al. 2006}

1081:

BHD was discovered in 1986; the first case of renal cancer followed in 1993, and the presence of lung cysts in people with BHD was confirmed in 1999. People with BHD were once thought to be at higher risk for

366:. People over 40 years old and men are more likely to develop kidney tumors, which are diagnosed at a median age of 48. Kidney cancer associated with BHD have been diagnosed in people at ages as young as 20. 834: 949:. These conditions are differentiated from BHD through examining the patient history and performing a physical examination. In women suspected to have the disease, ruling out pulmonary or thoracic 1089:, but this has been disproven. The BHD Foundation supports research into the syndrome and holds regular symposia in BHD and related disorders for researchers, clinicians, and family members. 915: 1063:. This is a privacy-protected site that provides up-to-date information for individuals interested in the latest scientific news, trials, and treatments related to rare lung diseases. 243:

Birt–Hogg–Dubé syndrome affects the skin and increases the risk of tumors in the kidneys and lungs. The condition is characterized by multiple noncancerous, dome-shaped tumors of the

2143:

Liu, Wei; Chen, Zhi; Ma, Yansen; Wu, Xiaochun; Jin, Yaping; Hou, Steven (2013), White-Cooper, Helen (ed.), "Genetic Characterization of the Drosophila Birt-Hogg-Dubé Syndrome Gene",

2308:

Palmirotta, Raffaele; Savonarola, Annalisa; Ludovici, Giorgia; Donati, Pietro; Cavaliere, Francesco; De Marchis, Maria Laura; Ferroni, Patrizia; Guadagni, Fiorella (March 2010),

901:. The skin lesions caused by tuberous sclerosis (angiofibromas) must be distinguished from the characteristic fibrofolliculomas of BHD, which also occur primarily on the face. 326:, and in folds of skin. Not all individuals develop the facial tumors; some families with the mutation that causes BHD develop only kidney tumors or spontaneous pneumothorax. 2630: 1146:. Decrease expression of the DBHD results in loss of male germline stem cells (GSC), which suggest that DBHD is required for male GSC maintenance in the fly testis. Further, 844:. Most individuals (89%) with BHD are found to have multiple cysts in both lungs, and 24% have had one or more episodes of pneumothorax. The cysts can be detected by chest 825:

gene. The classical clinical triad includes benign growths of the hair follicles, pulmonary cysts and spontaneous pneumothorax, and bilateral, multifocal renal tumors.

2073:

Grant, L.A.; Babar, J.; Griffin, N. (2009), "Cysts, cavities, and honeycombing in multisystem disorders: Differential diagnosis and findings on thin-section CT",

2050: 2256: 969:. Tuberous sclerosis must be distinguished because both disorders can present with angiofibromas on the face, though they are more common in tuberous sclerosis. 3053: 1018:

complications as CT scans, and are more sensitive than ultrasounds. Smokers with Birt–Hogg–Dubé have more severe pulmonary symptoms than non-smokers. Though

934: 712:. Folliculin's participation in the mTOR pathway may explain the similarity in phenotype between BHD syndrome, Cowden syndrome, tuberous sclerosis, and 1060: 736:, is affected by a missense mutation in some people with BHD. The lysine at this position is found to be conserved between invertebrate and vertebrate 2623: 306:), tongue, gums, or lips. Either white or mucosa-colored, they are discrete, small, and soft, and consist of fibrous tissue covered in thickened 194:, which causes hereditary kidney cancers. Once diagnosed, people with BHD are treated preventatively, with monitoring of kidneys and lungs using 3068: 3058: 3008: 2110: 422: 140:). Kidney tumors, both cancerous and benign, occur in 14–34% of people with BHD; the associated kidney cancers are often rare hybrid tumors. 1101:

and diseases similar to BHD have been found in dogs, fruit flies, rats, and mice. In German Shepherd dogs, missense mutations in the canine

893: 3003: 2885: 2522: 966: 962: 2616: 143:

Any of these conditions that occurs in a family can indicate a diagnosis of Birt–Hogg–Dubé syndrome, though it is only confirmed by a

2415:, in Pagon, Roberta A; Adam, Margaret P; Bird, Thomas D; Dolan, Cynthia R; Fong, Chin-To; Smith, Richard JH; Stephens, Karen (eds.), 1051:

between individuals. Less severe skin phenotypes are seen in women and people of both sexes who have a late onset of skin symptoms.

911: 2965: 2937: 186:

Birt–Hogg–Dubé syndrome can manifest similarly to other diseases, which must be ruled out when making a diagnosis. These include

183:

was not elucidated until 2002, after kidney cancer, collapsed lungs, and pulmonary cysts were all definitively connected to BHD.

2332:

Reese, Erin; Sluzevich, Jason; Kluijt, Irma; Teertstra, H. Jelle; De Jong, Daphne; Horenblas, Simon; Ryu, Jay (5 October 2009),

2932: 2732: 977:

The different manifestations of BHD are controlled in different ways. The fibrofolliculomas can be removed surgically, through

526: 371: 1878: 3063: 2895: 676:. Tumor suppressors normally prevent cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in the 907: 421:

is usually normal. More than 83% of people with BHD have cysts, but the syndrome does not cause conditions like progressive

334: 191: 2998: 2900: 2262: 942: 709: 1189:

plays a regulatory role in this pathway. Rapamycin partially rescued the phenotype by regulating mTOR. Homozygotes die

2058: 1850:

Birt, A. R.; Hogg, GR; Dubé, WJ (1977), "Hereditary multiple fibrofolliculomas with trichodiscomas and acrochordons",

558:

This diagram shows how autosomal dominant disorders like BHD are passed on. The unaffected parent produces all normal

454: 351: 228: 219: 1822:

Ayo, Dereje S.; Aughenbaugh, GL; Yi, ES; Hand, JL; Ryu, JH (2007), "Cystic Lung Disease in Birt-Hogg-Dubé Syndrome",

926: 713: 684:

and cancerous tumors. Recent studies suggest that folliculin accomplishes this function through its involvement with

848:. Renal tumors can manifest as multiple types of renal cell carcinoma, but certain pathological subtypes (including 680:

gene may interfere with the ability of folliculin to restrain cell growth and division, leading to the formation of

44: 2890: 2353: 1038:

mutations on kidneys and improve renal cancer prognoses because of folliculin's interaction with the mTOR pathway.

