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Somatic overgrowth disorders comprise a wide range of rare conditions that present with focal enlargement of one or more tissue types. The PI3K-AKT-mTOR pathway is a signalling pathway that induces angiogenesis and cell proliferation, and is one of the most commonly overactivated signalling pathways in cancer. The PI3K-AKT-mTOR pathway can be up-regulated by genetic variants that code for proteins in this pathway, or down-regulated by proteins that inhibit the pathway. Mosaic genetic variations can result in cells that proliferate excessively in specific anatomical locations. The PIK3CA-related overgrowth spectrum (PROS) disorders include CLOVES syndrome, macrodystrophia lipomatosa, and Klippel-Trenaunay syndrome among many. The neurofibromatosis type 1 (NF1) gene encodes neurofibromin which down-regulates the PI3K-AKT-mTOR pathway. Thousands of pathological variants in the NF1 gene have been described which can result in lower-than-normal levels of neurofibromin and therefore up-regulation of the PI3K-AKT-mTOR pathway promoting cellular overgrowth. Somatic overgrowth is a rare presentation in NF1 with a wide range of clinical and radiological presentations. Hypertrophy of all ectodermal and mesodermal elements has been described in NF1 including bone, muscle, fat, nerve, lymphatics, arteries and veins, and skin. The shared signalling pathway for cellular overgrowth means that these radiological appearances can overlap with other conditions in the PIK3CA-related overgrowth spectrum. The aim of this review is to describe the genetic basis for the radiological features of NF1 and in particular compare the appearances of the somatic overgrowth disorders in NF1 with other conditions in the PIK3CA-related overgrowth spectrum.

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Sotos syndrome is a rare overgrowth condition characterized by tall stature, distinctive facial features, and learning disabilities. It is primarily caused by a microdeletion of the nuclear receptor-binding set domain protein 1 (NSD1) gene on chromosome 5q35. Patients often present with various clinical manifestations, including tall stature, precocious puberty, cardiac anomalies, and mild intellectual disability. Management of Sotos syndrome involves a multidisciplinary approach due to its complex nature and potential comorbidities. This case discusses the management of a 10-year-old female with a known gene mutation consistent with Sotos syndrome that presented to the clinic with behavioral changes, and highlights the importance of integrated care models when addressing complex clinical scenarios.

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Objectives: Exhaled breath tests (BTs) are the main diagnostic method for fructose and lactose malabsorption/intolerance (FI and LI, respectively) and for detecting small intestine bacterial or methanogen overgrowth (SIBO/IMO). Although FI/LI-BTs may provide evidence of the presence of SIBO/IMO, there is limited literature evaluating their reliability for this purpose. The objective of this study was to assess the sensitivity and specificity of FI/LI-BTs in detecting SIBO and their concordance with SIBO-BTs in the identification of IMO. Methods: In this retrospective observational study, FI/LI-BTs and SIBO-BTs performed in the same patients within a period of 6 weeks were selected from 652 gas chromatography-based BTs. Results: A total of 146 BTs from 67 eligible adult patients were identified. LI-BTs had higher specificity than FI-BT in detecting SIBO (93.8 % vs. 72.7 %). In contrast, FI-BTs showed higher sensitivity (60.0 % vs. 28.6 %) as FI was more frequently established in SIBO-positive patients (70 % vs. 29 %). With regard to IMO, concordance with LI-BT was 100 %, with a 27 % of false negatives on FI-BTs. Conclusions: Findings suggestive of SIBO or IMO on LI-BTs were highly consistent with those of SIBO-BTs. In contrast, the rate of false positives for SIBO and the rate of false negative for IMO on FI-BTs was 27 % in both cases.

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Digestive functional disorders are among the most frequent reasons for medical consultation and a significant source of medical wandering. Therapeutic management of these patients is difficult, particularly due to the absence of specific treatment linked to an incomplete understanding of the pathophysiological mechanisms. In a certain number of these patients, the symptoms are accompanied by a small intestinal bacterial overgrowth (SIBO). This entity, historically identified in specific post-surgical situations, seems finally very common and associated with very diverse pathologies. The diagnosis of SIBO is currently being made more accessible through the development of breathing tests. Therapeutic management, based mainly on antibiotic therapy and diet, remains to date largely empirical because it is based on few studies but the growing interest in SIBO should make it possible to identify effective treatments during robust clinical trials.

