Bazex-Dupr�-Christol syndrome, another rare genodermatosis associated with development of BCC, has more thorough documentation in the literature than Rombo syndrome. Inheritance is accomplished in an X-linked dominant fashion, with no reported male-to-male transmission.[108,109,110] Regional assignment of the locus of interest to chromosome Xq24-q27 is associated with a maximum LOD score of 5.26 with the DXS1192 locus.
Characteristic physical findings include hypotrichosis, hypohidrosis, milia, follicular atrophoderma of the cheeks, and multiple BCC, which manifest in the late second decade to early third decade. Documented hair changes with Bazex-Dupr�-Christol syndrome include reduced density of scalp and body hair, decreased melanization, a twisted/flattened appearance of the hair shaft on electron microscopy, and increased hair shaft diameter on polarizing light microscopy. The milia, which may be quite distinctive in childhood, have been reported to regress or diminish substantially at puberty. Other reported findings in association with this syndrome include trichoepitheliomas, hidradenitis suppurativa, hypoplastic alae, and a prominent columella.[114,115]
Epidermolysis bullosa simplex, Dowling-Meara
A rare subtype of epidermolysis bullosa simplex (EBS), Dowling-Meara (EBS-DM), is inherited in an autosomal dominant fashion and is associated with mutations in either keratin-5 (KRT5) or keratin-14 (KRT14). It is one of the most severe types of EBS and results in occasional mortality in early childhood. One report cites an incidence of BCC of 44% by age 55 years in this population. Other less phenotypically severe subtypes of EBS can also be caused by mutations in either KRT5 or KRT14.
Characteristics of hereditary syndromes associated with a predisposition to BCC are described in Table 2 below.
Table 2. Basal Cell Carcinoma (BCC) Syndromes
AD = autosomal dominant; AR = autosomal recessive; OMIM = Online Mendelian Inheritance in Man; XD = X-linked dominant.
|Syndrome (OMIM link)||Inheritance||Chromosome||Gene||Clinical Findings|
|Basal cell nevus syndrome, Gorlin syndrome||AD||9q22.3-q31||PTCH1[119,120]||BCC (before age 20 y)|
|Rombo syndrome||AD||�||�||Milia, atrophoderma vermiculatum, acrocyanosis, trichoepitheliomas, and BCC (age 30-40 y)|
|Bazex-Dupr�-Christol syndrome ||XD > AD||Xq24-27||Unknown||Hypotrichosis (variable), hypohidrosis, milia, follicular atrophoderma (dorsal hands), and multiple BCCs (aged teens to early 20s)|
|Brooke-Spiegler syndrome||AD||16q12-q13[122,123]||CYLD[124,125]||Cylindroma (forehead, scalp, trunk, and pubic area),[126,127] trichoepithelioma (around nose), spiradenoma, and BCC |
|Multiple hereditary infundibulocystic BCC||AD||Unknown||Unknown||Multiple BCC (infundibulocystic type)|
|Schopf-Schultz-Passarge syndrome||AR > AD||Unknown||Unknown||Ectodermal dysplasia (hypotrichosis, hypodontia, and nail dystrophy [anonychia and trachyonychia]), hidrocystomas of eyelids, palmo-plantar keratosis and hyperhidrosis, and BCC|
Refer to the section on Brooke-Spiegler Syndrome, Multiple Familial Trichoepithelioma, and Familial Cylindromatosis for more information about Brooke-Spiegler syndrome.