A number sign (#) is used with this entry because of evidence that Becker nevus syndrome (BNS) is caused by postzygotic mutation, resulting in somatic mosaicism, in the ACTB gene (102630) on chromosome 7p22.

A related disorder, congenital smooth muscle hamartoma with or without hemihypertrophy (CSMH; 620470), shares clinical and histologic features and is also caused by somatic mutation in the ACTB gene.

Becker nevus (BN) is a cutaneous hamartoma affecting approximately 1 in 200 individuals that appears in childhood as a unilateral tan patch, and increases in thickness, pigmentation, and hair growth during adolescence. Histologically, epidermal acanthosis is accompanied by irregularly dispersed ectopic smooth muscle bundles and increased terminal hair follicles (summary by Cai et al., 2017). Becker nevus syndrome (BNS) is a phenotype characterized by the presence of a Becker nevus in association with unilateral hypoplasia of breast or other cutaneous, muscular, or skeletal defects (Happle and Koopman, 1997).

Happle and Koopman (1997) reviewed 23 cases of a syndrome characterized by the presence of a Becker nevus in association with unilateral hypoplasia of breast or other cutaneous, muscular, or skeletal defects, all of which usually involve the same side of the body as the nevus. Histopathologic examination showed that the epidermal component of the nevus consisted of slight acanthosis and hyperpigmentation of basal cells, while the dermal component consisted of numerous bundles of smooth muscle fibers unrelated to hair follicles. Because the nevus is androgen-dependent, it is much less conspicuous in women and prepubertal boys. Other cutaneous anomalies included extensive patchy hypoplasia of ipsilateral subcutaneous fatty tissue, hypoplasia of contralateral labium minus, and ipsilateral accessory scrotum. Eleven of the 16 female patients had ipsilateral hypoplasia of breast. Ipsilateral hypoplasia of the shoulder girdle or absence of the pectoralis major muscle and ipsilateral shortness of the arm were observed. Skeletal anomalies included hemivertebrae or spina bifida occulta, fused or accessory cervical ribs, pectus excavatum, pectus carinatum, and internal tibial torsion. Scoliosis occurred in 28%. The male-to-female ratio was 1:2, but Happle and Koopman (1997) suggested that with more thorough clinical studies the true ratio would probably be 1:1. All cases have been sporadic. Happle (1995) proposed that the phenotype results from loss of heterozygosity for the underlying allele and is hence another example of paradominant inheritance.

Cai et al. (2017) reported a 13-year-old girl with Becker nevus syndrome and postzygotic mutation in the ACTB gene. She presented with hyperpigmented patches overlying her arms, legs, torso, and back, and also exhibited unilateral left breast and pectoralis muscle hypoplasia. Lesional skin biopsy showed epidermal acanthosis with flat-tipped rete ridges, basilar hyperpigmentation, and smooth muscle hypertrophy.

Ramspacher et al. (2022) reported a 17-year-old French girl with Becker nevus syndrome and postzygotic mutation in the ACTB gene. She presented at age 11 years with a light brown hyperpigmented skin lesion on the left hemithorax, extending from the area of the breast to the axilla. She had severe left breast hypoplasia, and ultrasound revealed a hypoplastic left mammary bud.

The identification of heterozygous mutations in the ACTB gene in Becker nevi, but not in adjacent normal skin, indicated somatic mosaicism. Identification of mutation in pilar muscle from syndromic and nonsyndromic Becker nevi, but not in epidermis or stroma, was consistent with the presence of the mutations in mesenchymal lineage (Cai et al., 2017).

In a 13-year-old girl with Becker nevus syndrome, Cai et al. (2017) performed exome sequencing of affected and nonaffected skin and identified heterozygosity for a missense mutation in the ACTB gene (R147C; 102630.0011) in lesional skin that was absent from adjacent normal skin. Analysis of 22 nonsyndromic Becker nevi revealed that 13 contained a hotspot point mutation involving the same codon, including 10 with the R147C substitution and 3 with an R147S substitution (102630.0012). Laser-capture microdissection to isolate DNA from epidermis, stroma, and pilar muscles in 1 syndromic and 2 nonsyndromic Becker nevi revealed that in all 3 cases, the ACTB mutation was present only in pilar muscle, with an average allele frequency of 22%. Functional analysis in transfected C2C12 myoblast cells suggested a trend towards increased Hedgehog (see 600726) pathway signaling. The authors hypothesized that Becker nevus-associated ACTB mutations act in a non-cell autonomous manner, since mutations were identified only in pilar muscle but the clinical phenotype involves hyperplasia of epidermis and hair follicles. They also suggested that Becker nevus syndrome may reflect a mutation earlier in development, affecting multiple cell lineages, compared with isolated Becker nevus.

Using DNA from a biopsy of affected skin from a 17-year-old French girl with Becker nevus syndrome, Ramspacher et al. (2022) sequenced the ACTB gene and identified heterozygosity for the previously reported postzygotic missense mutation R147C.