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Becker’s nevus: Mutations that shoulder responsibility

DII small banner By Warren R. Heymann, MD
Aug. 31, 2017

Becker nevus
Systematized, bilateral Becker nevus with hypoplasia of left areola in 19-year-old man (Courtesy of Dr Carlos de la Torre, Pontevedra, Spain).
Credit: JAAD
My wife insisted I take a break from studying for the dermatology boards.
“Warren, give it a rest. Let’s go to the movies. I hear that An Officer and a Gentleman is pretty decent.”

I found myself enjoying the respite until Richard Gere took his shirt off for his intimate scene with Debra Winger — “He’s got a Becker’s nevus!”

There’s no escaping dermatology when you’re studying for the boards!

It is fascinating to review original articles. In 1949, Becker described two young men, aged 17 and 24, respectively, with “blotchy” brown pigmentation with dark hairs, on the shoulder region, first noting their lesions in their early to mid teens. Both patients had their lesions follow an intense sunburn, allowing Dr. Becker to question if that had a role in pathogenesis. (1) (Is there any Kabbalistic meaning to the fact that Richard Gere was born in 1949?)

Becker’s nevus (BN) is a relatively common, hyperpigmented patch, frequently associated with hypertrichosis. Males are more commonly affected than females, with an incidence of around 0.25%. (2) Familial BN are rare, with autosomal dominant inheritance. (3) The common clinical presentation is multiple macules associated with hypertrichosis and hyperpigmentation in trunk or shoulder with a unilateral distribution. It can also present without hypertrichosis. Histological evaluation reveals acanthosis, epidermic hyperpigmentation, papillomatosis, arrector pili muscle hyperplasia and dermal melanophages. The Becker’s nevus syndrome (BNS) is defined by a Becker’s nevus and other skin, muscle, and/or skeletal disorders, which may include ipsilateral hypoplasia of shoulder or arm, ipsilateral breast hypoplasia, supernumerary nipple, facial asymmetry, skin hypoplasia of temporal region, spina bifida, spinal fusion, pectus carinatum or excavatum, scoliosis, lipodystrophy, stress fractures, accessory scrotum, contralateral hypoplasia of labia minora, and umbilical hernia. (4)

Treatment of BN and BNS has been suboptimal, including mechanical abrasion, surgical excision, cryotherapy, and lasers, including a combined therapy with the long-pulsed 1064nm Nd:YAG and 755nm alexandrite laser. (5) Spironolactone has improved breast hypoplasia associated with BN. (5)

The etiology of BN and BNS has been elusive. There is believed to be an increase in the number of androgen receptors in BN. (6) In an exciting development, Cai et al identified recurrent ACTB hotspot mutations in 61% (14 of 23 patients) of Becker nevi that were studied by exome sequencing. ACTB encodes for beta-actin, an intracellular cytoskeletal molecule, ubiquitously expressed with functions in cell migration, proliferation, and gene expression. BNS may due to an earlier developmental mutation, affecting multiple cell lineages compared with an isolated BN. (7) In an accompanying commentary by Rudolf Happle, it is hypothesized that these mutations may interfere with Hedgehog pathway signaling. (8)

Deciphering the postzygotic mutations in BN and BNS may lead to targeted therapies to that could minimize their phenotypic expression.

I give Richard Gere credit for having the confidence to reveal his true self on the silver screen. Perhaps in future roles he will be able to demonstrate his physique with a minimized BN following gene therapy for the beta-actin mutation.

1. Becker SW. Concurrent melanosis and hypertrichosis in distribution of nevus unius lateris. Arch Dermatol Syphilol 149; 60 155-60.
2. Sahu P, et al. Becker’s nevus associated with basal cell carcinoma: An unusual presentation in a sun-protected area. An Bras Dermatol 2017; 92: 145-7.
3. Pai VV, et al. Becker’s nevus among siblings. Indian J Dermatol, Venereol, and Leprol 2016; 82:: 359
4. Hernandez-Quiceno S, et al. Becker’s nevus syndrome in a pediatric female patient. Case Rep Pediatr 2016; 2016: 385618.
5. Wulkan AJ, et al. Successful treatment of Becker’s nevus with long-pulsed 1064nm Nd:YAG and 755nm alexandrite laser and review of the literature. J Cosmet Laser Ther 2017; May 12 [Epub ahead of print]
6. Ghosh SK, et al. Becker’s nevus syndrome; a report of a rare disease with unusual associations. Int J Dermatol 2017; 56: 458-60.
7. Cai ED, et al. Postzygotic mutations in beta-actin are associated with Becker’s nevus and Becker’s nevus syndrome. J Invest Dermatol 2017; 137: 1795-8.
8. Happle R. Becker’s nevus and lethal beta-actin mutations. J Invest Dermatol 2017; 137: 1619-21.

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