930: 2677: 1154:

A line of rats with hereditary kidney cancer were developed by Japanese researchers. They have a mutation in the

809:

Renal cystogenesis and tumorigenesis in BHD have been shown to be driven by the constitutive activation of TFEB.

697: 502: 3030: 2835: 2747: 2533: 1571: 946: 482: 137: 2815: 2120: 1117:). They had a similar pattern of tumorigenesis to human BHD in that the skin lesions were heterozygous for the 1022:

is sometimes indicated, kidney tumors in cases of BHD are often removed without taking the whole kidney, in a

1114: 3073: 2875: 1167: 1142: 1121:

mutation, and the renal tumors were likely caused by loss of heterozygosity. Female German Shepherds with a

538: 466: 164: 2975: 2927: 1073: 777: 295: 276: 2840: 2737: 2702: 2309: 1993:

Furuya, M.; Nakatani, Y. (2012), "Birt-Hogg-Dube syndrome: Clinicopathological features of the lung",

314:

of the skin are also found in some families. Many people with BHD have skin lesions that appear to be

2766: 2712: 2152: 1637: 621:). The children of an affected parent each has a 50% chance of having the disease. BHD has very high 530: 375: 363: 342:

of tissue from a chromophobe renal cell carcinoma, the second-most common cancer associated with BHD

68: 2820: 2762: 2692: 2669: 1023: 845: 685: 599: 478: 450: 426: 399: 256: 2603: 271:. A large number of tumors on the face can be associated with hyperseborrhea (abnormally elevated 2788: 2783: 2216: 1671: 1110: 898: 764: 725: 187: 98: 2947: 2880: 2825: 2725: 2682: 2544: 2488: 2459: 2420: 2400: 2341: 2336:, in Riegert-Johnson, Douglas L; Boardman, Lisa A; Hefferon, Timothy; Roberts, Maegan (eds.), 2321: 2297: 2245: 2208: 2180: 2106: 2090: 2020: 1982: 1944: 1916: 1867: 1839: 1663: 1126: 1082: 986: 653: 611: 607: 595: 514: 57: 2970: 2917: 2480: 2449: 2441: 2390: 2382: 2287: 2237: 2200: 2170: 2160: 2082: 2010: 2002: 1972: 1964: 1936: 1908: 1859: 1831: 1653: 1645: 645: 615: 603: 510: 462: 355: 248: 237:

Individual with Birt–Hogg–Dubé syndrome, showing the characteristic facial fibrofolliculomas

156: 133: 101: 62: 2031: 1955:

Devine, Megan Stuebner; Garcia, Christine Kim (2012), "Genetic Interstitial Lung Disease",

417:), which could result in the collapse of a lung. The cysts do not cause other symptoms and 2810: 2802: 958: 938: 922: 818: 705: 441: 395: 379: 318:(skin tags), but may instead be fibrofolliculomas. These lesions are usually found in the 268: 252: 195: 168: 2156: 1641: 554: 390:

Along with fibrofolliculomas and kidney tumors, affected individuals frequently develop

275:

production). The presence of fibrofolliculomas on a person's face can cause significant

52:

The characteristic fibrofolliculomas of Birt–Hogg–Dubé syndrome seen on a person's face.

3022: 2912: 2752: 2643: 2454: 2395: 2175: 2015: 1977: 1658: 1625: 1171: 1164: 1027: 990: 534: 498: 346:

People over 20 years of age with BHD have an increased risk of developing slow-growing

121: 17: 2292: 2241: 1884: 1109:

cause a similar phenotype to human BHD—kidney cancers (in this case, multifocal renal

1059:

Birt-Hogg-Dubé Syndrome patients, families, and caregivers are encouraged to join the

3047: 2942: 2922: 2907: 2871: 2687: 1675: 1181: 1048: 950: 817:

BHD can be suggested by clinical findings but is definitively diagnosed by molecular

790: 657: 583: 486: 418: 303: 283: 244: 129: 113: 2220: 610:

are observed. The mutations in the FLCN gene that cause Birt–Hogg–Dubé syndrome are

2952: 2742: 2608: 2573: 701: 681: 494: 414: 291: 144: 125: 2006: 1927:

Coleman, Jonathan A; Russo, Paul (2009), "Hereditary and familial kidney cancer",

1430: 1428: 1426: 1424: 1422: 1420: 1418: 1416: 339: 2538: 2484: 2386: 2165: 1940: 1912: 1863: 1414: 1412: 1410: 1408: 1406: 1404: 1402: 1400: 1398: 1396: 704:. Folliculin interacts with FNIP1 and FNIP2 (FLCN-interacting protein) to form a 2779: 2697: 2660: 2579: 1322: 1320: 1318: 1316: 1314: 1312: 1160: 1019: 1006: 982: 849: 782: 474: 315: 311: 2549: 2333: 2086: 2720: 2584: 2412: 1968: 1649: 1002: 998: 994: 872: 853: 786: 729: 622: 490: 458: 413:

that may rupture and cause an abnormal collection of air in the chest cavity (

410: 359: 307: 199: 152: 117: 105: 941:. Nonhereditary recurrent pneumothorax and/or pulmonary cysts can occur with 728:

in vertebrates—it is very similar between many vertebrate species. The 508th

2990: 2845: 2830: 2774: 2568: 2445: 1299: 1297: 1295: 1293: 1291: 1289: 1031: 1015: 978: 841: 693: 506: 430: 287: 2492: 2463: 2424: 2404: 2345: 2325: 2301: 2249: 2212: 2184: 2094: 2024: 1986: 1948: 1920: 1843: 1667: 1287: 1285: 1283: 1281: 1279: 1277: 1275: 1273: 1271: 1269: 743: 1835: 1772: 740:

of folliculin, indicating that it is important to the protein's function.

