A 10-year-old girl is referred to dermatology for evaluation of multiple skin-colored papules on her face and neck that began appearing over the past year. Her parents mention she has had jaw swelling in the past, and a recent dental evaluation revealed a radiolucent lesion in the mandible. She also has palmar pits noted on examination. A review of systems reveals a history of macrocephaly, and a recent ophthalmologic exam showed strabismus.

Which of the following findings is most characteristic of this patient’s underlying condition?

A. Epidermoid inclusion cysts on the scalp

B. Histologic confirmation of multiple syringomas

C. Basal cell carcinomas arising before puberty

D. Hyperkeratotic plaques with follicular plugging

E. Spontaneous resolution of lesions by adolescence

Rationale: 

This clinical vignette is consistent with basal cell nevus syndrome (BCNS), or Gorlin syndrome, a rare autosomal dominant disorder caused most commonly by PTCH1 mutations (part of the hedgehog signaling pathway). It is characterized by multiple basal cell carcinomas (BCCs) arising at an unusually young age — even in childhood or adolescence, odontogenic keratocysts (jaw cysts), palmar/plantar pits, craniofacial abnormalities (e.g. macrocephaly, frontal bossing, hypertelorism), skeletal anomalies (e.g. bifid ribs), and ocular findings (e.g. strabismus, coloboma). Treatment of basal cell carcinomas can be difficult given the shear number of neoplasms that develop over a patient's lifetime and surgical fatigue that occurs. These patients require interdisciplinary management, including dermatology, oral surgery, genetics, and often oncology.

Correct answer: C. Basal cell carcinomas arising before puberty. 

These are a hallmark of basal cell nevus syndrome and children may develop dozens to hundreds of BCCs by adolescence. It should be noted that in children, these can frequently appear identical to skin tags and histologic confirmation is often helpful to determine if they are skin tags or basal cell carcinomas. 

Incorrect answer choices:

A. Epidermoid inclusion cysts on the scalp are common in the general population but not a hallmark of BCNS. This would not explain the constellation of findings in this case.

B. Histologic confirmation of multiple syringomas. Syringomas are benign adnexal tumors, often periocular in adolescents, but not associated with jaw cysts or palmar pits.

D. Hyperkeratotic plaques with follicular plugging describes findings in keratosis pilaris or lichen planopilaris, not BCNS.

E. Spontaneous resolution of lesions by adolescence is incorrect because lesions in BCNS typically increase over time, and BCCs continue developing into adulthood.

Additional reading at Fitzpatrick's Dermatology Chapter 111: Basal Cell Carcinoma and Basal Cell Nevus Syndrome