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Background: Orthodontic therapy is a complex process involving a series of specialists in the dental field: the oral-maxillo-facial surgeon, the periodontologist, sometimes even the prosthetist, implantologist, or general practitioners. The injuries of the oral mucosa induced by orthodontic therapy include gingival overgrowths, traumatic lesions of the oral mucosa, different degrees of periodontal damage manifested by gingival retraction, alveolar bone resorption. Methods: From a total of 327 subjects who came to the Dental Clinic in Craiova 74 subjects were selected, who presented with gingival overgrowth associated with fixed orthodontic therapy. Subjects' age ranged from 14 to 56 years and experienced bleeding and gingival discomfort as well as alterations in physiognomic function. None of the patients included in the study have systemic diseases and are not under medical treatment. The clinical and statistical study took place between May 2022 and December 2023. Each patient was given a personal record containing personal data as well as oral and systemic health status. The examination of the periodontal status aimed at the evaluation of the following indices: assessment of oral hygiene using the OHI-S index and the O'Leary plaque index, assessment of superficial periodontal status using the Löe/Silness gingival inflammation index, periodontometry was performed in order to determine the depth of periodontal pockets, the level of gingival insertion, and the McGaw gingival overgrowth index. OHI-S index comprises two elements: the Debris Index and the Calculus Index. The purpose of our study is to present the incidence of cases of gingival overgrowth induced by fixed orthodontic therapy and to highlight how certain irritating factors can exacerbate the symptoms of gingival overgrowth of orthodontic etiology. Results: The majority of patients were female, aged between 30 and 55 years. Most clinically examined patients have presented with Grade II gingival hyperplasia. Factors that have exacerbated the symptoms of orthodontically induced gingival overgrowth include: incorrectly adapted prosthetic restorations, unpolished massive coronal fillings, root remnants, bacterial plaque, and tartar. Clinical examination of the oral cavity revealed the presence of gingival inflammation (localized or generalized), simple or complicated, treated and untreated odontal lesions, and coronal fillings made of light-curing composite material of significant size, being unfinished and unpolished, sometimes with sharp edges directly injuring the adjacent gingival mucosa, marginally incorrectly adapted prosthetic works. In the case of child and adolescent patients, significant amounts of bacterial plaque and tartar buildup were observed. In most of the cases examined, it was observed that the gingival overgrowth had a firm consistency, pinkish-reddish colour and gingival bleeding was evident during probing. Conclusion: Gingival overgrowth caused by orthodontics induces a number of important periodontal changes. It is worth noting that gingival overgrowth induced by fixed orthodontic therapy, in most of the cases examined, co-exists with favouring factors that amplify its severity. In our study, the favouring factors were bacterial plaque and calculus accumulation, sharp-edged odontal lesions, marginally ill-fitting prosthetic restorations or massive unfinished crown fillings. Therefore, removing the contributing factors can help improve the symptoms but also to reverse the inflammatory phenomena.

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Jansen metaphyseal chondrodysplasia (JMC) is an ultra-rare disorder caused by germline heterozygous PTHR1 variants resulting in constitutive activation of parathyroid hormone type 1 receptor. A description of ocular manifestations of the disease is lacking. Six patients with JMC underwent a detailed ophthalmic evaluation, spectral-domain optical coherence tomography (OCT), visual field testing, and craniofacial CT scans. Five of 6 patients had good visual acuity. All patients had widely spaced eyes; 5/6 had downslanted palpebral fissures. One patient had proptosis, and another had bilateral ptosis. Two patients had incomplete closure of the eyelids (lagophthalmos), one had a history of progressive right facial nerve palsy with profuse epiphora, while the second had advanced optic nerve atrophy with corresponding retinal nerve fiber layer (RNFL) thinning on OCT and significant bilateral optic canal narrowing on CT scan. Additionally, this patient also had central visual field defects and abnormal color vision. A third patient had normal visual acuity, subtle temporal pallor of the optic nerve head, normal average RNFL, but decreased temporal RNFL and retinal ganglion cell layer analysis (GCA) on OCT. GCA was decreased in 4/6 patients indicating a subclinical optic nerve atrophic process. None of the patients had glaucoma or high myopia. These data represent the first comprehensive report of ophthalmic findings in JMC. Patients with JMC have significant eye findings associated with optic canal narrowing due to extensive skull base dysplastic bone overgrowth that appear to be more prevalent and pronounced with age. Progressive optic neuropathy from optic canal narrowing may be a feature of JMC, and OCT GCA can serve as a useful biomarker for progression in the setting of optic canal narrowing. We suggest that patients with JMC should undergo regular ophthalmic examination including color vision, OCT, visual field testing, orbital, and craniofacial imaging.

