Dawn H. Siegel, MD

All Publications

• Presenting characteristics and progression of pediatric-onset morphea: Interim analysis of a prospective registry. Pediatric dermatology Ng, A. T., Brandling-Bennett, H. A., Drolet, B. A., Siegel, D. H., Chiu, Y. E. 2023

  Abstract

  Morphea is a rare fibrosing disorder with a highly variable disease course, which can complicate management. Here, we present a prospective cohort study describing the current treatments used in the management of pediatric-onset morphea and assessing responses to systemic and topical therapies. Most patients demonstrated inactive disease by 1 year, regardless of treatment, though recurrences were common in our cohort overall (39%). Our results support the need for continuous monitoring of all children with morphea following the completion of treatment, including topical treatment, due to high rates of disease relapse.

  View details for DOI 10.1111/pde.15350

  View details for PubMedID 37317938

• PTPN11 Mosaicism Causes a Spectrum of Pigmentary and Vascular Neurocutaneous Disorders and Predisposes to Melanoma JOURNAL OF INVESTIGATIVE DERMATOLOGY Polubothu, S., Bender, N., Muthiah, S., Zecchin, D., Demetriou, C., Martin, S., Malhotra, S., Travnickova, J., Zeng, Z., Boehm, M., Barbarot, S., Cottrell, C., Davies, O., Baselga, E., Burrows, N. P., Carmignac, V., Diaz, J., Fink, C., Haenssle, H. A., Happle, R., Harland, M., Majerowski, J., Vabres, P., Vincent, M., Newton-Bishop, J. A., Bishop, D., Siegel, D., Patton, E., Topf, M., Rajan, N., Drolet, B., Kinsler, V. A. 2023; 143 (6): 1042-1051.e3

  Abstract

  Phakomatosis pigmentovascularis is a diagnosis that denotes the coexistence of pigmentary and vascular birthmarks of specific types, accompanied by variable multisystem involvement, including CNS disease, asymmetrical growth, and a predisposition to malignancy. Using a tight phenotypic group and high-depth next-generation sequencing of affected tissues, we discover here clonal mosaic variants in gene PTPN11 encoding SHP2 phosphatase as a cause of phakomatosis pigmentovascularis type III or spilorosea. Within an individual, the same variant is found in distinct pigmentary and vascular birthmarks and is undetectable in blood. We go on to show that the same variants can cause either the pigmentary or vascular phenotypes alone, and drive melanoma development within pigmentary lesions. Protein structure modeling highlights that although variants lead to loss of function at the level of the phosphatase domain, resultant conformational changes promote longer ligand binding. In vitro modeling of the missense variants confirms downstream MAPK pathway overactivation and widespread disruption of human endothelial cell angiogenesis. Importantly, patients with PTPN11 mosaicism theoretically risk passing on the variant to their children as the germline RASopathy Noonan syndrome with lentigines. These findings improve our understanding of the pathogenesis and biology of nevus spilus and capillary malformation syndromes, paving the way for better clinical management.

  View details for DOI 10.1016/j.jid.2022.09.661

  View details for Web of Science ID 001010699700001

  View details for PubMedID 36566878

• Papillomas of Costello syndrome are not associated with human papillomavirus (HPV) infection in a small case series. Journal of the American Academy of Dermatology Olsen, G. M., Johnson, L., Castel, P., Stevenson, D. A., White, K., Chiu, Y. E., Krol, A., Siegel, D. H. 2023

  View details for DOI 10.1016/j.jaad.2023.03.043

  View details for PubMedID 37028601

• Two for two: Dual therapy with erlotinib and acitretin for twins with severe keratoderma in Olmsted syndrome. Pediatric dermatology Butala, S., Phan, S., Siegel, D. H., Carlberg, V., Paller, A. S. 2023

  Abstract

  Olmsted syndrome (OS) is a rare genetic disorder, characterized by painful palmoplantar keratoderma (PPK), periorificial and intertriginous hyperkeratoses, and alopecia. Fewer than 75 cases have been described. Variants in TRPV3 result in constitutive activation of transient receptor potential vanilloid 3, leading to increased epidermal growth factor receptor (EGFR) signaling, palmoplantar epidermal hyperproliferation, and exquisite lesional pain. We describe pre-school aged twins with OS with partial improvement from oral erlotinib, an EGFR inhibitor, but dramatic reduction of their persistent palmoplantar thickening and pain from adding acitretin.

