Bazex-Dupré-Christol syndrome
BDCS; "follicular atrophoderma and basal cell carcinomas"; one of the differential diagnoses in any young patient with multiple early BCCs (Gorlin, Rombo, BDCS)
Bazex-Dupré-Christol syndrome is a rare X-linked dominant cancer-predisposition disorder mapped to chromosome Xq25-q27. The causative variant remains debated: ACTRT1 and regulatory elements in the ACTRT1 / UBE2A region have been proposed, but BDCS should still be presented as a clinically defined syndrome rather than a fully settled single-gene disorder. It is characterised by the distinctive combination of multiple early-onset basal cell carcinomas (median age ~20 years, decades earlier than sporadic BCC), follicular atrophoderma (multiple "ice-pick" depressions on the dorsa of the hands and feet), congenital hypotrichosis (sparse hair on the scalp, eyebrows and eyelashes from infancy) and hypohidrosis. Distinguishing BDCS from Gorlin syndrome (PTCH1, autosomal dominant, jaw cysts, palmar pits, medulloblastoma) and Rombo syndrome (autosomal dominant, vermiculate atrophoderma of the cheeks) is the principal diagnostic challenge. Lifelong dermatological surveillance, rigorous photoprotection and surgical management of the recurrent BCCs are the cornerstones of care.
Genetics
- X-linked dominant inheritance with apparent male preponderance for severe expression (lethal in some hemizygous male foetuses).
- Locus mapped to chromosome Xq25-q27.
- ACTRT1 and nearby regulatory elements in the ACTRT1 / UBE2A region have been proposed, but the molecular basis is not fully settled across families.
- Diagnosis is primarily clinical, supported by specialist clinical genetics assessment and panel testing where available; a negative single-gene result does not exclude the phenotype.
Cardinal clinical features
- Multiple early-onset basal cell carcinomas:
- Onset in second / third decade (vs sixth–seventh decade for sporadic BCC).
- Predilection for the face — particularly the central face and periorbital region.
- Multiple synchronous and metachronous lesions through life (often dozens by middle age).
- Histology — typical superficial / nodular / pigmented / morphoeic BCC.
- Follicular atrophoderma:
- Multiple small depressed "ice-pick" follicular openings on the dorsa of the hands and feet, occasionally face and elbows.
- Present from infancy / early childhood.
- Clinically distinctive — the diagnostic clue that should prompt syndrome workup in a child with hypotrichosis.
- Congenital hypotrichosis:
- Sparse, fine, slow-growing scalp hair from infancy.
- Sparse eyebrows and eyelashes.
- Hypohidrosis — reduced sweating affecting the trunk and limbs; heat intolerance.
- Other features — milia (especially on the face), trichoepitheliomas in some patients, hair-shaft anomalies (pili torti).
Differential diagnosis — multiple early BCC syndromes
- Gorlin syndrome (naevoid BCC syndrome) — autosomal dominant PTCH1; multiple BCCs + palmar pits + jaw odontogenic keratocysts + medulloblastoma + bifid ribs + falx calcification — see monograph.
- Rombo syndrome — autosomal dominant; multiple BCCs + vermiculate atrophoderma of the cheeks + milia + hypotrichosis + peripheral cyanosis; see next section.
- Bazex paraneoplastic acrokeratosis — entirely different entity; psoriasiform paraneoplastic eruption associated with upper aerodigestive SCC — see Bazex acrokeratosis.
- Xeroderma pigmentosum — autosomal recessive; severe early-onset BCC, cSCC and melanoma — see monograph.
- Multiple familial trichoepithelioma / Brooke-Spiegler syndrome — see monograph — multiple trichoepitheliomas can be confused with BCCs.
Management
- Multidisciplinary care — dermatology, plastic surgery, clinical genetics; lifelong.
- Photoprotection — broad-spectrum SPF 50+ daily, sun-protective clothing; vitamin D supplementation as needed.
- Annual / 6-monthly full-skin surveillance from adolescence; lower threshold for biopsy of any new lesion.
- Surgical management of individual BCCs:
- Excisional surgery with full histology.
- Mohs micrographic surgery for facial / cosmetically important sites.
- Topical / destructive therapies (imiquimod, 5-FU, PDT, cryotherapy) for selected superficial BCCs.
- Hedgehog pathway inhibitors (vismodegib, sonidegib) — case reports of meaningful response in BDCS; reserve for unresectable / recurrent disease — see vismodegib.
- Cosmetic management of facial BCCs and hypotrichosis (wigs, eyebrow tattooing) as desired.
- Cooling strategies for hypohidrosis — particularly relevant in hot climates and during exercise.
- Genetic counselling and cascade testing.
References
- Vabres P et al. The gene for Bazex-Dupré-Christol syndrome maps to chromosome Xq. J Invest Dermatol; 1995.
- Bal E et al. Mutations in ACTRT1 and its enhancer RNA elements lead to aberrant activation of Hedgehog signalling in inherited and sporadic basal cell carcinomas. Nat Med; 2017.
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