ORIGINAL RESEARCH ARTICLEPurpose: Mowat-Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype-phenotype correlations of MWS. Methods:In a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neurodevelopmental milestones, and compared the data with the various types of underlying ZEB2 pathogenic variations.Results: All anthropometric, somatic, and behavioral features reported here outline a variable but highly consistent phenotype. By presenting the most comprehensive evaluation of MWS to date, we define its clinical evolution occurring with age and derive suggestions for patient management. Furthermore, we observe that its severity correlates with the kind of ZEB2 variation involved, ranging from ZEB2 locus deletions, associated with severe phenotypes, to rare nonmissense intragenic mutations predicted to preserve some ZEB2 protein functionality, accompanying milder clinical presentations. Conclusion:Knowledge of the phenotypic spectrum of MWS and its correlation with the genotype will improve its detection rate and the prediction of its features, thus improving patient care.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of the coronavirus disease 2019 (COVID-19) pandemic. Besides virus intrinsic characteristics, the host genetic makeup is predicted to account for the extreme clinical heterogeneity of the disease, which is characterized, among other manifestations, by a derangement of hemostasis associated with thromboembolic events. To date, large-scale studies confirmed that genetic predisposition plays a role in COVID-19 severity, pinpointing several susceptibility genes, often characterized by immunologic functions. With these premises, we performed an association study of common variants in 32 hemostatic genes with COVID-19 severity. We investigated 49,845 single-nucleotide polymorphism in a cohort of 332 Italian severe COVID-19 patients and 1668 controls from the general population. The study was conducted engaging a class of students attending the second year of the MEDTEC school (a six-year program, held in collaboration between Humanitas University and the Politecnico of Milan, allowing students to gain an MD in Medicine and a Bachelor’s Degree in Biomedical Engineering). Thanks to their willingness to participate in the fight against the pandemic, we evidenced several suggestive hits (p < 0.001), involving the PROC, MTHFR, MTR, ADAMTS13, and THBS2 genes (top signal in PROC: chr2:127192625:G:A, OR = 2.23, 95%CI = 1.50–3.34, p = 8.77 × 10−5). The top signals in PROC, MTHFR, MTR, ADAMTS13 were instrumental for the construction of a polygenic risk score, whose distribution was significantly different between cases and controls (p = 1.62 × 10−8 for difference in median levels). Finally, a meta-analysis performed using data from the Regeneron database confirmed the contribution of the MTHFR variant chr1:11753033:G:A to the predisposition to severe COVID-19 (pooled OR = 1.21, 95%CI = 1.09–1.33, p = 4.34 × 10−14 in the weighted analysis).

Background Nipple adenoma is a very uncommon, benign neoplasm that involves the nipple. A palpable mass of the nipple associated with nipple discharge and erosion or ulceration is the common clinical presentation. Generally, complete surgical excision of the nipple is the main treatment, alternative therapeutic methods such as Mohs micrographic surgery, nipple splitting enucleation, and cryotherapy can be considered. Disorders of the breast in young women are generally benign. Even if the management during pregnancy is usually conservative and surgical excision is reserved for very strong malignancy suspicion, benign lesions can cause the impossibility to breastfeed after giving birth when involving the nipple. Case presentation We present the case of a 28-year-old female, who was referred to the Breast Unit of the University Hospital of Modena (Italy) in May 2020 with a 12-months history of enlargement of the left nipple with associated erythema, serohemorrhagic discharge, and pain in the left nipple region. The diagnostic assessment came out in favor of a nipple adenoma. After surgical treatment was recommended, the patient got pregnant. Taking into account the major risks of surgery during pregnancy, a multidisciplinary discussion was conducted, to consider whether to proceed with surgery or postpone it after pregnancy. Because of the volume and the position of the adenoma, the indication for surgical excision was confirmed, to allow regular lactation and breastfeeding immediately after giving birth and to avoid potential obstructive complications. Surgical excision of nipple adenoma without complete resection of the nipple was performed after her first trimester of pregnancy under local anesthesia. A histopathological examination confirmed the diagnosis. No recurrence occurred after 12 months. The patient gave birth, had no deficit in lactation, and successfully breastfed. Conclusions Therefore, we consider that nipple adenoma enucleation might be a safe treatment even during pregnancy. Moreover, conservative local treatment of nipple adenomas can preserve the nipple aesthetically and functionally, thus allowing regular lactation and breastfeeding in young women.