Spitz_Genodermatoses, 3e

Birt-Hogg-Dube Syndrome

Synonym(s)

Fibrofolliculomas with trichodiscomas and acrochordons

Inheritance

AD; FLCN gene encoding folliculin on 17p11.2

Prenatal Diagnosis

DNA mutation analysis

Incidence

> 400 families; most likely underdiagnosed

Age at Presentation

Often > 25 years

Pathogenesis

Protein-truncating mutations in folliculin contribute to phenotype. Recent studies suggest that folliculin acts as a tumor suppressor regulating the mTOR signaling pathway through interactions with other signaling proteins Skin Fibrofolliculomas, trichodiscomas, and acrochordons; increased melanoma risk, including desmoplastic and choroidal melanoma Kidney Multifocal renal tumors, renal cell carcinoma (often bilateral) Lung Recurrent spontaneous pneumothoraces, lung cysts, bullous emphysema Neoplasm Parotid oncocytoma, pleomorphic oncocytoma; thyroid nodules, cancer; colon cancer

Key Features

Differential Diagnosis

Cowden syndrome Tuberous sclerosis Brooke-Spiegler syndrome Rombo syndrome Basaloid follicular hamartoma syndrome

Laboratory Data

Molecular genetic test Skin biopsy

Abdominal magnetic resonance imaging (MRI), renal ultrasound Pulmonary function test (lung cysts not visible on chest x-ray)

Management

Cancer surveillance according to published guidelines; referral to nephrology, pulmonol ogy after thorough history, physical examination, and diagnosis confirmed by dermatolo gist; annual skin examination for melanoma risk Screen all first-degree relatives for kidney and lung manifestations

Prognosis

If renal cell cancer detected early and pulmonary sequelae not debilitating, then good prognosis

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Birt-Hogg-Dube is a syndrome caused by mutations in the gene encoding folliculin . . . As sociated skin tumors—fibrofolliculoma and trichodiscoma—are hamartomas of hair follicle tissue in sebaceous areas . . . Firm, whitish papules on the face, neck, and/or trunk should raise clinical suspicion . . . Although typically numerous, fibrofolliculomas are small and ap pear benign, making them easy to overlook . . . Lesions usually occur after age 25 . . . Specific history should be elicited, including pulmonary disease (including recurrent spontaneous pneumothorax, lung cysts, and/or bullous emphysema) and renal malignancy . . . BHDS is AD so genetics referral for patients followed by at-risk relatives is recommended . . . LE, JH

CLINICAL PEARLS

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