1871: 1102: 1086: 1005:. The renal and pulmonary symptoms are managed preventatively: CT scans, 921:

Hereditary recurrent pneumothorax or pulmonary cysts are associated with

737: 669: 665: 587: 567: 522: 2514: 2310:"Association between Birt Hogg Dubé syndrome and cancer predisposition" 1626:"A substrate-specific mTORC1 pathway underlies Birt–Hogg–Dubé syndrome" 993:; this is not a permanent solution, though, as the tumors often recur. 876: 649: 641: 518: 299: 264: 2204: 2639: 918:. They are differentiated with examination of the tumors' histology. 733: 661: 559: 470: 403: 347: 323: 319: 260: 1760: 1554: 1552: 1550: 1548: 1546: 1434: 2651: 1326: 892: 752: 742: 673: 563: 553: 333: 272: 176: 155:. Though its function is not fully understood, it appears to be a 1215: 1213: 1211: 2859: 2527: 2261:, National Organization for Rare Disorders, 2013, archived from 881: 689: 579: 406: 391: 2612: 2340:, Bethesda, MD: National Center for Biotechnology Information, 2191:

Maher, Eamonn R. (2011), "Genetics of Familial Renal Cancers",

2128: 797:

heterozygosity is responsible for cancers, and the skin, where

1010: 835:

List of cutaneous neoplasms associated with systemic syndromes

594:

associated with BHD syndrome are heterogeneous, and are often

190:, which causes skin lesions similar to fibrofolliculomas, and 179:. The disease was discovered in 1977, but the connection with 172: 2598: 1899:

Chan-Smutko, Gayun (2012), "Genetic Testing by Cancer Site",

1470: 1468: 1466: 1464: 1462: 1460: 1458: 1303: 1485: 1483: 1445: 1443: 999:. Thyroid/parotid ultrasound should be considered annually 602:

that cause early truncation of the protein product at the

159:

gene that restricts cell growth and division. Versions of

2101:

James, William D.; Berger, Timothy; Elston, Dirk (2011),

1174:. Homozygotes do not survive to birth. When a wild-type 916:

hereditary leiomyomatosis and renal cell cancer syndrome

1256: 1254: 1252: 1250: 1248: 759:

People with BHD are born with one mutated copy of the

95:

fibrofolliculomas with trichodiscomas and acrochordons

1558: 1246: 1244: 1242: 1240: 1238: 1236: 1234: 1232: 1230: 1228: 302:

in their mouths, which can be located on the cheeks (

2504: 1688: 1594: 1592: 3021: 2989: 2858: 2801: 2761: 2711: 2668: 2659: 2650: 2559: 2508: 2103:

