Birt-Hogg-Dubé syndrome

Abstract

A 45-year-old woman with a history of renal carcinoma was observed for facial, cervical and truncal flesh-colored papules. Relatives had similar skin findings and a brother had repeated episodes of pneumothorax. The computerized tomography scan revealed multiple cysts on both lungs. A skin biopsy revealed a perifollicular fibroma. The clinical diagnosis of Birt-Hogg-Dubé syndrome (BHDS) was corroborated by identification of a novel frameshift c.573delGAinsT (p.G191fsX31) mutation in heterozygosity on exon 6 of the folliculin gene. The presence of multiple and typical benign hair follicle tumors highlights the role of the dermatologist in the diagnosis of this rare genodermatosis that is associated with an increased risk of renal cell cancer and pulmonary cysts, warranting personal and familial follow-up and counseling.

Birt-Hogg-Dubé Syndrome – report of two cases with two new mutations

“…Several different FCLN gene mutations have been reported, with unknown phenotype-altering implications. 2 The product of this gene -folliculin -is expressed in many normal tissues, including skin, lung and kidney. [2][3][4] Changes in the activity of this protein, presumably with still unconfirmed tumor suppressor activity (via mTOR signaling), may favour the appearance of several of these skin malformations, lungs cysts and renal cancer.…”

“…[2][3][4] Changes in the activity of this protein, presumably with still unconfirmed tumor suppressor activity (via mTOR signaling), may favour the appearance of several of these skin malformations, lungs cysts and renal cancer. [2][3][4][5] Fibrofolliculoma and TD, the hallmarks of BHDS, are clinically indistinguishable and usually appear in individuals in their 20s or 30s and present as asymptomatic multiple, smooth, skin-colored or whitish, dome-shaped papules commonly located on the face (mainly on the nose, forehead and cheeks) although they can also appear on the neck and trunk. [1][2][3]5 Several authors point out that FF and TD (and even acrochorda) may actually represent different stages of evolution within one same lesion.…”

“…[2][3][4][5] Fibrofolliculoma and TD, the hallmarks of BHDS, are clinically indistinguishable and usually appear in individuals in their 20s or 30s and present as asymptomatic multiple, smooth, skin-colored or whitish, dome-shaped papules commonly located on the face (mainly on the nose, forehead and cheeks) although they can also appear on the neck and trunk. [1][2][3]5 Several authors point out that FF and TD (and even acrochorda) may actually represent different stages of evolution within one same lesion. [1][2][3] In addition to these lesions, the presence of facial angiofibromas has occasionally been reported, as the involvement of oral mucosa in the form of multiple papules involving the lips, buccal mucosa and gingiva.…”

“…[1][2][3]5 Several authors point out that FF and TD (and even acrochorda) may actually represent different stages of evolution within one same lesion. [1][2][3] In addition to these lesions, the presence of facial angiofibromas has occasionally been reported, as the involvement of oral mucosa in the form of multiple papules involving the lips, buccal mucosa and gingiva. 1,3 Although skin lesions are a warming sign for dermatologists, they are not present in all patients with BHDS.…”

“…[1][2][3][4][5][6][7][8][10][11][12] BHDS predisposes to benign hair follicle hamartomas known as fibrofolliculomas (FF) and trichodiscomas (TD), acrochorda; lung disease (bibasilar cysts and, less frequently, pneumothorax); and kidney neoplasms with different histologic presentations. [1][2][3][4][5][6][7][8][10][11][12] The incidence of this syndrome is unknown but it is probably underdiagnosed given its variable penetrance and consequent range of clinical manifestations. 1 We describe two patients with BHDS carrying new FLCN mutations, not previously described in literature, and one of them with a type of adrenal gland tumor associated for the first time to this syndrome.…”