Human endogenous retroviruses (HERVs) are relics of ancestral infections and represent 8% of the human genome. They are no longer infectious, but their activation has been associated with several disorders, including neuropsychiatric conditions. Enhanced expression of HERV-K and HERV-H envelope genes has been found in the blood of autism spectrum disorder (ASD) patients, but no information is available on syncytin 1 (SYN1), SYN2, and multiple sclerosis-associated retrovirus (MSRV), which are thought to be implicated in brain development and immune responses. HERV activation is regulated by TRIM28 and SETDB1, which are part of the epigenetic mechanisms that organize the chromatin architecture in response to external stimuli and are involved in neural cell differentiation and brain inflammation. We assessed, through a PCR realtime Taqman amplification assay, the transcription levels of pol genes of HERV-H, -K, and -W families, of env genes of SYN1, SYN2, and MSRV, as well as of TRIM28 and SETDB1 in the blood of 33 ASD children (28 males, median 3.8 years, 25–75% interquartile range 3.0–6.0 y) and healthy controls (HC). Significantly higher expressions of TRIM28 and SETDB1, as well as of all the HERV genes tested, except for HERV-W-pol, were found in ASD, as compared with HC. Positive correlations were observed between the mRNA levels of TRIM28 or SETDB1 and every HERV gene in ASD patients, but not in HC. Overexpression of TRIM28/SETDB1 and several HERVs in children with ASD and the positive correlations between their transcriptional levels suggest that these may be main players in pathogenetic mechanisms leading to ASD.

Autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED), caused by mutations in the AIRE gene, is mainly characterized by the triad of hypoparathyroidism, primary adrenocortical insufficiency and chronic mucocutaneous candidiasis, but can include many other manifestations, with no currently clear genotype–phenotype correlation. We present the clinical features of two siblings, a male and a female, with the same mutations in the AIRE gene associated with two very different phenotypes. Interestingly, the brother recently experienced COVID-19 infection with pneumonia, complicated by hypertension, hypokalemia and hypercalcemia. Although APECED is a monogenic disease, its expressiveness can be extremely different. In addition to the genetic basis, epigenetic and environmental factors might influence the phenotypic expression, although their exact role remains to be elucidated.

Children with multisystem inflammatory syndrome (MIS-C) tend to develop a clinical condition of fluid overload due both to contractile cardiac pump deficit and to endotheliitis with subsequent capillary leak syndrome. In this context, the ability of point-of-care ultrasound (PoCUS) to simultaneously explore multiple systems and detect polyserositis could promote adequate therapeutic management of fluid balance. We describe the PoCUS findings in a case-series of MIS-C patients admitted to the Emergency Department. At admission 10/11 patients showed satisfactory clinical condition without signs and symptoms suggestive for cardiovascular impairment/shock, but PoCUS showed pathological findings in 11/11 (100%). In particular, according to Rapid Ultrasound in SHock (RUSH) protocol, cardiac hypokinesis was detected in 5/11 (45%) and inferior vena cava dilatation in 3/11 (27%). Peritoneal fluid was reported in 6/11 cases (54%). Lung ultrasound (LUS) evaluation revealed an interstitial syndrome in 11/11 (100%), mainly localized in posterior basal lung segments. We suggest PoCUS as a useful tool in the first evaluation of children with suspected MIS-C for the initial therapeutic management and the following monitoring of possible cardiovascular deterioration.

: Introduction and importance: Rhabdomyosarcoma is the most common pediatric soft tissue sarcoma. It constitutes 4 – 6% of all malignancies in childhood. The botryoid variant is a type of ERMS that is the most common malignancy in the pediatric female genitourinary tract. ERMS of the vagina usually occurs in early childhood, whereas ERMS of the uterus occurs later in age. Since 1959, only 7 cases of uterine botryoid ERMS during infancy have been reported. Case presentation: A 15-months-old girl was admitted to our ED for three reddish, smooth, glistening, polypoidal masses protruding from her vaginal introitus for 9 days. The lesions had a suspicious “grape-like” appearance and tended to come in and out through the vaginal ostium. A pelvic US examination on the patient showed an inhomogeneous aspect of the uterus, which appeared to be occupied and stretched out by an iso-hypoechogenic solid tissue. Additionally, there were some hyperechogenic spots inside as well as evidence of vascular signals on color doppler. A surgical biopsy revealed a malignant mesenchymal tumor consistent with the diagnosis of embryonal rhabdomyosarcoma (ERMS), botryoid variant. Clinical Discussion: The patient completed her first cycle of chemotherapy with ifosfamide, vincristine, and dactinomycin (IVA). When she was 18 months old, she underwent a hysterectomy, which removed the entire mass with a Pfannenstiel approach. The postoperative course presented with no complications. Follow-up visits were scheduled quarterly. Conclusion: Botryoid ERMS of the uterus is a diagnosis not to be missed in an infant. Since rapid diagnosis and treatment are necessary, clinicians should be aware of its presentation to assure optimal management. Highlights:

Multisystem inflammatory syndrome related to SARS-CoV-2 infection (MIS-C) is a rare severe illness affecting pediatric patients. No data are available in literature about the presence of SARS-CoV-2 RNA in faeces in patients with MIS-C. The SARS-CoV-2 positivity was evaluated in fecal samples obtained in a prospective cohort of pediatric patients admitted to our tertiary Hos-pital and diagnosed with MIS-C or COVID-19 between April 15, 2020, and February 29, 2021. The real-time RT-PCR was performed using a validated kit. The assay measures 3 target genes: SARS-CoV-2 gene E, gene N, gene ORF1ab. Overall, 16/63 (25%) fecal samples revealed the pres-ence of SARS -CoV-2 RNA. No differences were detected about time from presumptive viral ex-posure and the time of stool collection (14 vs 8 days, p> 0,05) as well as about the presence of gas-trointestinal symptoms (p>0.05) between patients with positive (+) stools for SARS-CoV-2 RNA and patients tested negative (-). Among children with MIS-C, stools were collected 27.5 days as median (95% CI 14-34) after presumed contact and the positivity rate was 12.5% (4/32). According to our data, we could suggest contact precautions with all patients with MIS-C. Further sample collection is ongoing to verify our preliminary data.