Andrew's Diseases of the Skin: Clinical Dermatology

1383: 1381: 1379: 1377: 1375: 1373: 1371: 1369: 1367: 1365: 1363: 1361: 1359: 1357: 1355: 1219: 776:gene, allowing the cells grow out of control. This 56: 37: 1353: 1351: 1349: 1347: 1345: 1343: 1341: 1339: 1337: 1335: 1061:NIH Rare Lung Diseases Consortium Contact Registry 629:genotypes and phenotypes has not been discovered. 1501: 2051:"Birt-Hogg-Dubé syndrome: Educational resources" 1610: 1537: 648:, and is expressed strongly in the skin, distal 290:, which may be identical to fibrofolliculomas), 2038:, US National Library of Medicine, January 2013 1773:Genetics Home Reference: Educational Resources 1489: 2624: 1700: 1140:has been discovered in the common fruit fly, 8: 1712: 1525: 1513: 1474: 640:creates a protein, folliculin, that has two 449:or may not be related at all. These include 163:have been found in other animals, including 2105:(11th ed.), Elsevier Health Sciences, 1724: 1449: 1178:gene was added, the phenotype was rescued. 578:) gene was first reported in 2002. This 14- 2864: 2665: 2656: 2631: 2617: 2609: 2505: 2127:, Johns Hopkins University, archived from 1784: 1748: 1030:studies have shown that administration of 995:Dermatologic examination every 6-12 months 793:differs between the kidney, where loss of 67: 43: 34: 2453: 2394: 2291: 2174: 2164: 2014: 1976: 1657: 1572:"Rare Lung Diseases Disorder Definitions" 2119:Kniffin, Cassandra L. (22 August 2012), 1761:National Organization for Rare Disorders 801:is strongly expressed in heterozygotes. 767:—only having one functional copy of the 1736: 1260: 1207: 112:) gene. It can cause susceptibility to 27:Rare autosomal dominant cancer syndrome 914:(papillary renal cell carcinoma), and 3009:Folliculosebaceous-apocrine hamartoma 1598: 688:, possibly through modulation of the 423:chronic obstructive pulmonary disease 7: 3054:Epidermal nevi, neoplasms, and cysts 1387: 582:gene is located on the short arm of 574:An association with the folliculin ( 3004:Folliculosebaceous cystic hamartoma 2886:Multiple familial trichoepithelioma 2604:Cancer.Net: Birt-Hogg-Dubé Syndrome 2411:Toro, Jorge R. (9 September 2008), 2125:Online Mendelian Inheritance in Man 2057:, NIH, 22 July 2013, archived from 967:multiple endocrine neoplasia type 1 910:(clear cell renal cell carcinoma), 1003:Colonoscopies should be considered 625:. A correlation between different 151:gene, which codes for the protein 25: 912:hereditary papillary renal cancer 87:Hornstein–Birt–Hogg–Dubé syndrome 2966:Tumor of follicular infundibulum 2938:Giant solitary trichoepithelioma 656:. It has also been found in the 227: 218: 2933:Proliferating trichilemmal cyst 2733:Syringocystadenoma papilliferum 2193:Nephron Experimental Nephrology 1502:Grant, Babar & Griffin 2009 785:renal cell carcinoma and renal 527:dermatofibrosarcoma protuberans 382:over time as they grow larger. 372:clear cell renal cell carcinoma 2896:Desmoplastic trichoepithelioma 2121:"Birt-Hogg-Dube syndrome, BHD" 376:papillary renal cell carcinoma 364:papillary renal cell carcinoma 91:Hornstein–Knickenberg syndrome 1: 2999:Basaloid follicular hamartoma 2901:Generalized trichoepithelioma 2293:10.1016/S1535-6108(02)00104-6 2242:10.1016/S1470-2045(09)70188-3 2007:10.1136/jclinpath-2012-201200 1995:Journal of Clinical Pathology 943:Langerhans cell histiocytosis 935:alpha1-antitrypsin deficiency 897:The person in this image has 747:Folliculin is encoded by the 3069:Syndromes affecting the lung 3059:Autosomal dominant disorders 2485:10.1016/j.eururo.2010.08.031 2419:, University of Washington, 2387:10.1016/j.eururo.2012.09.054 2166:10.1371/journal.pone.0065869 1941:10.1097/MOU.0b013e32832f0d40 1913:10.1097/PPO.0b013e31826246ac 1864:10.1001/archderm.113.12.1674 1576:www1.rarediseasesnetwork.org 1034:may mitigate the effects of 772:no functional copies of the 710:AMP-activated protein kinase 104:caused by a mutation in the 2434:Journal of Medical Genetics 1125:mutation are also prone to 963:familial trichoepitheliomas 821:to detect mutations in the 455:medullary thyroid carcinoma 352:chromophobe renal carcinoma 3090: 2891:Solitary trichoepithelioma 2780:Hidradenoma or Acrospiroma 2278:Birt-Hogg-Dubé syndrome", 2087:10.1016/j.crad.2008.09.015 1929:Current Opinion in Urology 1713:Birt, Hogg & Dubé 1977 1490:Furuya & Nakatani 2012 931:tuberous sclerosis complex 871:mutations are detected by 832: 2961: 2867: 2678:Papillary eccrine adenoma 2413:"Birt-Hogg-Dubé Syndrome" 2358:Familial Cancer Syndromes 2334:"Birt-Hogg-Dubé Syndrome" 2032:"Birt-Hogg-Dubé syndrome" 1969:10.1016/j.ccm.2011.11.001 1957:Clinics in Chest Medicine 1650:10.1038/s41586-020-2444-0 908:von Hippel–Lindau disease 698:oxidative phosphorylation 644:. It appears to act