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Overgrowth syndromes (OGS) comprise a heterogeneous group of disorders whose main characteristic is that the weight, height or the head circumference are above the 97th centile or 2-3 standard deviations above the mean for age, gender, and ethnic group. Several copy-number variants (CNVs) have been associated with the development of OGS, such as the 5q35 microdeletion or the duplication of the 15q26.1-qter, among many others. In this study, we have applied 850K SNP-arrays to 112 patients and relatives with OGS from the Spanish OverGrowth Registry Initiative. We have identified CNVs associated with the disorder in nine individuals (8%). Subsequently, whole genome sequencing (WGS) analysis was performed in these nine samples in order to better understand these genomic imbalances. All the CNVs were detected by both techniques, settling that WGS is a useful tool for CNV detection. We have found six patients with genomic abnormalities associated with previously well-established disorders and three patients with CNVs of unknown significance, which may be related to OGS, based on scientific literature. In this report, we describe these findings and comment on genes associated with OGS that are located within the CNV regions.

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This study aimed to identify risk factors for amlodipine-induced gingival enlargement, assess quality of life, and analyze gingival tissue. This cross-sectional study involved hypertensive patients on amlodipine, divided into groups with and without gingival enlargement. Assessments included sociodemographic data, clinical evaluations, and clinical parameters. Quality of life was assessed using OHIP-14 and WB-HRQoL scales. Gingival tissue samples were analyzed for oxidative status and key molecules using RT-PCR and colorimetric assays. The study included 32 patients with no significant sociodemographic differences between groups (p > 0.05). Patients with gingival enlargement had higher systolic blood pressure (139.63 ± 10.743 vs. 128.38 ± 7.249, p = 0.028) and higher OHIP-14 scores. The RT-PCR analysis showed significant differences in IL-6, TNF-α, IL-33, ST2, TGF-ß1, FGF-2, CTGF, VEGF-D, and KGF expression. IL-6, TNF-α, ST2, and FGF-2 expression levels were lower in patients taking amlodipine, with and without gingival enlargement. TGF-ß1 and CTGF expression levels were highest in patients with amlodipine-induced gingival enlargement. SOD activity was also highest in these patients, whereas MDA levels were higher in patients with gingival enlargement without amlodipine. Our study highlights the impact of amlodipine-induced gingival enlargement on oral health and quality of life, emphasizing fibrosis and oxidative stress, and suggests the need for integrated healthcare approaches and further research.

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Simpson-Golabi-Behmel syndrome (SGBS) is a rare congenital overgrowth condition characterized by macrosomia, macroglossia, coarse facial features, and development delays. It is caused by pathogenic variants in the GPC3 gene on chromosome Xq26.2. Here, we performed a comprehensive literature review and phenotyping of known patients with molecularly confirmed SGBS and reviewed a novel cohort of 22 patients. Using these data, we characterized the tumor risk for Wilms tumor and hepatoblastoma to suggest appropriate screening for this patient population. In addition, we discuss the phenotypic overlap between SGBS and Beckwith-Wiedemann Spectrum.

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This article aims to describe purposeful reimplantation and inflammatory fibrous hyperplasia cases caused due to poor dental health and malpositioning of teeth. A 17-year-old male patient was referred to a dental specialty hospital for soft tissue growth in the lower anterior tooth region. Anamnesis and clinical examination revealed that tooth #31 was severely hypoplastic. A surgical procedure and purposeful reimplantation were carried out, and a histological examination revealed inflammatory fibrous hyperplasia. During the follow-up appointments, it was feasible to see progress and the patient's satisfaction. Despite the low occurrence of inflammatory fibrous hyperplasia, it is important to note that tooth positioning outside of its normal alignment in the arch can contribute to plaque and calculus accumulation, which can then become etiological factors for inflammatory fibrous hyperplasia. As a result, dentists must be attentive in order to establish a diagnosis and therapeutic therapy as well as monitor these instances. How to cite this article: Gangwar A, Murry JN, Jungio MP, et al. Establishing Aesthetics by Purposeful Autoreimplantation in Inflammatory Fibrous Hyperplasia: A 12-Month Follow-up Case Report. Int J Clin Pediatr Dent 2024;17(2):216-220.