  View details for DOI 10.1111/pde.15264

  View details for PubMedID 36709954

• Early-onset hypertension associated with extensive cutaneous capillary malformations harboring postzygotic variants in GNAQ and GNA11. Pediatric dermatology Davies, O. M., Ng, A. T., Tran, J., Blumenthal, S., Arkin, L. M., Nopper, A. J., Cottrell, C. E., Garzon, M., Siegel, D. H., Frieden, I. J., Drolet, B. A. 2022; 39 (6): 914-919

  Abstract

  Cutaneous capillary malformations (CMs) describe a group of vascular birthmarks with heterogeneous presentations. CMs may present as an isolated finding or with other associations, including glaucoma and leptomeningeal angiomatosis (i.e., Sturge-Weber syndrome) or pigmentary birthmarks (i.e., phakomatosis pigmentovascularis). The use of targeted genetic sequencing has revealed that postzygotic somatic variations in GNAQ and GNA11 at codon 183 are associated with CMs. We report five patients with early-onset hypertension and discuss possible pathogenesis of hypertension.Twenty-nine patients with CMs, confirmed GNAQ/11 postzygotic variants, and documented past medical history were identified from a multi-institutional vascular anomalies study. Early-onset hypertension was defined as hypertension before the age of 55 years. Clinical data were reviewed for evidence of hypertension, such as documentation of diagnosis or elevated blood pressure measurements.Five of the 29 patients identified as having GNAQ/11 postzygotic variants had documented early-onset hypertension. Three individuals harbored a GNAQ p.R183Q variant, and two individuals harbored a GNA11 p.R183C variant. All individuals had extensive cutaneous CMs involving the trunk and covering 9%-56% of their body surface area. The median age of hypertension diagnosis was 15 years (range 11-24 years), with three individuals having renal abnormalities on imaging.Early-onset hypertension is associated with extensive CMs harboring somatic variations in GNAQ/11. Here, we expand on the GNAQ/11 phenotype and hypothesize potential mechanisms driving hypertension. We recommend serial blood pressure measurements in patients with extensive CMs on the trunk and extremities to screen for early-onset hypertension.

  View details for DOI 10.1111/pde.15103

  View details for PubMedID 36440997

• Development of an artificial intelligence algorithm for the diagnosis of infantile hemangiomas. Pediatric dermatology Zhang, A. J., Lindberg, N., Chamlin, S. L., Haggstrom, A. N., Mancini, A. J., Siegel, D. H., Drolet, B. A. 2022

  Abstract

  Prompt and accurate diagnosis of infantile hemangiomas is essential to prevent potential complications. This can be difficult due to high rates of misdiagnosis and poor access to pediatric dermatologists. In this study, we trained an artificial intelligence algorithm to diagnose infantile hemangiomas based on clinical images. Our algorithm achieved a 91.7% overall accuracy in the diagnosis of facial infantile hemangiomas.

  View details for DOI 10.1111/pde.15149

  View details for PubMedID 36164801

• Early-onset hypertension associated with extensive cutaneous capillary malformations harboring postzygotic variants in GNAQ and GNA11 PEDIATRIC DERMATOLOGY Davies, O. T., Ng, A. T., Tran, J., Blumenthal, S., Arkin, L. M., Nopper, A. J., Cottrell, C. E., Garzon, M., Siegel, D. H., Frieden, I. J., Drolet, B. A. 2022

  View details for DOI 10.1111/pde.15103

  View details for Web of Science ID 000851481700001

• Reply to: "Photodistributed toxic epidermal necrolysis in association with lamotrigine and tanning bed exposure". JAAD case reports Tjahjono, L., Young, K., Wanat, K., Siegel, D. 2022; 23: 164-165

  View details for DOI 10.1016/j.jdcr.2021.08.042

  View details for PubMedID 35519799

• Executive Summary: Consensus Recommendations for the Use of Retinoids in Ichthyosis and Other Disorders of Cornification in Children and Adolescents. Journal of the American Academy of Dermatology Zaenglein, A. L., Levy, M. L., Stefanko, N. S., Benjamin, L. T., Bruckner, A. L., Choate, K., Craiglow, B. G., DiGiovanna, J. J., Eichenfield, L. F., Elias, P., Fleckman, P., Lawley, L. P., Lewis, R. A., Lucky, A. W., Mathes, E. F., Milstone, L. M., Paller, A. S., Patel, S. S., Siegel, D. H., Teng, J., Tanumihardjo, S. A., Thaxton, L., Williams, M. L. 2021

  Abstract

  Topical and systemic retinoids are often used long-term in the treatment of ichthyoses and other disorders of cornification. The Pediatric Dermatology Research Alliance (PeDRA) Use of Retinoids in Ichthyosis Work Group was formed to address the numerous clinical concerns with use of these medications in children and adolescents and to establish best practices regarding the use of retinoids. Consensus was achieved using the Delphi process with recommendations based on the best available evidence and expert opinion. An executive summary of the results is presented herein.

