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A challenge of early adolescence is the “developmental mismatch” between adolescents’ need for autonomy and the lack of opportunities to enact maturity via adult-like roles. We identified ways that...

This serves as the preregistration of the Stage 1 accepted manuscript

Stage 1 Registered Report. During adolescence, increases in pubertal hormones lead to reproductive maturity and drive changes in cognitive development. However, little is known about how to best characterize interindividual differences in hormone concentrations. The goal of the proposed study is to examine the antecedents and consequences of membership in empirically derived hormone subgroups. Data will be drawn from over 11,000 youth (approximately 50% male, ages = 9 -11 years) from the Adolescent Brain Cognitive Development study.Latent profile analysis stratified by sex will be used to derive profiles of hormone exposure based on basal testosterone, dehydroepiandrosterone (DHEA), and estradiol (girls only). Profile membership will then be related to pubertal status, race/ethnicity, socioeconomic status, and body mass index (BMI). Additionally, profile membership will be examined as a prospective predictor of adolescents’ cognition (i.e., inhibitory control, visuospatial processing, decision-making) assessed two years later. Findings will clarify disparate associations between hormones and behavior in adolescence and underscore the importance for youth-centered approaches that focus on patterns of individual characteristics.

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At one time considered opposing diseases, it is now recognized that atopic dermatitis (AD) and psoriasis can coexist. There are limited data characterizing this population of patients. In this study, we characterize the population of patients diagnosed with both AD and psoriasis and summarize their response to therapy.A retrospective chart review was performed and data was recorded for patients with a diagnosis of psoriasis (The prevalence of concomitant AD and psoriasis was 1.5%. Of those with both AD and psoriasis, hand involvement was high (63%). Systemic therapy was used in 73% of patients. Of those on biologics, 30% required more than one biologic consecutively and 22% required more than one biologic simultaneously to achieve clinically significant results.Patients with overlapping AD and psoriasis have a high prevalence of hand involvement, poor response to topical therapy, and may require multiple systemic agents to treat. In a patient with known history of psoriasis with recalcitrant hand disease involvement, AD should be considered.

Executive functioning (EF) is fundamental to positive development. Yet, little is known about how to best characterize constellations of EF skills that may inform disparate associations between EF and behavior during adolescence. In the current study, cross-validated latent profile analysis (LPA) was used to derive profiles of EF based on measures of inhibitory control, working memory, and cognitive flexibility using data from 11,672 youth (52.2% male, mean age = 9.91 years) in the Adolescent Brain and Cognitive Development study. Four meaningful EF profiles emerged from the data representing Average EF, High EF, Low Inhibitory Control, and Low EF. Boys, youth from low-income households, and early developing youth were more likely to be in profiles distinguished by lower EF. Profile membership also predicted differences in externalizing, internalizing, and other problem behaviors assessed one year later. Findings indicate that youth may have distinct constellations of EF skills, underscoring the need for person-centered approaches that focus on patterns of individual characteristics.

