Genetics

Germline loss-of-function mutations of FLCN on chromosome 17p11.2 — encoding folliculin, a tumour suppressor implicated in mTOR, AMPK and HIF signalling.
Autosomal dominant; high penetrance for skin lesions and pulmonary cysts; variable for RCC.
De novo mutations are relatively common.
Most pathogenic mutations affect a hotspot in exon 11 — the so-called "C8 tract".

Mucocutaneous features

Fibrofolliculomas — multiple (often dozens to hundreds), small (1–3 mm), skin-coloured to white, dome-shaped papules concentrated on the face (nose, cheeks, forehead, ears), neck and upper trunk. Onset typically third to fourth decade.
Trichodiscomas — clinically indistinguishable from fibrofolliculomas; histologically distinct (perifollicular fibrous proliferation).
Acrochordons (skin tags) — multiple in unusual sites and from a young age (axillae, neck, eyelids).
Oral fibromas — papules on the gums, lips and buccal mucosa.
Histology of fibrofolliculoma: anastomosing strands of basaloid epithelium emanating from a central hair follicle, embedded in a fibromucinous stroma — pathognomonic.

Multiple, irregular, basal and subpleural pulmonary cysts on CT in >80% of adults.
Lifetime risk of spontaneous pneumothorax ~30–40% — frequently the presenting feature; recurrent in many.
Cysts are not progressive and rarely cause respiratory impairment, but the pneumothorax risk is substantial.
Counsel patients to avoid smoking, scuba diving and high-altitude flight without medical clearance.

Lifetime renal cell carcinoma risk ~25–35%; median age at diagnosis 50–60.
Histological subtypes are characteristically chromophobe RCC (~30%) or hybrid oncocytic / chromophobe (~50%) tumours; oncocytoma also overrepresented.
Often bilateral and multifocal (multiple synchronous tumours).
Generally indolent — but metastatic disease is well-described and renal screening is the single most important preventive intervention.

Suspect in any patient with multiple fibrofolliculomas, family history of pneumothorax / RCC, or unusual skin tags from a young age.
Clinical European BHD Foundation diagnostic criteria — major criteria (≥5 fibrofolliculomas/trichodiscomas with ≥1 histologically confirmed; pathogenic FLCN mutation) and minor criteria.
Skin biopsy of a representative facial papule.
Genetic counselling and germline FLCN testing.
Cascade testing of first-degree relatives.

Renal — annual or biennial MRI of the kidneys from age 20–25, lifelong; ultrasound is less sensitive and not preferred.
Pulmonary — baseline CT chest at diagnosis; counsel about pneumothorax symptoms; no role for surveillance imaging beyond baseline unless symptomatic.
Skin — annual full-skin examination; cosmetic management of facial fibrofolliculomas as desired.

Skin: cosmetic management — CO₂ laser ablation, electrosurgery, dermabrasion, shave excision; recurrence common; topical sirolimus emerging.
Pneumothorax: standard chest-drain management; consider VATS pleurodesis after second event.
RCC: nephron-sparing partial nephrectomy preferred (often bilateral / multifocal disease over a lifetime); active surveillance for <3 cm tumours given indolent biology; targeted / immunotherapy as per RCC protocols for advanced disease.
Multidisciplinary care — dermatology, urology, respiratory medicine, clinical genetics.