Recurrent Erythema Nodosum in a Child with a <i>SHOC2</i> Gene Mutation

Abstract

We report the case of a 6-year-old male who developed recurrent erythema nodosum (EN) at the age of 3 years. The patient exhibited hypertelorism, low-set ears, micrognathia, moderate intellectual disability, thin long fingers, loose anagen hair, and prominent palmoplantar wrinkles. A heterozygous single nucleotide variant in the SHOC2 gene (c.4 A > G, p.S2G) was identified. Patients with a SHOC2 mutation exhibit a unique combination of ectodermal abnormalities including darkly pigmented skin and loose anagen hair. This report is the first to describe EN in a patient with SHOC2 mutation, and to examine the patient's hair using scanning electron microscopy. We hypothesize that the RAS/MAPK pathway is associated with the pathogenesis of cutaneous lesions in patients with SHOC2 mutations via autoinflammation and disturbance of epithelial stem cells.

Cutaneous T-cell lymphoma in SHOC2 mutation-associated Noonan-like syndrome with loose anagen hair

“…The SHOC2 gene affects proliferation, survival, and differentiation of epithelial stem cell-derived cells in hair follicles; however, the relationship between SHOC2 mutations and the other cutaneous pathologies seen specifically in NS/LAH remains unclear. 7 Increased signaling through RAS/MAPK contributes to oncogenesis, and solid tumors and hematologic malignancies are described in many of the RASopathies. 8 Patients with Costello syndrome can develop rhabdomyosarcoma, ganglioneuroblastoma, and bladder carcinoma.…”

ADA2 deficiency in a patient with Noonan syndrome‐like disorder with loose anagen hair: The co‐occurrence of two rare syndromes

“…In our patient's brain imaging findings, although the third and lateral ventricles dilatation and focal cortical anomaly in the right cerebellar hemisphere were reported previously, ectopic neurohypophysis was a novel finding. Autoimmune disorders including systemic lupus erythematosus (SLE) and erythema nodosum have been reported among patients among RASopathies, especially in SHOC2 pathogenic variants (Alanay, Balci, & Ozen, 2004;Okazaki et al, 2019;Simsek-Kiper et al, 2013;Uehara, Hosogaya, Matsuo, & Kosaki, 2018). However, although the underlying mechanism cannot be fully explained, it is suggested that this coexistence of such autoinflammatory diseases with RAsopathy in multiple patients is not random (Okazaki et al, 2019;Uehara et al, 2018).…”