A number sign (#) is used with this entry because of evidence that congenital smooth muscle hamartoma (CSMH) with or without hemihypertrophy is caused by postzygotic mutation, resulting in somatic mosaicism, in the ACTB gene (102630) on chromosome 7p22.

A related disorder, Becker nevus syndrome (BNS; 604919), shares clinical and histologic features and is also caused by somatic mutation in the ACTB gene.

Congenital smooth muscle hamartoma (CSMH) is a benign skin lesion that presents as an indurated, slightly pigmented or flesh-colored plaque with perifollicular papules or coarse hair. Histopathologically, there is excessive proliferation of ectopic smooth muscle within the dermis. Rarely, CSMH is associated with hemihypertrophy (Atzmony et al., 2020).

Atzmony et al. (2020) reported a 2-year-old boy (MOS1) with hemihypertrichosis and hemihypertrophy and postzygotic mutation in the ACTB gene. Examination revealed right-sided hypertrichosis of the upper back and posterior right arm, as well as hemihypertrophy of the right upper extremity. Biopsy of the right upper arm showed increased numbers of small bundles of smooth muscle fibers in the dermis, some associated with hair follicles and some in between hair follicles. The authors diagnosed the boy with giant segmental congenital smooth muscle hamartoma (CSMH) and hemihypertrophy, noting that the large area of CSMH involvement along with the hemihypertrophy suggested a multilineage mesodermal mosaicism.

The identification by Atzmony et al. (2020) of mutation in the ACTB gene in fibroblasts from affected skin from patients with CSMH, but not in keratinocytes from the same lesion or in patient saliva, was consistent with somatic mosaicism.

CSMH occurs in approximately 1 in 2,600 live births (summary by Atzmony et al., 2020).

In fibroblasts cultured from affected skin of a 2-year-old boy (MOS1) with segmental congenital smooth muscle hamartoma and hemihypertrophy, Atzmony et al. (2020) sequenced the ACTB gene and identified a previously reported postzygotic missense mutation, R147S, which was not found in keratinocytes from the same lesion or in patient saliva. The authors analyzed another 12 CSMH samples and identified somatic hotspot mutations in the ACTB gene in 8 samples, including the previously reported R147S mutation and recurrent mutations at residue G146: G146A (102630.0013), G146V (102630.0014), G146D (102630.0015), and G146S (102630.0016). The authors suggested that dissimilarities between Becker nevi and CSMHs might be determined by intrauterine environmental factors, mutation lineage or timing, and/or modifier genes, and that hypertrophy versus hypoplasia could be explained by different cell lineages being involved.