as a 521:of the leg, lung cancer, 503:cutaneous focal mucinosis 483:flecked chorioretinopathy 282:Other tumors can include 192:Von Hippel–Lindau disease 97:is a human, adult onset, 51: 42: 3031:Neoplasms of the nailbed 2836:Sebaceous nevus syndrome 2748:Apocrine gland carcinoma 1526:Coleman & Russo 2009 1514:Devine & Garcia 2012 1475:Coleman & Russo 2009 997:due to risk of melanoma 947:lymphangioleiomyomatosis 535:cutaneous leiomyosarcoma 138:spontaneous pneumothorax 2981:Birt–Hogg–Dubé syndrome 2876:Malignant pilomatricoma 2585:Birt-Hogg-Dubé Syndrome 2446:10.1136/jmg.2007.054304 2055:Genetics Home Reference 2036:Genetics Home Reference 1852:Archives of Dermatology 1220:Genetics Home Reference 1143:Drosophila melanogaster 1115:nodular dermatofibrosis 1074:perifollicular fibromas 755:of human chromosome 17. 539:squamous cell carcinoma 467:connective tissue nevus 429:, though it does cause 296:perifollicular fibromas 79:Birt–Hogg–Dubé syndrome 38:Birt–Hogg–Dubé syndrome 18:Birt–Hogg–Dube syndrome 2976:Perifollicular fibroma 2928:Trichilemmal carcinoma 1883:, 2013, archived from 1327:Palmirotta et al. 2010 1168:clear-cell hyperplasia 927:Ehlers–Danlos syndrome 902: 889:Differential diagnosis 778:loss of heterozygosity 756: 714:Peutz–Jeghers syndrome 571: 411:intraparenchymal space 343: 277:psychological distress 147:for a mutation in the 3064:Syndromes with tumors 2841:Sebaceous hyperplasia 2738:Papillary hidradenoma 2703:Malignant acrospiroma 2644:associated structures 2352:Riegert-Johnson, DL, 1836:10.1378/chest.07-0042 1611:Sudarshan et al. 2013 1538:Nickerson et al. 2002 896: 751:gene, located on the 746: 692:(mammalian target of 557: 337: 600:frameshift mutations 586:(17p11.2) and has a 531:basal cell carcinoma 479:parathyroid adenomas 259:, look similar to a 2821:Sebaceous carcinoma 2816:Muir–Torre syndrome 2693:Syringofibroadenoma 2230:The Lancet Oncology 2157:2013PLoSO...865869L 1642:2020Natur.585..597N 1113:) and skin tumors ( 1024:partial nephrectomy 763:gene in each cell. 686:cellular metabolism 507:cutaneous leiomyoma 451:multinodular goiter 427:respiratory failure 126:noncancerous tumors 2789:Ceruminous adenoma 2784:Hidradenocarcinoma 2560:External resources 2265:on 3 November 2013 2075:Clinical Radiology 1901:The Cancer Journal 1797:28;25(44):5933-41. 1701:Verine et al. 2010 1127:uterine leiomyomas 1111:cystadenocarcinoma 953:may be necessary. 903: 899:tuberous sclerosis 765:Haploinsufficiency 757: 654:type I pneumocytes 612:germline mutations 608:missense mutations 596:nonsense mutations 572: 459:parotid oncocytoma 344: 205:Signs and symptoms 188:tuberous sclerosis 99:autosomal dominant 3039: 3038: 3017: 3016: 2948:Trichofolliculoma 2881:Trichoepithelioma 2854: 2853: 2826:Sebaceous adenoma 2797: 2796: 2726:Dermal cylindroma 2683:Eccrine carcinoma 2594: 2593: 2205:10.1159/000320892 2112:978-1-4377-3619-9 1807:28;25(44):5933-41 1636:(7826): 597–602. 1435:Menko et al. 2009 1304:Reese et al. 2009 1097:Genes related to 1083:colorectal polyps 789:. BHD-associated 696:) pathway and/or 515:colorectal cancer 509:, breast cancer, 463:colonic polyposis 249:fibrofolliculomas 134:fibrofolliculomas 76: 75: 32:Medical condition 16:(Redirected from 3081: 2971:Fibrofolliculoma 2918:Fibrofolliculoma 2865: 2666: 2657: 2633: 2626: 2619: 2610: 2506: 2495: 2473:European Urology 2466: 2457: 2427: 2407: 2398: 2375:European Urology 2368: 2367: 2365: 2354:"Birt-Hogg-Dube" 2348: 2338:Cancer Syndromes 2328: 2304: 2295: 2273: 2272: 2270: 2252: 2236:(12): 1199–206, 2223: 2187: 2178: 2168: 2139: 2138: 2136: 2131:on 10 March 2017 2115: 2097: 2069: 2068: 2066: 2061:on 15 March 2016 2046: 2045: 2043: 2027: 2018: 1989: 1980: 1951: 1923: 1895: 1894: 1892: 1874: 1846: 1808: 1804: 1798: 1794: 1788: 1782: 1776: 1770: 1764: 1758: 1752: 1746: 1740: 1734: 1728: 1722: 1716: 1710: 1704: 1698: 1692: 1686: 1680: 1679: 1661: 1620: 1614: 1608: 1602: 1596: 1587: 1586: 1584: 1582: 1568: 1562: 1559:Toro et al. 2008 1556: 1541: 1535: 1529: 1523: 1517: 1511: 1505: 1499: 1493: 1487: 1478: 1472: 1453: 1450:Chan-Smutko 2012 1447: 1438: 1432: 1391: 1385: 1330: 1324: 1307: 1301: 1264: 1258: 1223: 1217: 1055:Patient registry 987:skin resurfacing 646:tumor suppressor 604:carboxy terminus 511:tonsillar cancer 356:renal oncocytoma 269:epidermoid cysts 231: 222: 169:German Shepherds 157:tumor suppressor 102:genetic disorder 72: 71: 63:Medical genetics 47: 35: 21: 3089: 3088: 3084: 3083: 3082: 3080: 3079: 3078: 3044: 3043: 3040: 3035: 3013: 2985: 2957: 2850: 2811:Nevus sebaceous 2803:Sebaceous gland 2793: 2757: 2707: 2646: 2637: 2599:BHDSyndrome.org 2595: 2590: 2589: 2555: 2554: 2517: 2503: 2498: 2469: 2430: 2410: 2371: 2363: 2361: 2351: 2331: 2314:Anticancer Res. 2307: 2276: 2268: 2266: 2255: 