White facial papules and sparse, brittle hair

Bazex-Dupré-Christol syndrome (BDCS), also known as Bazex syndrome, is a rare genodermatosis characterized by the triad of hypotrichosis, basal cell carcinoma (BCC) and follicular atrophoderma. As of 2006, only 138 cases of BDCS have been reported.1 Because of the rarity...

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Bazex-Dupré-Christol syndrome (BDCS), also known as Bazex syndrome, is a rare genodermatosis characterized by the triad of hypotrichosis, basal cell carcinoma (BCC) and follicular atrophoderma. As of 2006, only 138 cases of BDCS have been reported.¹ Because of the rarity of this disease, the incidence or prevalence has not been well-established. Males and females can be affected. A large number of families with this syndrome originate from Central Europe, primarily France and Belgium.²

BDCS is thought to be inherited in an X-linked dominant fashion, as no male-to-male transmission has been reported and almost all daughters of affected fathers are affected.¹ The gene mutation has been previously linked to Xq24-q27; however, more recent studies have narrowed the candidate region to chromosome Xq25-27.1. The pathogenic mutation has yet to be identified.^3,4

The diagnosis of BDCS can be difficult because clinical findings present at different ages. Hypotrichosis is a congenital feature and is one of the earliest signs of this genodermatosis. Hair abnormalities may be seen on the scalp, eyelashes, eyebrows, and axillary and pubic areas. It is estimated that 85% of all patients with BDCS demonstrate some hair-shaft abnormality.

Microscopic examination of the hair can reveal broken shafts, trichorrhexis nodosa, and/or pili bifurcati.⁵ Hair can become more abundant with age but often remains sparse and fragile.⁵ Milia are present in 66% of patients and can appear in infancy. The number of milia can range from a few isolated lesions to hundreds of papules on the face and trunk.

Follicular atrophoderma is seen in the majority of, but not all, cases and presents as atrophic ice-pick follicular depressions, most commonly on the dorsal hands. Follicular atrophoderma may also be seen on the dorsal feet, face, and extensor surfaces of the elbows and knees. It is unclear whether follicular atrophoderma is present at birth, but it does tend to present in early childhood.

The most worrisome characteristic of BDCS is the association with BCC. Although part of the classic clinical triad describing BDCS, BCC develops only in 28% of patients.⁵ BCCs typically develop in the second to third decade of life, but the onset may range from age 9 years to age 50 years. The most common location of BCC is on the face.⁶

Hypohidrosis is another characteristic finding but may only be present in 25% of patients. Hypohidrosis may be generalized or localized to the face. In approximately 10% of patients, basal cell nevi and trichoepitheliomas may be seen. These neoplasms are usually seen on the face; however, trichoepitheliomas on the genitalia have been reported.⁷

The diagnosis of BDCS is made clinically, as genetic testing is not available at this time. Hair samples are rarely obtained because the microscopic findings are nonspecific and highly varied. It is rather the qualitative findings of hair sparsity and brittleness that characterize BDCS. Skin biopsies may be performed to confirm clinical findings.

The histology of milia is that of tiny epidermoid cysts. The cystic spaces seen on skin biopsy are located in the superficial dermis and are lined by stratified squamous epithelium. The cyst contains varied amounts of lamellated keratin. On skin biopsy, follicular atrophoderma is notable for a depression in the epidermis with the absence of hair structures.⁶

Suspected BCCs require biopsy. The characteristic histologic findings of BCC include islands of basaloid cells with peripheral palisading and stromal retraction. Trichoepitheliomas are also notable for islands of basaloid cells and peripheral palisading, but these neoplasms lack the stromal retraction seen in BCCs. Trichoepitheliomas also can be distinguished from BCCs by the presence of keratin-filled cysts and papillary-mesenchymal bodies, which are rudimentary follicular papillae.

The differential diagnosis varies based on the time of presentation. If a patient presents in infancy, only such early findings as hypotrichosis, follicular atrophoderma, or milia may be present. The differential diagnosis in infancy includes Rombo syndrome and X-linked dominant chondrodysplasia punctata.

Rombo syndrome is a genodermatosis inherited in an autosomal-dominant fashion. Rombo syndrome is also characterized by hypotrichosis, milia, and BCCs; however, unlike BDCS, this syndrome is notable for hyperhidrosis and vermicular atrophoderma (atrophic scarring on the cheeks); cyanotic redness of the face, lips, and hands; and short stature.¹

X-linked chondrodysplasia punctata also presents with follicular atrophoderma and abnormal hair, but such highly characteristic findings as asymmetric shortening of the limbs, striated hyperkeratosis, and pigmentary defects of the skin make the clinical distinction from BDCS relatively easy.

If a patient presents later in life with multiple BCCs, the differential diagnosis would include Gorlin syndrome. Gorlin syndrome, also known as nevoid BCC syndrome, is notable for multiple BCCs. Patients with Gorlin syndrome often have characteristic macrocephaly, frontal bossing, hypertelorism, and palmar pits, which are not seen in BDCS. The early diagnosis of Gorlin syndrome is especially important due to the increased risk for the development of medulloblastoma in early childhood.

Because of the risk of BCC, individuals with BDCS should be evaluated at least once per year. Typically, the only findings patients seek treatment for are BCC and milia. Treatment of BCC depends on several factors, including histologic type, patient preference, and tumor size and location. The preferred methods of treatment for most BCCs include curettage or local excision.

Superficial BCCs may be treated with topical imiquimod 5% (Aldara) cream applied five nights a week for six weeks. High-risk histologic types (i.e., infiltrative, morpheaform, micronodular), recurrent BCCs, or lesions on cosmetically sensitive areas should be referred for Mohs micrographic surgery or to a plastic surgeon.

Milia can be treated with incision with a cutting-edge needle and manual expression. There is a case report of eruptive milia successfully being treated with tretinoin 0.1% cream b.i.d. for six weeks.⁸

This patient’s family history, hypotrichosis, milia, and hypohidrosis were consistent with BDCS. Due to the patient’s young age, no treatment for milia was initiated. He will be monitored for the development of BCCs.

Audrey Chan is a third-year dermatology resident at Baylor College of Medicine in Houston.

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