Search Results (12)

Background: Neurofibromatosis type 1 (NF1) is a rare multisystem disorder characterized by variable expressivity and increased tumor risk. Café-au-lait macules (CALMs) are a hallmark of the disease, often representing one of the earliest clinical manifestations and allowing a clinical NF1 diagnosis if six or more are present. In this study, we aimed to investigate the prognostic value of CALMs at birth in NF1 patients. Methods: We conducted a retrospective study in patients aged ≥ 4 years presenting with CALMs at our Institution between 2020 and 2021, with a minimum follow-up of four years. We retrospectively collected data on CALMs at birth and other clinical manifestations associated with NF1. Results: Among 208 patients evaluated, including 147 with a confirmed diagnosis of NF1, 110 did not show CALMs at birth, and 98 had at least one. The absence of CALMs at birth did not correlate with a lower likelihood of NF1. In contrast, the CALM number at birth directly correlated with the likelihood of NF1, up to 95% in patients with ≥5 macules. Additionally, a higher number of CALMs correlated with a greater prevalence of plexiform neurofibromas (p < 0.001). Conclusions: Our findings suggest that a higher number of CALMs may indicate a more severe form of NF1, with an increased risk of plexiform neurofibromas. These results emphasize the importance of a comprehensive evaluation of patients with CALMs, especially in case of multiple lesions, aiming at implementing early NF1 diagnosis, follow-up strategies, and overall patient management. Full article

Sturge–Weber Syndrome (SWS) is a rare neurocutaneous disorder caused by a somatic nonsynonymous mosaic mutation most commonly in the GNAQ gene (G protein guanine Nucleotide-binding protein Alpha subunit q). SWS is characterized by capillary-venous malformations in the brain and eyes and a characteristic facial port wine (PW) birthmark (previously called port wine stain/PWS) in the head/neck region. Clinical manifestations vary and include epilepsy, stroke-like episodes, migraine headaches, cognitive delays, glaucoma, ocular vascular anomalies, heterochromia of the iris, visual field defects, and endocrine disorders like growth hormone deficiency or central hypothyroidism. The pathognomonic findings seen in neuroimaging with magnetic resonance imaging (MRI) include the presence of unilateral intracranial leptomeningeal angiomatosis, typically ipsilateral to the facial birthmark. SWS does not currently have a definitive cure, and management strategies focus on symptomatic management such as anti-seizure medications, limited surgical resection of the epileptogenic tissue or hemispherectomy for cases of drug-resistant epilepsy (DRE), selective photo-thermolysis of the PWS using a pulsed dye laser, and the medical and/or surgical management of glaucoma. In addition to these symptomatic treatments, the use of preventive, modifying, or stabilizing treatments like low-dose aspirin in reducing the frequency and severity of seizures and stroke-like events and the use of newer therapies like cannabidiols and mTOR inhibitors are being reviewed and have shown promising early results. This comprehensive narrative review summarizes the current literature on clinical management strategies, ongoing research studies, and future directions in the diagnosis and management of SWS. Full article

This essay explores the journey of co-authoring the children’s book Beauty With A Birthmark (2022) inspired by my experiences as a Black mother and those of my Black daughter, the main character in the book. Our book examines themes of beauty and self-acceptance, challenging traditional beauty standards and promoting the need for continually creating space for Black main characters in children’s books. Our essay further highlights the underrepresentation of Black protagonists in childhood picture books, acknowledging the pivotal role of gatekeepers in the publishing industry. We also address the impact of inclusive literature in classrooms and school libraries as it relates to Black children’s self-esteem, appreciation of and exposure to diversity, and academic achievement. Through this lens, Beauty With A Birthmark fosters belonging and confidence among young Black readers, illustrating the far-reaching influence that representation in children’s literature embodies. Full article