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Background: Gingival enlargement (GE) is a common clinical observation among orthodontic patients, yet its underlying causes remain unclear. This study aims to investigate the potential involvement of salivary matrix metalloproteinase (MMP)-2 and MMP-9 activity in orthodontic-induced GE. Materials and Methods: In this case-control study, we enrolled 50 subjects, including 25 individuals with GE and 25 without. The participants, aged 10-35 years, were in the 4th or 5th month of their orthodontic treatment. Comprehensive clinical assessments, encompassing plaque index, gingival index, and GE score were performed, and saliva samples were subjected to gelatin zymography to assess enzyme activity. Statistical analysis, including the Chi-square test for age distribution, independent samples t-test for age comparison between study groups, Mann-Whitney U test for MMP activity comparison, and Wilcoxon signed-rank test for comparison of data from the 4th to 5th months of treatment, was performed using SPSS version 23.0, with a significance level set at 0.05. Results: MMP-2 activity was undetectable in the zymograms. In the 4th month of treatment, MMP-9 activity was more prominent in the case group, though this disparity did not reach statistical significance in the 5th month. Furthermore, MMP-9 activity did not exhibit a correlation with the GE score. Conclusion: The activity of MMP-9 in the saliva of orthodontic patients with GE increases during the 4th month of treatment, but no correlation exists with the degree of GE.

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To investigate the impact of Small Intestinal Bacterial Overgrowth (SIBO) on the efficacy of Fecal Microbiota Transplantation (FMT) in patients with chronic constipation, our research team included 218 patients with chronic constipation treated with FMT. Based on the results of the SIBO breath test, the patients were divided into two groups: the constipation with SIBO group (SIBO) and the constipation without SIBO group (non-SIBO). The efficacy of the two groups was evaluated using constipation-related scoring scales. At the same time, feces and small intestinal fluid samples were collected from both groups before and after FMT to compare the changes in the intestinal microbiota through 16S rRNA sequencing. In this study, it was found that the clinical efficacy of FMT in the SIBO group was superior to that in the non-SIBO group. After FMT treatment, both groups showed a significant increase in bowel frequency and improvement in stool characteristics. Abdominal symptoms, rectal symptoms, and defecation symptoms were significantly alleviated (P < 0.05), and patients' quality of life was significantly enhanced (P < 0.05). After FMT, except for the Constipation Assessment Scale scores, other scale scores showed significant differences between the two groups, the SIBO group scoring significantly better than the non-SIBO group (P < 0.05). After FMT, there were minor changes in the colonic microbiota but more substantial changes in the small intestinal microbiota. At baseline, the SIBO group had a higher abundance of Veillonella, and lower abundances of Escherichia-Shigella and Acinetobacter compared to the non-SIBO group. Chronic constipation patients with SIBO have a better response to FMT than those without SIBO. IMPORTANCE: Existing studies have rarely considered the impact of the small intestine's microbial state on the efficacy of fecal microbiota transplantation (FMT), nor have they extensively explored the effect of the small intestine's microbial state on the recovery of colonic motility. Therefore, this study investigates the influence of small intestinal bacterial overgrowth (SIBO) on the efficacy of FMT in treating constipation, specifically the impact of the microbial state of the small intestine on the restoration of colonic homeostasis, and consequently on the recovery of colonic motility.