  View details for DOI 10.1016/j.jaad.2021.08.047

  View details for PubMedID 34499997

• Consensus recommendations for the use of retinoids in ichthyosis and other disorders of cornification in children and adolescents. Pediatric dermatology Zaenglein, A. L., Levy, M. L., Stefanko, N. S., Benjamin, L. T., Bruckner, A. L., Choate, K., Craiglow, B. G., DiGiovanna, J. J., Eichenfield, L. F., Elias, P., Fleckman, P., Lawley, L. P., Lewis, R. A., Lucky, A. W., Mathes, E. F., Milstone, L. M., Paller, A. S., Patel, S. S., Siegel, D. H., Teng, J., Tanumihardjo, S. A., Thaxton, L., Williams, M. L., PeDRA Use of Retinoids in Ichthyosis Work Group 2020

  Abstract

  Topical and systemic retinoids have long been used in the treatment of ichthyoses and other disorders of cornification. Due to the need for long-term use of retinoids for these disorders, often beginning in childhood, numerous clinical concerns must be considered. Systemic retinoids have known side effects involving bone and eye. Additionally, potential psychiatric and cardiovascular effects need to be considered. Contraceptive concerns, as well as the additive cardiovascular and bone effects of systemic retinoid use with hormonal contraception must also be deliberated for patients of childbearing potential. The Pediatric Dermatology Research Alliance (PeDRA) Use of Retinoids in Ichthyosis Work Group was formed to address these issues and to establish best practices regarding the use of retinoids in ichthyoses based on available evidence and expert opinion.

  View details for DOI 10.1111/pde.14408

  View details for PubMedID 33169909

• Costello syndrome: Clinical phenotype, genotype, and management guidelines. American journal of medical genetics. Part A Gripp, K. W., Morse, L. A., Axelrad, M., Chatfield, K. C., Chidekel, A., Dobyns, W., Doyle, D., Kerr, B., Lin, A. E., Schwartz, D. D., Sibbles, B. J., Siegel, D., Shankar, S. P., Stevenson, D. A., Thacker, M. M., Weaver, K. N., White, S. M., Rauen, K. A. 2019

  Abstract

  Costello syndrome (CS) is a RASopathy caused by activating germline mutations in HRAS. Due to ubiquitous HRAS gene expression, CS affects multiple organ systems and individuals are predisposed to cancer. Individuals with CS may have distinctive craniofacial features, cardiac anomalies, growth and developmental delays, as well as dermatological, orthopedic, ocular, and neurological issues; however, considerable overlap with other RASopathies exists. Medical evaluation requires an understanding of the multifaceted phenotype. Subspecialists may have limited experience in caring for these individuals because of the rarity of CS. Furthermore, the phenotypic presentation may vary with the underlying genotype. These guidelines were developed by an interdisciplinary team of experts in order to encourage timely health care practices and provide medical management guidelines for the primary and specialty care provider, as well as for the families and affected individuals across their lifespan. These guidelines are based on expert opinion and do not represent evidence-based guidelines due to the lack of data for this rare condition.

  View details for DOI 10.1002/ajmg.a.61270

  View details for PubMedID 31222966

• The Fourth International Symposium on Genetic Disorders of the Ras/MAPK pathway AMERICAN JOURNAL OF MEDICAL GENETICS PART A Stevenson, D. A., Schill, L., Schoyer, L., Andresen, B. S., Bakker, A., Bayrak-Toydemir, P., Burkitt-Wright, E., Chatfield, K., Elefteriou, F., Elgersma, Y., Fisher, M. J., Franz, D., Gelb, B. D., Goriely, A., Gripp, K. W., Hardan, A. Y., Keppler-Noreuil, K. M., Kerr, B., Korf, B., Leoni, C., McCormick, F., Plotkin, S. R., Rauen, K. A., Reilly, K., Roberts, A., Sandler, A., Siegel, D., Walsh, K., Widemann, B. C. 2016; 170 (8): 1959-1966

  Abstract

  The RASopathies are a group of disorders due to variations of genes associated with the Ras/MAPK pathway. Some of the RASopathies include neurofibromatosis type 1 (NF1), Noonan syndrome, Noonan syndrome with multiple lentigines, cardiofaciocutaneous (CFC) syndrome, Costello syndrome, Legius syndrome, and capillary malformation-arteriovenous malformation (CM-AVM) syndrome. In combination, the RASopathies are a frequent group of genetic disorders. This report summarizes the proceedings of the 4th International Symposium on Genetic Disorders of the Ras/MAPK pathway and highlights gaps in the field. © 2016 Wiley Periodicals, Inc.

  View details for DOI 10.1002/ajmg.a.37723

  View details for PubMedID 27155140

• Proceedings of the Inaugural Pediatric Dermatology Research Alliance (PeDRA) Conference JOURNAL OF INVESTIGATIVE DERMATOLOGY Siegel, D. H., Choate, K. A., Drolet, B. A., Frieden, I. J., Rittenberg, S., Teng, J. M., Tom, W. L., Williams, M. L., Eichenfield, L. F., Paller, A. S. 2014; 134 (11): 2671-2674

  View details for DOI 10.1038/jid.2014.227

  View details for Web of Science ID 000343271200003

  View details for PubMedCentralID PMC4350365