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PurposeSomatic activating variants in the PI3K-AKT pathway cause vascular malformations with and without overgrowth. We previously reported an individual with capillary and lymphatic malformation harboring a pathogenic somatic variant in PIK3R1, which encodes three PI3K complex regulatory subunits. Here, we investigate PIK3R1 in a large cohort with vascular anomalies and identify an additional 16 individuals with somatic mosaic variants in PIK3R1.MethodsAffected tissue from individuals with vascular lesions and overgrowth recruited from a multisite collaborative network was studied. Next-generation sequencing targeting coding regions of cell-signaling and cancer-associated genes was performed followed by assessment of variant pathogenicity.ResultsThe phenotypic and variant spectrum associated with somatic variation in PIK3R1 is reported herein. Variants occurred in the inter-SH2 or N-terminal SH2 domains of all three PIK3R1 protein products. Phenotypic features overlapped those of the PIK3CA-related overgrowth spectrum (PROS). These overlapping features included mixed vascular malformations, sandal toe gap deformity with macrodactyly, lymphatic malformations, venous ectasias, and overgrowth of soft tissue or bone.ConclusionSomatic PIK3R1 variants sharing attributes with cancer-associated variants cause complex vascular malformations and overgrowth. The PIK3R1-associated phenotypic spectrum overlaps with PROS. These data extend understanding of the diverse phenotypic spectrum attributable to genetic variation in the PI3K-AKT pathway.

ObjectiveTo identify risk factors associated with nonmelanoma skin cancer (NMSC) occurrence and survival in children.Study designThis was a multicenter, retrospective, case-control study of patients 12 months prior to diagnosis and 49% of patients were diagnosed with ≥2 skin cancers. At last follow-up, 5% (6 of 124) of patients with NMSC died. Voriconazole exposure was noted in 7 cases and associated with worse 3-year overall survival (P = .001).ConclusionsNMSC in children and young adults is often associated with a predisposing condition or iatrogenic exposure. High-risk patients should be identified early to provide appropriate counseling and management.

Background/Aims: Congenital melanocytic nevi (CMN) are often unexpected discoveries at time of childbirth or adoption. Understanding how parents/guardians cope with these visible birthmarks can help clinicians better care for children and their families. Using qualitative methods, we sought to categorize early family responses to CMN and identify approaches to better engage with parents early in their child's life. Methods: Semi‐structured interviews were conducted within a broader study on shared decision making for families with children with CMN. Discussions included information on birth and early life experiences. Data was dual‐coded, inductively and deductively, and analyzed with the Parker and Endler framework exploring emotion‐, task‐, and avoidance‐oriented coping. Results: Fifteen parents of 13 children were interviewed. Parents described all three categories of coping. Emotions ranged from guilt, to neutrality, to positive responses seeing their child's CMN. Stress was lower in families with prior knowledge of CMN. Dermatology referral provided an opportunity for learning, but also triggered worry for some families. Conclusions: Parents process and react to the diagnosis of CMN with a range of emotions and coping styles. Dermatologists can utilize open‐ended questions to understand family emotions and provide families with tailored knowledge and resources. Early discussion of the diagnosis and family education are important support tools. [ABSTRACT FROM AUTHOR]

The patient subsequently developed genital ulcers, and met clinical criteria for Behçet's syndrome (recurrent oral aphthous ulcers, genital ulceration, skin features). B Cutaneous ulcerations demonstrating pathergy (left), periungual lesion (middle), and an ulcerative scalp lesion (right) C-D Immunophenotyping of patient cells demonstrated C increased frequency of CD4-CD8- TCR + T cells (gated on CD3 + TCR / + cells). 1Clinical features of patient with Behçet's syndrome and STAT1 functional testing. In the largest published cohort of STAT1 GOF patients (247 patients), 98% had CMC [[1]], however other clinical symptoms can vary, even with the same variant. [Extracted from the article]

Supplemental digital content is available in the text. Background: Patch testing is the standard to diagnose allergic contact dermatitis (ACD). Objective: This study assessed the value of patch testing for product changes and quality of life in children with ACD. Methods: In this cross-sectional survey, we used a questionnaire to follow up with families of ACD patients about changes since patch testing and counseling preferences. Eligible participants were 18 years or younger during expanded series or personalized patch tests at the Washington University School of Medicine from 2007 to 2020. Results: Of the 43 enrolled participants, most were positive for multiple allergens (63%) and changed personal products after patch testing (71%). Only 26% of the families consistently read product labels before patch testing, compared with 66% after. Patients saw a mean relative reduction of 49% in severity of rash (8.2–4.2 of 10), 46% in interference with activities (5.7–3.1), and 51% in self-consciousness (7.0–3.4) since patch testing. Families gave favorable feedback for counseling on products to avoid (9.4 of 10 average rating of usefulness), product recommendations (8.5 of 10), and chemical names (7.9 of 10). Conclusions: Patch testing can lead to meaningful improvements in quality of life for most children with ACD. Counseling related to positive patch test results should include discussion of specific products to use and avoid. [ABSTRACT FROM AUTHOR]

After loss of intestinal surface area, the remaining bowel undergoes a morphometric and functional adaptive response. Enterocytic expression of the transcriptional coregulator tetradecanoyl phorbol acetate induced sequence 7 (Tis7) is markedly increased in a murine model of intestinal adaptation. Mice overexpressing Tis7 in intestine have greater triglyceride absorption and weight gain when fed a high-fat diet (42% energy) than their wild-type (WT) littermates fed the same diet. These and other data suggest that Tis7 has a unique role in nutrient absorptive and metabolic adaptation. Herein, male [Tis7.sup.-/-] and WT mice were fed a high-fat diet (42% energy) for 8 wk. Weight was monitored and metabolic analyses and hepatic and intestinal lipid concentrations were compared after 8 wk. Intestinal lipid absorption and metabolism studies and intestinal resection surgeries were performed in separate groups of [Tis7.sup.-/-] and WT mice. At 8 wk, weight gain was less and jejunal mucosal and hepatic triglyceride and cholesterol concentrations were lower in [Tis7.sup.-/-] mice than in the WT controls. Following corn oil gavage, serum cholesterol, triglyceride, and FFA concentrations were lower in the [Tis7.sup.-/-] mice than in the WT mice. Incorporation of oral [sup.3][H] triolein into intestinal mucosal cholesterol ester and FFA was less in [Tis7.sup.-/-] compared with WT mice. Following resection, crypt cell proliferation rates and villus heights were lower in [Tis7.sup.-/-] than in VVT mice, indicating a blunted adaptive response. Our results suggest a novel physiologic function for Tis7 in the gut as a global regulator of lipid absorption and metabolism and epithelial cell proliferation. J. Nutr. 140: 1907-1914, 2010. doi: 10.3945/jn.110.127084.