2226: 2190: 2142: 2134: 2132: 2118: 2113: 2100: 2072: 2064: 2062: 2049: 2041: 2039: 2030: 1992: 1954: 1926: 1898: 1890: 1888: 1887:on 11 June 2021 1877: 1849: 1821: 1812: 1811: 1805: 1801: 1795: 1791: 1785:Liu et al. 2013 1783: 1779: 1771: 1767: 1759: 1755: 1747: 1743: 1735: 1731: 1725:Riegert-Johnson 1723: 1719: 1711: 1707: 1699: 1695: 1689:Ayo et al. 2007 1687: 1683: 1622: 1621: 1617: 1609: 1605: 1597: 1590: 1580: 1578: 1570: 1569: 1565: 1557: 1544: 1536: 1532: 1524: 1520: 1512: 1508: 1500: 1496: 1488: 1481: 1473: 1456: 1448: 1441: 1433: 1394: 1386: 1333: 1325: 1310: 1302: 1267: 1259: 1226: 1218: 1209: 1199: 1095: 1069: 1057: 1044: 975: 959:Cowden syndrome 939:cystic fibrosis 923:Marfan syndrome 891: 866: 864:Genetic testing 837: 831: 819:genetic testing 815: 635: 606:. Very rarely, 552: 547: 545:Pathophysiology 499:trichoblastomas 442:Thyroid nodules 439: 425:or generalized 388: 380:kidney function 332: 286:(tumors of the 263:with a plug of 241: 240: 239: 238: 234: 233: 232: 224: 223: 212: 207: 196:medical imaging 122:pulmonary cysts 66: 33: 28: 23: 22: 15: 12: 11: 5: 3087: 3085: 3077: 3076: 3074:Rare syndromes 3071: 3066: 3061: 3056: 3046: 3045: 3037: 3036: 3034: 3033: 3027: 3025: 3019: 3018: 3015: 3014: 3012: 3011: 3006: 3001: 2995: 2993: 2987: 2986: 2984: 2983: 2978: 2973: 2968: 2962: 2959: 2958: 2956: 2955: 2950: 2945: 2940: 2935: 2930: 2925: 2920: 2915: 2913:Trichoblastoma 2910: 2905: 2904: 2903: 2898: 2893: 2888: 2878: 2868: 2862: 2856: 2855: 2852: 2851: 2849: 2848: 2843: 2838: 2833: 2828: 2823: 2818: 2813: 2807: 2805: 2799: 2798: 2795: 2794: 2792: 2791: 2786: 2777: 2771: 2769: 2759: 2758: 2756: 2755: 2753:Apocrine nevus 2750: 2745: 2740: 2735: 2730: 2729: 2728: 2717: 2715: 2709: 2708: 2706: 2705: 2700: 2695: 2690: 2685: 2680: 2674: 2672: 2663: 2654: 2648: 2647: 2638: 2636: 2635: 2628: 2621: 2613: 2607: 2606: 2601: 2592: 2591: 2588: 2587: 2576: 2564: 2563: 2561: 2557: 2556: 2553: 2552: 2541: 2530: 2518: 2513: 2512: 2510: 2509:Classification 2502: 2501:External links 2499: 2497: 2496: 2467: 2428: 2408: 2369: 2349: 2329: 2305: 2274: 2258:BHD Foundation 2253: 2224: 2188: 2140: 2116: 2111: 2098: 2070: 2047: 2028: 1990: 1952: 1924: 1896: 1880:BHD Foundation 1875: 1858:(12): 1674–7, 1847: 1818: 1810: 1809: 1799: 1789: 1777: 1765: 1753: 1749:BHD Foundation 1741: 1729: 1717: 1705: 1693: 1681: 1615: 1603: 1588: 1563: 1542: 1530: 1528:, p. 481. 1518: 1506: 1504:, p. 442. 1494: 1479: 1477:, p. 482. 1454: 1452:, p. 345. 1439: 1392: 1331: 1308: 1265: 1224: 1206: 1205: 1198: 1195: 1172:rhabdomyolysis 1165:salivary gland 1094: 1091: 1068: 1065: 1056: 1053: 1043: 1040: 1028:Knockout mouse 991:laser ablation 983:shave excision 974: 971: 890: 887: 865: 862: 830: 829:Clinical triad 827: 814: 811: 634: 631: 551: 548: 546: 543: 438: 435: 387: 384: 331: 328: 284:trichodiscomas 245:hair follicles 236: 235: 226: 225: 217: 216: 215: 214: 213: 211: 208: 206: 203: 130:hair follicles 74: 73: 60: 54: 53: 49: 48: 40: 39: 31: 26: 24: 14: 13: 10: 9: 6: 4: 3: 2: 3086: 3075: 3072: 3070: 3067: 3065: 3062: 3060: 3057: 3055: 3052: 3051: 3049: 3042: 3032: 3029: 3028: 3026: 3024: 3020: 3010: 3007: 3005: 3002: 3000: 2997: 2996: 2994: 2992: 2988: 2982: 2979: 2977: 2974: 2972: 2969: 2967: 2964: 2963: 2960: 2954: 2951: 2949: 2946: 2944: 2943:Trichoadenoma 2941: 2939: 2936: 2934: 2931: 2929: 2926: 2924: 2923:Trichilemmoma 2921: 2919: 2916: 2914: 2911: 2909: 2908:Trichodiscoma 2906: 2902: 2899: 2897: 2894: 2892: 2889: 2887: 2884: 2883: 2882: 2879: 2877: 2873: 2872:Pilomatricoma 2870: 2869: 2866: 2863: 2861: 2857: 2847: 2844: 2842: 2839: 2837: 2834: 2832: 2829: 2827: 2824: 2822: 2819: 2817: 2814: 2812: 2809: 2808: 2806: 2804: 2800: 2790: 2787: 2785: 2781: 2778: 2776: 2773: 2772: 2770: 2768: 2764: 2760: 2754: 2751: 2749: 2746: 2744: 2741: 2739: 2736: 2734: 2731: 2727: 2724: 2723: 2722: 2719: 2718: 2716: 2714: 2710: 2704: 2701: 2699: 2696: 2694: 2691: 2689: 2688:Eccrine nevus 2686: 2684: 2681: 2679: 2676: 2675: 2673: 2671: 2667: 2664: 2662: 2658: 2655: 2653: 2649: 2645: 2641: 2634: 2629: 2627: 2622: 2620: 2615: 2614: 2611: 2605: 2602: 2600: 2597: 2596: 2586: 2582: 2581: 2577: 2575: 2571: 2570: 2566: 2565: 2562: 2558: 2551: 2547: 2546: 2542: 2540: 2536: 2535: 2531: 2529: 2525: 2524: 2520: 2519: 2516: 2511: 2507: 2500: 2494: 2490: 2486: 2482: 2479:(5): 701–10, 2478: 2474: 2468: 2465: 2461: 2456: 2451: 2447: 2443: 2440:(6): 321–31, 2439: 2435: 2429: 2426: 2422: 2418: 2414: 2409: 2406: 2402: 2397: 2392: 2388: 2384: 2381:(2): 244–51, 2380: 2376: 2370: 2359: 2355: 2350: 2347: 2343: 2339: 2335: 2330: 2327: 2323: 2319: 2315: 2311: 2306: 2303: 2299: 2294: 2289: 2286:(2): 157–64, 2285: 2281: 2275: 2264: 2260: 2259: 2254: 2251: 2247: 2243: 2239: 2235: 2231: 2225: 2222: 2218: 2214: 2210: 2206: 