Sturge–Weber syndrome (SWS) is a rare congenital neurocutaneous disorder typically caused by a somatic mosaic mutation in R183Q GNAQ. At-risk children present at birth with a capillary malformation port-wine birthmark. The primary diagnostic characteristic of the disorder includes leptomeningeal enhancement of the brain, which demonstrates abnormal blood vessels and results in impaired venous drainage and impaired local cerebral perfusion. Impaired cerebral blood flow is complicated by seizures resulting in strokes, hemiparesis and visual field deficits, hormonal deficiencies, behavioral impairments, and intellectual disability. Therefore, anti-seizure medication in combination with low-dose aspirin is a common therapeutic treatment strategy. Recently published data indicate that the underlying mutation in endothelial cells results in the hyperactivation of downstream pathways and impairment of the blood–brain barrier. Cannabidiol (CBD) has been used to treat medically refractory seizures in SWS due to its anti-seizure, anti-inflammatory, and neuroprotective properties. Pilot research suggests that CBD improves cognitive impairment, emotional regulation, and quality of life in patients with SWS. Recent preclinical studies also suggest overlapping molecular pathways in SWS and in CBD, suggesting that CBD may be uniquely effective for SWS brain involvement. This review aims to summarize early data on CBD’s efficacy for preventing and treating epilepsy and neuro-cognitive impairments in patients with SWS, likely molecular pathways impacted, and provide insights for future translational research to improve clinical treatment for patients with SWS. Full article

Congenital dermal melanocytosis (DM) represents a common birthmark mainly found in children of Asian and darker skin phototype descent, clinically characterized by an oval blue-grey macule or macules, commonly located on the lumbosacral area. In rare DM cases, when presenting with diffuse macules persisting during the first years of life, it could represent a cutaneous feature of mucopolysaccharidoses (MPS). Extensive congenital DM is actually associated with Hurler syndrome (MPS type I) and Hunter syndrome (MPS type II), although several reports also described this association with MPS type VI and other lysosomal storage disorders (LySD), including GM1 gangliosidosis, mucolipidosis, Sandhoff disease, and Niemann–Pick disease. Here, we present the case of a two-year-old boy presenting with extensive dermal melanocytosis, generalized hypertrichosis, and chronic itch, harboring a heterozygous variant of uncertain significance, NM_152419.3: c.493C>T (p.Pro165Ser), in the exon 4 of HGSNAT gene, whose mutations are classically associated with MPS IIIC, also known as Sanfilippo syndrome. This is the first report that highlights the association between extensive congenital DM and MPS type IIIC, as well as a pathogenetic link between heterozygous LySD carrier status and congenital DM. We speculate that some cases of extensive congenital DM could be related to heterozygous LySD carriers, as a manifestation of a mild clinical phenotype. Full article

Port Wine Birthmarks (PWBs) are a congenital vascular malformation on the skin, occurring in 1–3 per 1000 live births. We have recently generated PWB-derived induced pluripotent stem cells (iPSCs) as clinically relevant disease models. The metabolites associated with the pathological phenotypes of PWB-derived iPSCs are unknown, and so we aim to explore them in this study. Metabolites were separated by ultra-performance liquid chromatography and screened with electrospray ionization mass spectrometry. Orthogonal partial least-squares discriminant, multivariate, and univariate analyses were used to identify differential metabolites (DMs). KEGG analysis was used to determine the enrichment of metabolic pathways. A total of 339 metabolites was identified. There were 22 DMs, among which nine were downregulated—including sphingosine—and 13 were upregulated, including glutathione in PWB iPSCs, as compared to controls. Pathway enrichment analysis confirmed the upregulation of glutathione and the downregulation of sphingolipid metabolism in PWB-derived iPSCs as compared to normal ones. We next examined the expression patterns of the key molecules associated with glutathione metabolism in PWB lesions. We found that hypoxia-inducible factor 1α (HIF1α), glutathione S-transferase Pi 1 (GSTP1), γ-glutamyl transferase 7 (GGT7), and glutamate cysteine ligase modulatory subunit (GCLM) were upregulated in PWB vasculatures as compared to blood vessels in normal skin. Other significantly affected metabolic pathways in PWB iPSCs included pentose and glucuronate interconversions; amino sugar and nucleotide sugars; alanine, aspartate, and glutamate; arginine, purine, D-glutamine, and D-glutamate; arachidonic acid, glyoxylate, and dicarboxylate; nitrogen, aminoacyl-tRNA biosynthesis, pyrimidine, galactose, ascorbate, and aldarate; and starch and sucrose. Our data demonstrated that there were perturbations in sphingolipid and cellular redox homeostasis in PWB vasculatures, which could facilitate cell survival and pathological progression. Our data implied that the upregulation of glutathione could contribute to laser-resistant phenotypes in some PWB vasculatures. Full article