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In the contemporary era of medicine, exploring the complexity of the human body and its intricate interactions has become a central concern for health researchers. The main purpose of this article is to summarize the current understanding of relevant pathophysiological factors such as chronic inflammation, dysbiosis (microbial imbalance), and metabolic disorders, as well as etiological factors including dietary habits, lifestyle choices, obesity, metabolic syndrome, and genetic predispositions, as well as to emphasize potential avenues for upcoming studies and their medical significance. Additionally, this article aims to assess the potential impact of integrated treatment approaches on patient outcomes, emphasizing the need for interdisciplinary collaboration between gastroenterologists, dentists, and other healthcare professionals to develop comprehensive care plans that address both oral and digestive health issues simultaneously. Among the branches with a significant impact on general well-being are oral cavity health and digestive diseases, which have been the subject of intensive research in recent decades. In this context, analysis of the current state of knowledge on oral cavity disorders in relation to "modern" digestive diseases such as non-alcoholic fatty liver disease (NAFLD), small intestinal bacterial overgrowth (SIBO), inflammatory bowel disease (IBD), and irritable bowel syndrome (IBS) becomes essential for a deeper understanding of the interconnections between oral and digestive health. The temporal overlap or succession, whether preceding or following, of oral manifestations and digestive disorders should be taken seriously by both gastroenterologists and dentists to facilitate early diagnosis and explain to patients the correlation between these two body systems. In summary, this article underscores the importance of understanding the intricate relationship between oral and digestive health, advocating for interdisciplinary approaches to improve patient outcomes and guide future research.

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People with cystic fibrosis (pwCF) have an altered gastrointestinal microbiome. These individuals also demonstrate propensity toward developing small intestinal bacterial overgrowth (SIBO). The dysbiosis present has intestinal and extraintestinal implications, including potential links with the higher rates of gastrointestinal malignancies described in CF. Given these implications, there is growing interest in therapeutic options for microbiome modulation. Alternative therapies, including probiotics and prebiotics, and current CF transmembrane conductance regulator gene modulators are promising interventions for ameliorating gut microbiome dysfunction in pwCF. This article will characterize and discuss the current state of knowledge and expert opinions on gut dysbiosis and SIBO in the context of CF, before reviewing the current evidence supporting gut microbial modulating therapies in CF.

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Rifaximin is FDA-approved for treatment of irritable bowel syndrome with diarrhea (IBS-D), but poor solubility may limit its efficacy against microbes in the mucus layer, e.g. Escherichia coli. Here we evaluate adding the mucolytic N-acetylcysteine (NAC) to improve rifaximin efficacy. In a resazurin checkerboard assay, combining rifaximin with NAC had significant synergistic effects in reducing E. coli levels. The optimal rifaximin + NAC combination was then tested in a validated rat model of IBS-D (induced by cytolethal distending toxin [CdtB] inoculation). Rats were inoculated with vehicle and treated with placebo (Control-PBS) or rifaximin + NAC (Control-Rif + NAC, safety), or inoculated with CdtB and treated with placebo (CdtB-PBS), rifaximin (CdtB-Rifaximin), or rifaximin + NAC (CdtB-Rif + NAC) for 10 days. CdtB-inoculated rats (CdtB-PBS) developed wide variability in stool consistency (P = 0.0014) vs. controls (Control-PBS). Stool variability normalized in rats treated with rifaximin + NAC (CdtB-Rif + NAC) but not rifaximin alone (CdtB-Rifaximin). Small bowel bacterial levels were elevated in CdtB-PBS rats but normalized in CdtB-Rif + NAC but not CdtB-Rifaximin rats. E. coli and Desulfovibrio spp levels (each associated with different IBS-D microtypes) were also elevated in CdtB-inoculated (CdtB-PBS) but normalized in CdtB-Rif + NAC rats. Cytokine levels normalized only in CdtB-Rif + NAC rats, in a manner predicted to be associated with reduced diarrhea driven by reduced E. coli. These findings suggest that combining rifaximin with NAC may improve the percentage of IBS-D patients responding to treatment.

