A very mild phenotype in six individuals of a three-generation family with the novel HRAS variant c.176C > G p.(Ala59Gly): Emergence of a new HRAS-related RASopathy distinct from Costello syndrome

Costello syndrome is a clinically recognizable, severe neurodevelopmental disorder caused by heterozygous activating variants in HRAS. The vast majority of affected patients share recurring variants affecting HRAS codons 12 and 13 and a relatively uniform phenotype. Here, we report the unique and attenuated phenotype of six individuals of an extended family affected by the HRAS variant c.176C>T p.(Ala59Gly), which, to our knowledge, has never been reported as a germline variant in patients so far. HRAS Alanine 59 has been previously functionally investigated as an oncogenic hotspot and the p.Ala59Gly substitution was shown to impair intrinsic GTP hydrolysis. All six individuals we report share a phenotype of ectodermal anomalies and mild features suggestive of a RASopathy, reminiscent of patients with Noonan syndrome-like disorder with loose anagen hair. All six are of normal intelligence, none have a history of failure to thrive or malignancy, and they have no known cardiac or neurologic pathologies. Our report adds to the previous reports of patients with rare variants affecting amino acids located in the SWITCH II/G3 region of HRAS and suggests a consistent, attenuated phenotype distinct from classical Costello syndrome. We propose the definition of a new distinct HRAS-related RASopathy for patients carrying HRAS variants affecting codons 58, 59, 60

Tinea genitalis: a new entity of sexually transmitted infection? Case series and review of the literature

OBJECTIVE Investigation on recent cases of tinea genitalis after travelling to South East Asia. METHODS Patients with tinea in the genital region, which emerged after sex in South East Asia, underwent further assessment including microscopy, cultures and DNA analyses. RESULTS The case series includes seven patients. In six patients, Trichophyton interdigitale (former Trichophyton mentagrophytes) was detected. Three patients suffered from a severe inflammatory reaction of the soft tissue and two of them needed hospitalisation due to severe pain. In four patients, cicatrising healing was noticed. Five patients were declared incapacitated for work. CONCLUSIONS Sexual activity should be considered as a potentially important and previously underappreciated means of transmission of T. interdigitale. To avoid irreversible scarring alopecia, prompt initiation of antifungal treatment is essential and adequate isolation and identification of the pathogen is mandatory

Clinical characteristics and serological profiles of Lyme disease in children: a 15-year retrospective cohort study in Switzerland

BACKGROUND Lyme disease (LD) is caused by Borrelia burgdorferi and is the most common tickborne disease in the northern hemisphere. Although classical characteristics of LD are well-known, the diagnosis and treatment are often delayed. Laboratory diagnosis by serological testing is recommended for most LD manifestations. The objective of this study was to describe clinical characteristics and associated serological profiles in children with LD. METHODS This retrospective cohort study included children aged 0-18 years, diagnosed with LD according to current guidelines at University Children's Hospital Zurich between January 1, 2006 and December 31, 2020. Two-tier serological testing with the recomWell enzyme-linked immunosorbent assay and recomLine Western blot (MIKROGEN Diagnostik, MIKROGEN GmbH, Neuried, Germany) was performed at the Institute of Medical Microbiology, University of Zurich. FINDINGS In total, 469 children diagnosed with LD were included (median age, 7.9 years); 190 patients (40.5%) with Lyme neuroborreliosis (LNB), 171 (36.5%) patients with skin manifestations (erythema migrans, n = 121; multiple erythema migrans, n = 11; borrelial lymphocytoma, n = 37; and acrodermatitis chronica atrophicans, n = 2), and 108 (23.0%) patients with Lyme arthritis. We observed seasonal variations for patients with skin manifestations and LNB, with high prevalence in May-October, but not for patients with Lyme arthritis. Significant differences between LD manifestation groups were found for age, inflammatory parameters, and specificity and concentration of B. burgdorferi-specific serum antibody responses. We observed distinct patterns of pronounced serum antibody responses against B. burgdorferi antigens in LNB (IgM against VlsE, p41, and OspC) and Lyme arthritis (IgG against p100, VlsE, p58, p41, p39, and p18). INTERPRETATION Our study is one of the largest and most detailed for children with LD. We present unique findings regarding the differences in clinical characteristics and immune responses between various manifestations of LD in children. FUNDING No specific funding to disclose for this study