Background: Port-wine stains (PWS) are congenital low-flow vascular malformations of the skin. PWS tend to become thicker and darker with time. Laser therapy is the gold standard and the first-line therapy for treating PWS. However, some resistant PWS, or PWS that have tissue hypertrophy, do not respond to this therapy. Our aim is to evaluate the role of surgery in the treatment of PWS birthmarks. Methods: A literature search was performed in PubMed, Scopus, Web of Science (WOS) and Google Scholar for all papers dealing with surgery for port-wine stains, from January 2010 to December 2020 using the search strings: (capillary vascular malformation OR port-wine stains OR Sturge Weber Syndrome OR sws OR pws) AND (surgical OR surgery). Results: Ten articles were identified and used for analysis. They were almost all case series with a short follow up period and lacked an objective–systematic score of evaluation. Conclusions: Delay in treatment of port wine stains may result in soft tissue and bone hypertrophy or nodules with disfiguring or destructive characteristics. The correction of PWS-related facial asymmetry often requires bone surgery followed by soft tissue corrections to achieve a more harmonious, predictable result. Full article

The effect of multiple general anesthesia (mGA) procedures administered in early life is a critical theme and has led the Food and Drug Administration (FDA) to issue an alert. This systematic review seeks to explore the potential effects on neurodevelopment of mGA on patients under 4 years. The Medline, Embase and Web of Science databases were searched for publications up to 31 March 2021. The databases were searched for publications regarding “children multiple general anesthesia OR pediatric multiple general anesthesia”. Case reports, animal studies and expert opinions were excluded. Systematic reviews were not included, but they were screened to identify any possible additional information. A total of 3156 studies were identified. After removing the duplicates, screening the remaining records and analyzing the systematic reviews’ bibliography, 10 studies were considered suitable for inclusion. Comprehensively, a total cohort of 264.759 unexposed children and 11.027 exposed children were assessed for neurodevelopmental outcomes. Only one paper did not find any statistically significant difference between exposed and unexposed children in terms of neurodevelopmental alterations. Controlled studies on mGA administered before 4 years of age support that there might be a greater risk of neurodevelopmental delay in children receiving mGA, warranting the need for careful risk/benefit considerations. Full article

Background: People socialize and receive education and training for the first time outside the home at school, where their teachers act as role models. Teachers play a crucial role in instilling sun-protection habits in children. Avoiding the sun between 10 a.m. and 4 p.m., staying in the shade, wearing sun-protective clothing, wearing sunglasses, wearing hats, using sunscreen products, and using an umbrella are some of the sun-protection methods described in the literature. This study sought to assess teachers’ skin cancer knowledge and attitudes (SC). Methods: In this cross-sectional study conducted between 21 September 2020, and 21 October 2020, 647 teachers from 30 schools in Kahramanmaras were included with their consent. The number of teachers employed at Kahramanmaras was 1863. Accordingly, the sample was found to be 641 with a 5% margin of error and a 99% confidence interval. Schools were selected by a simple random method. Teachers’ knowledge and behaviors were assessed using a 25-point questionnaire designed by the literature data to gauge the level of SC knowledge. Results: Of the 647 teachers included in this study, 230 (35.5%) were male, and 417 (64.5%) were female. The mean age of the participants was 38.44 ± 8.79 (min = 22, max = 65) years. The knowledge level of the teachers about SC was 13.54 ± 4.48 (min = 0, max = 23). The internet (75.9%) was the most preferred source of information. SC knowledge level was significantly higher in those with SC in their families and birthmarks on their bodies. (p < 0.001, p = 0.042, respectively). The rate of precaution taken to protect from the sun was higher in those with higher knowledge (p = 0.032). Women, primary school teachers, those with skin type 1, those with multiple nevi, and those with a high level of SC knowledge used statistically significantly more sunscreen (p = 0.001, p = 0.003, p < 0.001, p = 0.037, p = 0.002, respectively). Conclusions: It was found that the knowledge level of teachers about skin cancer and sun-protective behaviors was moderate. Correct behaviors increased as knowledge about SC grew. Information and recommendations made on the Internet should be made by experts. Additionally, health policymakers should implement projects aimed at improving teachers’ knowledge and behaviors and, through them, teaching students about SC; as such projects would significantly contribute to both public health and health economics. Full article