2202: 2198: 2194: 2189: 2186: 2182: 2177: 2172: 2167: 2162: 2158: 2154: 2151:(6): e65869, 2150: 2146: 2141: 2130: 2126: 2122: 2117: 2114: 2108: 2104: 2099: 2096: 2092: 2088: 2084: 2081:(4): 439–48, 2080: 2076: 2071: 2060: 2056: 2052: 2048: 2037: 2033: 2029: 2026: 2022: 2017: 2012: 2008: 2004: 2001:(3): 178–86, 2000: 1996: 1991: 1988: 1984: 1979: 1974: 1970: 1966: 1963:(1): 95–110, 1962: 1958: 1953: 1950: 1946: 1942: 1938: 1935:(5): 478–85, 1934: 1930: 1925: 1922: 1918: 1914: 1910: 1906: 1902: 1897: 1886: 1882: 1881: 1876: 1873: 1869: 1865: 1861: 1857: 1853: 1848: 1845: 1841: 1837: 1833: 1830:(2): 679–84, 1829: 1825: 1820: 1819: 1817: 1816: 1803: 1800: 1793: 1790: 1786: 1781: 1778: 1774: 1769: 1766: 1762: 1757: 1754: 1750: 1745: 1742: 1738: 1733: 1730: 1726: 1721: 1718: 1714: 1709: 1706: 1702: 1697: 1694: 1690: 1685: 1682: 1677: 1673: 1669: 1665: 1660: 1655: 1651: 1647: 1643: 1639: 1635: 1631: 1627: 1619: 1616: 1612: 1607: 1604: 1600: 1595: 1593: 1589: 1577: 1573: 1567: 1564: 1560: 1555: 1553: 1551: 1549: 1547: 1543: 1539: 1534: 1531: 1527: 1522: 1519: 1515: 1510: 1507: 1503: 1498: 1495: 1491: 1486: 1484: 1480: 1476: 1471: 1469: 1467: 1465: 1463: 1461: 1459: 1455: 1451: 1446: 1444: 1440: 1436: 1431: 1429: 1427: 1425: 1423: 1421: 1419: 1417: 1415: 1413: 1411: 1409: 1407: 1405: 1403: 1401: 1399: 1397: 1393: 1389: 1384: 1382: 1380: 1378: 1376: 1374: 1372: 1370: 1368: 1366: 1364: 1362: 1360: 1358: 1356: 1354: 1352: 1350: 1348: 1346: 1344: 1342: 1340: 1338: 1336: 1332: 1328: 1323: 1321: 1319: 1317: 1315: 1313: 1309: 1305: 1300: 1298: 1296: 1294: 1292: 1290: 1288: 1286: 1284: 1282: 1280: 1278: 1276: 1274: 1272: 1270: 1266: 1262: 1257: 1255: 1253: 1251: 1249: 1247: 1245: 1243: 1241: 1239: 1237: 1235: 1233: 1231: 1229: 1225: 1221: 1216: 1214: 1212: 1208: 1204: 1203: 1196: 1194: 1192: 1188: 1183: 1182:Knockout mice 1179: 1177: 1173: 1169: 1166: 1162: 1157: 1152: 1149: 1145: 1144: 1139: 1135: 1132:A homolog of 1130: 1128: 1124: 1120: 1116: 1112: 1108: 1104: 1100: 1093:Other animals 1092: 1090: 1088: 1084: 1078: 1075: 1066: 1064: 1062: 1054: 1052: 1050: 1049:heterogeneous 1041: 1039: 1037: 1033: 1029: 1025: 1021: 1017: 1012: 1008: 1004: 1000: 996: 992: 988: 984: 980: 972: 970: 968: 964: 960: 954: 952: 951:endometriosis 948: 944: 940: 936: 932: 928: 924: 919: 917: 913: 909: 900: 895: 888: 886: 883: 878: 874: 870: 863: 861: 859: 855: 851: 847: 843: 836: 828: 826: 824: 820: 812: 810: 807: 804: 800: 796: 792: 791:tumorigenesis 788: 784: 779: 775: 770: 766: 762: 754: 750: 745: 741: 739: 735: 731: 727: 723: 717: 715: 711: 707: 703: 699: 695: 691: 687: 683: 679: 675: 671: 667: 663: 659: 658:parotid gland 655: 651: 647: 643: 639: 632: 630: 628: 624: 620: 618: 613: 609: 605: 601: 597: 593: 589: 585: 584:chromosome 17 581: 577: 569: 565: 561: 556: 549: 544: 542: 540: 536: 532: 528: 524: 520: 516: 512: 508: 504: 500: 497:of the face, 496: 495:angiofibromas 492: 488: 487:neurothekeoma 484: 480: 476: 472: 468: 464: 460: 456: 452: 448: 443: 436: 434: 432: 428: 424: 420: 419:lung function 416: 412: 408: 405: 401: 397: 393: 385: 383: 381: 377: 373: 367: 365: 361: 357: 353: 349: 341: 340:H&E stain 336: 329: 327: 325: 321: 317: 313: 309: 305: 304:buccal mucosa 301: 297: 293: 292:angiofibromas 289: 285: 280: 278: 274: 270: 267:, or include 266: 262: 258: 254: 250: 246: 230: 221: 209: 204: 202: 200: 197: 193: 189: 184: 182: 178: 174: 170: 166: 162: 158: 154: 150: 146: 141: 139: 135: 131: 127: 123: 119: 115: 114:kidney cancer 111: 107: 103: 100: 96: 92: 88: 84: 80: 70: 64: 61: 59: 55: 50: 46: 41: 36: 30: 19: 3041: 2980: 2953:Dilated pore 2743:Hidrocystoma 2578: 2567: 2543: 2532: 2521: 2476: 2472: 2437: 2433: 2416: 2378: 2374: 2362:, retrieved 2357: 2337: 2320:(3): 751–7, 2317: 2313: 2283: 2279: 2267:, retrieved 2263:the original 2257: 2233: 2229: 2199:(1): e21–6, 2196: 2192: 2148: 2144: 2133:, retrieved 2129:the original 2124: 2102: 2078: 2074: 2063:, retrieved 2059:the original 2054: 2040:, retrieved 2035: 1998: 1994: 1960: 1956: 1932: 1928: 1907:(4): 343–9, 1904: 1900: 1889:, retrieved 1885:the original 1879: 1855: 1851: 1827: 1823: 1815:Bibliography 1814: 1813: 1802: 1792: 1780: 1768: 1756: 1744: 1737:Kniffin 2012 1732: 1720: 1708: 1696: 1684: 1633: 1629: 1618: 1606: 1579:. Retrieved 1575: 1566: 1533: 1521: 1516:, p. 4. 1509: 1497: 1261:Andrews 2011 1201: 1200: 1190: 1186: 1180: 1175: 1155: 1153: 1147: 1141: 1137: 1133: 1131: 1122: 1118: 1106: 1098: 1096: 1079: 1070: 1058: 1045: 1042:Epidemiology 1035: 976: 955: 920: 904: 868: 867: 857: 838: 822: 816: 808: 802: 798: 794: 773: 768: 760: 758: 748: 721: 718: 702:mitochondria 682:noncancerous 677: 637: 636: 626: 616: 591: 575: 573: 475:angiolipomas 446: 440: 437:Other organs 415:pneumothorax 402:) in the sub 389: 368: 360:kidney cysts 345: 316:acrochordons 312:Collagenomas 281: 242: 185: 180: 160: 148: 145:genetic test 142: 109: 94: 90: 86: 82: 78: 77: 29: 2698:Spiradenoma 2661:Sweat gland 2580:GeneReviews 2417:GeneReviews 2280:Cancer Cell 1581:13 November 1170:as well as 1161:endometrial 1020:nephrectomy 1007:ultrasounds 860:mutations. 