Background: Disorders of somatic mosaicism (DoSM) are caused by mutations that arise post-zygotically and are present in only a specific part of the body. These mutations alter the function and regulation of key genes in cell proliferation pathways, including the PI3K/AKT/mTOR pathway, and show significant overlap with mutations identified in cancer(McNulty et al. Am J Hum Genet, 2019). PIK3CA-Related Overgrowth Spectrum (PROS) is an umbrella term that encompasses a variety of overgrowth syndromes caused by post-zygotic, somatic gain-of-function PIK3CA mutations with low-level mosaicism (Luks et al. J Pediatr, 2015). The clinical phenotype of PROS is heterogeneous and many tissue types can be affected. This often makes clinical diagnosis challenging. The use of cancer genomics in patients with vascular anomalies may aid in establishing a genetic diagnosis and expand use of targeted medical therapies. Methods: Three patients who presented with clinical symptoms of PROS underwent targeted next generation sequencing of affected tissue using OncoPanel. Oncopanel is a genomic assay that detects somatic mutations, copy number variations and structural variants in 447 genes implicated in cancer. Results: Three patients with a PROS phenotype demonstrated somatic mutations in genes distinct from PIK3CA. Case 1: A 15-year-old female presented with a painful right leg mass, calf atrophy, contracture of the knee, leg-length discrepancy, and severe limp. Histology was consistent with fibroadipose vascular anomaly (FAVA) versus kaposiform hemangioendothelioma (KHE). Given her significant functional impairment, treatment with Sirolimus was initiated with significant improvement in appearance and functionality. OncoPanel testing revealed a PIK3C2B c.2881G>A (p.G961S) mutation. Case 2: A 12-month-old male was noted at birth to have a diffuse capillary malformation, multiple lymphatic malformations, macrodactyly of his bilateral hands and leg length-discrepancy, consistent with Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevi, Spinal/Skeletal Anomalies/Scoliosis (CLOVES) syndrome. He underwent numerous surgical de-bulking procedures, epiphysiodesis, sclerotherapy, and laser therapy with continued disease progression. OncoPanel revealed a PIK3R1c.1731_1738delAGACCAATinsATGTAAGAAAG (p.D578_Y580delinsCKKD) mutation. Case 3: A 10-month-old female presented with a diffuse capillary malformation and leg-length discrepancy. She subsequently developed multiple painful and progressive lymphatic lesions over her left arm and chest which did not respond to sclerotherapy. Due to high clinical suspicion for PROS, she underwent targeted genetic testing via droplet digital PCR (ddPCR) to detect the five most common variants (C420R, E542K, E545K, H1047L, H1047R) in PIK3CA, but no hotspot mutations were identified. Over the next year and a half, the patient had two biopsies performed, PIK3CA ddPCR testing performed twice, and OncoPanel testing performed twice. OncoPanel testing of the second tissue biopsy ultimately resulted in the identification of a PIK3R1 c.1723-1731del p.K575_R577del mutation. Conclusion: The clinical diagnosis of DoSM is often challenging. While the use of cancer genomics for diagnostic purposes in vascular anomalies is uncommon, its use continues to broaden our understanding of syndromes related to alterations in the PI3K/AKT/mTOR pathway. PIK3CB encodes a catalytic subunit of PI3K, p110β, and is dysregulated in certain types of cancer. PIK3R1 encodes multiple regulatory subunits of PI3K and acts as a negative regulator of PIK3CA function. Both gain-of-function of PIK3CB or loss-of-function of PIK3R1 lead to inappropriate activation of PIK3CA, and our cases highlight that mutations in other genes can lead to the clinical phenotype of PROS. It is reasonable to expect that patients with alterations in genes that activate PIK3CA may benefit from medical treatment with direct PIK3CA inhibitors. Limiting diagnostic testing to evaluation of the PIK3CA gene alone may yield negative results and preclude patient eligibility for treatment with novel therapies. The use of next-generation sequencing (NGS) designed to detect somatic variations in cancer will likely play a pivotal role in detecting variants in vascular anomalies in the future and in expanding our understanding of genetic alterations involved in PROS. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Sirolimus is used off-label for the treatment of vascular anomalies.

The current study investigated patterns in executive functioning (EF) skills in adolescents (N = 991; 48.8% male; 81% White; mage = 14.91) and examined how EF profiles were associated with adolescent wellbeing. Eight EF skills, comprising foundational, complex, and affective EF, were assessed via self-rated EF, parent-reported EF, and neuropsychological tasks. A latent profile analysis (LPA) revealed four distinct EF profiles representing unique constellations of higher, lower, or mixed performance across all eight EF skills. When compared across domains, profiles characterized by higher foundational and complex EF skills exhibited positive, contemporaneous associations with academics, mental health, and health behaviors. Profiles characterized by discordant or mixed performance also exhibited unique strengths, such as positive peer relationships. Findings indicate that person-centered approaches to examining EF may reveal important sources of heterogeneity that have functional significance for health and wellness.