The behavioral immune system (BIS), which evolved to protect humans from infectious disease threats, prompts people to be sensitive to disease-connoting cues. A common denominator of many disease-connoting cues is benign physical abnormalities, such as birthmarks and obesity. Previous studies found that among people whose BIS was activated (e.g., people who were exposed to situational disease prime or chronically concerned about disease threat), disease-connoting cues could make people feel threatened by infectious disease and induce their malevolence. Malevolence is a necessary feature of malevolent creativity (MC), which is defined as creativity that deliberately leads to harmful or immoral results. According to the motivated focus account of creativity, a threat could promote creativity when creativity is relevant to the threat. Thus, infectious disease threats might increase malevolent creativity. However, whether infectious disease threats could influence MC is unknown. Therefore, the current study aims to explore the effect of infectious disease threat on MC by two disease-connoting cues (birthmark, obesity). In Study 1 (n = 174), a 2 (threat prime: infectious disease, natural disaster) × 2 (disease-connoting cue: birthmarked face, normal face) between-subjects design was used. Participants were asked to complete a malevolent creativity task (MCT). In Study 2 (n = 131), we used a perceived vulnerability to disease scale (PVD) to assess people’s dispositional tendencies of concerns about disease and selected high as well as low PVD participants. A 2 (PVD: high, low) × 2 (disease-connoting cue: obese, average-weight) between-subjects design was used. Participants were asked to complete the negotiation task to assess their MC. The results of Study 1 showed that, compared with participants in the normal face condition, participants in the birthmarked face condition showed higher MC fluency and total MC when they were exposed to situational disease prime. Compared with the natural disaster prime group, the infectious disease prime group showed higher MC fluency and total MC when they were provoked by a birthmark person. The results of Study 2 showed that, compared with the average-weight condition, the obese condition led to higher MC fluency and originality among high PVD participants. Compared with low PVD participants, high PVD participants showed higher MC fluency and originality when they negotiated with an obese person. Our studies suggest that among people whose BIS is situationally or chronically activated, birthmarks and obesity could increase MC, and people’s malevolent creativity might be induced by disease-connoting cues during the pandemic. Full article

Mucopolysaccharidoses (MPS) are a family of genetic diseases associated with a deficiency of alpha-L iduronidase, which causes a lack of catabolism of glycosaminoglycans (GAGs). Therefore, the accumulation of GAGs determines a wide spectrum of symptoms, typically found in a few syndromes like Hurler syndrome (HS). Among other specific manifestations, craniofacial abnormalities are crucial for the characterization of this syndrome. Ameloblastoma is a rare, benign, slow-growing, odontogenic tumor usually located in the mandible. Clear risk factors for the development of ameloblastoma remain unknown, but black patients have a fivefold increased risk. Clinically, it is characterized by a painless, variable-sized jaw swelling. Although classified as a benign tumor, ameloblastoma often has a severe clinical outcome. The most common type of ameloblastoma is the solid/multicystic/conventional one. A computed tomography scan (CT) with and without contrast is the gold standard for evaluating this kind of neoplasia. Conservative or radical surgery is the mainstay of treatment. In this case report, we described an unusual clinical assessment of conventional ameloblastoma interesting the posterior left mandible of a 35-month-old child affected by HS. This case represented a suggestive challenge both from a diagnostic and a therapeutic point of view. The patient was disease-free at 2 years’ follow-up. Full article

We suggest a novel method that uses artificial blood cells (hemoglobin vesicles, Hb-Vs) as photosensitizers in dye laser treatment (at 595-nm wavelength) for port-wine stains (i.e., capillary malformations presenting as red birthmarks) based on the results of animal experiments. As compared with human red blood cells, Hb-Vs have the same absorbance of 595 nm wavelength light and produce the same level of heat following dye laser irradiation. Small sized Hb-Vs (250 nm) distribute in the plasma phase in blood and tend to flow in the marginal zone of microvessels. Intravenous injections of Hb-Vs caused the dilatation of microvessels, and dye laser treatment with Hb-Vs destroyed the vessel wall effectively. Following the intravenous injection of Hb-Vs, the microvessels contained more Hb that absorbed laser photons and produced heat. This extra Hb tended to flow near the endothelial cells, which were the target of the laser treatment. These attributes of Hb-Vs will potentially contribute to enhancing the efficacy of dye laser treatment for port-wine stains. Hemoglobin is a type of porphyrin. Thus, our proposed treatment may have aspects of photodynamic therapy using porphyrin that leads to a cytotoxicity effect by active oxygen. Full article