850:chromophobe 783:chromophobe 732:, normally 491:meningiomas 165:fruit flies 3048:Categories 2721:Cylindroma 2545:DiseasesDB 1599:Maher 2011 1197:References 973:Management 875:in 88% of 873:sequencing 854:oncocytoma 833:See also: 787:oncocytoma 730:amino acid 724:is highly 623:penetrance 308:epithelium 153:folliculin 106:folliculin 2991:Hamartoma 2846:Mantleoma 2831:Sebaceoma 2775:Syringoma 2569:eMedicine 1676:220289684 1388:Toro 2008 1202:Citations 1087:neoplasms 1032:rapamycin 1016:radiation 979:curettage 842:histology 813:Diagnosis 738:orthologs 726:conserved 694:rapamycin 660:, brain, 431:emphysema 322:, on the 288:hair disc 253:outer ear 132:, called 58:Specialty 2767:apocrine 2713:Apocrine 2574:derm/622 2493:20817385 2464:18234728 2425:20301695 2405:23063455 2346:21249760 2326:20392993 2302:12204536 2250:19959076 2221:23464317 2213:21071978 2185:23799055 2145:PLOS ONE 2095:19264190 2025:23223565 1987:22365249 1949:19584731 1921:22846736 1844:17505035 1668:32612235 1191:in utero 1103:ortholog 877:probands 670:prostate 666:pancreas 650:nephrons 642:isoforms 633:Function 619:mutation 588:cytosine 550:Genetics 523:melanoma 409:base or 350:tumors ( 85:), also 2763:Eccrine 2670:Eccrine 2539:D058249 2455:2564862 2396:3709870 2364:21 July 2269:25 July 2176:3684598 2153:Bibcode 2135:13 July 2065:25 July 2042:13 July 2016:3595143 1978:3292740 1891:17 July 1659:7610377 1638:Bibcode 1067:History 846:CT scan 706:complex 674:ovaries 617:de novo 560:gametes 519:sarcoma 471:lipomas 404:pleural 330:Kidneys 324:eyelids 300:papules 265:keratin 257:plaques 128:of the 2652:Glands 2640:Tumors 2528:135150 2491: 2462: 2452: 2423: 2403: 2393: 2360:, NCBI 2344: 2324: 2300: 2248: 2219: 2211: 2183: 2173: 2109: 2093: 2023: 2013: 1985: 1975: 1947: 1919: 1872:596896 1870: 1842: 1674: 1666: 1656: 1630:Nature 1136:called 965:, and 937:, and 882:exonic 734:lysine 672:, and 662:breast 652:, and 537:, and 400:bullae 348:kidney 320:armpit 294:, and 261:comedo 175:, and 124:, and 93:, and 65: 3023:Nails 2550:33274 2217:S2CID 1824:Chest 1672:S2CID 1138:DBHD 1119:FLCN 1009:, or 989:, or 774:FLCN 753:p arm 708:with 564:sperm 396:blebs 392:cysts 386:Lungs 273:sebum 118:renal 2860:Hair 2642:and 2534:MeSH 2523:OMIM 2489:PMID 2460:PMID 2421:PMID 2401:PMID 2366:2009 2342:PMID 2322:PMID 2298:PMID 2271:2013 2246:PMID 2209:PMID 2181:PMID 2137:2013 2107:ISBN 2091:PMID 2067:2013 2044:2013 2021:PMID 1983:PMID 1945:PMID 1917:PMID 1893:2013 1868:PMID 1840:PMID 1664:PMID 1583:2021 1187:FLCN 1176:FLCN 1163:and 1156:FLCN 1148:DBHD 1134:FLCN 1123:FLCN 1107:FLCN 1099:FLCN 1085:and 1047:are 1036:FLCN 1011:MRIs 945:and 869:FLCN 858:FLCN 823:FLCN 803:FLCN 799:FLCN 795:FLCN 769:FLCN 761:FLCN 749:FLCN 722:FLCN 690:mTOR 678:FLCN 638:FLCN 627:FLCN 592:FLCN 580:exon 576:FLCN 566:and 447:FLCN 407:lung 374:and 354:and 210:Skin 181:FLCN 177:mice 173:rats 161:FLCN 149:FLCN 120:and 110:FLCN 2481:doi 2450:PMC 2442:doi 2391:PMC 2383:doi 2288:doi 2238:doi 2201:doi 2197:118 2171:PMC 2161:doi 2083:doi 2011:PMC 2003:doi 1973:PMC 1965:doi 1937:doi 1909:doi 1860:doi 1856:113 1832:doi 1828:132 1654:PMC 1646:doi 1634:585 1159:to 1105:of 700:in 598:or 568:egg 398:or 358:), 338:An 83:BHD 3050:: 2583:: 2572:: 2548:: 2537:: 2526:: 2487:, 2477:58 2475:, 2458:, 2448:, 2438:45 2436:, 2399:, 2389:, 2379:63 2377:, 2356:, 2318:30 2316:, 2312:, 2296:, 2282:, 2244:, 2234:10 2232:, 2215:, 2207:, 2195:, 2179:, 2169:, 2159:, 2147:, 2123:, 2089:, 2079:64 2077:, 2053:, 2034:, 2019:, 2009:, 1999:66 1997:, 1981:, 1971:, 1961:33 1959:, 1943:, 1933:19 1931:, 1915:, 1905:18 1903:, 1866:, 1854:, 1838:, 1826:, 1670:. 1662:. 1652:. 1644:. 1632:. 1628:. 1591:^ 1574:. 1545:^ 1482:^ 1457:^ 1442:^ 1395:^ 1334:^ 1311:^ 1268:^ 1227:^ 1210:^ 1193:. 1129:. 1026:. 1001:. 985:, 981:, 961:, 933:, 929:, 925:, 852:, 716:. 668:, 664:, 541:. 533:, 529:, 525:, 517:, 513:, 505:, 501:, 493:, 489:, 485:, 481:, 477:, 473:, 469:, 465:, 461:, 457:, 453:, 310:. 279:. 201:. 171:, 167:, 116:, 89:, 2874:/ 2782:/ 2765:/ 2632:e 2625:t 2618:v 2515:D 2483:: 2444:: 2385:: 2290:: 2284:2 2240:: 2203:: 2163:: 2155:: 2149:8 2085:: 2005:: 1967:: 1939:: 1911:: 1862:: 1834:: 1787:. 1775:. 1763:. 1751:. 1739:. 1727:. 1715:. 1703:. 1691:. 1678:. 1648:: 1640:: 1613:. 1601:. 1585:. 1561:. 1540:. 1492:. 1437:. 1390:. 1329:. 1306:. 1263:. 1222:. 562:( 394:( 247:( 108:( 81:( 20:)

Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.

Knowledge

Birt–Hogg–Dubé syndrome

Index