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OBJECTIVE: This study evaluated anthropometric, biochemical, and inflammatory biomarkers, as well as dietary intake in Brazilian children diagnosed with small intestinal bacterial overgrowth (SIBO) and compared them with their counterparts without SIBO. METHODS: This was a cross-sectional study with 106 children aged 7 to 10 years. A glucose-hydrogen breath test was performed to diagnose small intestinal bacterial overgrowth (SIBO). Anthropometric and dietary characteristics were assessed. Blood samples were collected and serum biochemical parameters and cytokines were measured. RESULTS: The occurrence of SIBO was 13.2%. Age, BMI, BMI/age WC, BFP, sex and biochemical markers were similar between SIBO-positive and SIBO-negative children (p > 0.05). High consumption of ultra-processed foods tended to be higher in SIBO-positive compared to SIBO-negative children (47.8 ± 8.2 vs. 42.6 ± 9.5, p = 0.06). Serum levels of IL-17 were higher in SIBO-positive than in SIBO-negative children [69.5 (5.4-125.7) vs. 53.4 (2.3-157.7), p = 0.03], while serum levels of IL-10 were lower in SIBO-positive than in SIBO-negative children [2.3 (0.6-7.2) vs. 5.7 (0.5-30.8), p = 0.04]. Finally, in a logistic regression adjusted for sex, BMI and age, consumption of ultra-processed foods (p = 0.03) and IL-6 levels (p = 0.003) were found to contribute to the occurrence of SIBO. CONCLUSION: this study identified for the first time an occurrence of 13% of SIBO in children living in the northeastern region of Brazil and showed that consumption of ultra-processed foods and serum levels of IL-6 may influence the occurrence of the SIBO in the pediatrics population.

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BACKGROUND & AIMS: Archaea constitute one of the main 3 domains of the tree of life, distinct from eukaryotes and bacteria. Excessive luminal loads of methanogenic archaea (intestinal methanogen overgrowth [IMO]) have been implicated in the pathophysiology of various diseases, including constipation. To elucidate the phenotypical presentation of IMO, we performed a systematic review and meta-analysis of the prevalence and severity of gastrointestinal symptoms in subjects with IMO as compared with subjects without IMO. METHODS: Electronic databases, including OVID MEDLINE and Cochrane Database from inception until September 2023, were systematically searched. Prevalence rates, odds ratios (ORs), standardized mean difference (SMD), and 95% confidence intervals (CIs) of symptoms were calculated. RESULTS: Nineteen studies were included (1293 patients with IMO and 3208 controls). Patients with IMO exhibited various gastrointestinal symptoms, including bloating (78%), constipation (51%), diarrhea (33%), abdominal pain (65%), nausea (30%), and flatulence (56%). Patients with IMO had a significantly higher prevalence of constipation as compared with controls (47% vs 38%; OR, 2.04; 95% CI, 1.48-2.83; P < .0001) along with lower prevalence of diarrhea (37% vs 52%; OR, 0.58; 95% CI, 0.37-0.90; P = .01) and nausea (32% vs 45%; OR, 0.75; 95% CI, 0.60-0.94; P = .01). Patients with IMO had higher severity of constipation (SMD, 0.77; 95% CI, 0.11-1.43; P = .02) and lower severity of diarrhea (SMD, -0.71; 95% CI, -1.39 to -0.03; P = .04). Significant heterogeneity was detected. CONCLUSION: Patients with IMO exhibit a higher rate and severity of constipation along with lower rate and severity of diarrhea. The distinct phenotype of patients with IMO should be incorporated in patient-reported outcome measures and further correlated with mechanistic microbiome studies.

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OBJECTIVES: As reported by the existing literature, calcium-channel blockers (CCB) can lead to gingival enlargement. The aims of this study were to investigate the factors associated with gingival enlargement in patients on CCB and to assess the saliva and gingival crevicular fluid (GCF) profile of patients on CCB with gingival enlargement. METHODS: A total of 131 participants were included. Data were collected from 91 patients taking CCB for treatment of systemic hypertension. The presence of drug-induced gingival enlargement (DIGE) was assessed clinically and associated with patient factors. Patients with DIGE were group-matched for gender and ethnicity with an equal number of consecutive CCB non-DIGE patients (control 1), no-CCB no-DIGE (control 2) and periodontally healthy with no DIGE (control 3) for the saliva and GCF analysis. A bead-based multiplex immunoassay was used to assess a panel of biomarkers. RESULTS: Twenty-two percent of patients on CCB were diagnosed with DIGE. Lack of daily interdental cleaning and self-reported diagnosis of type II diabetes were associated with the diagnosis of DIGE. When analysing patients only on CCB, those with DIGE had higher GCF levels of vascular endolthelial growth factor (VEGF) (p = 0.032), epidermal growth factor (EGF) (p = 0.030) and matrix metalloproteinase-8 (MMP-8) (p = 0.008). Among the salivary markers, only MMP-8 showed a statistically significant difference across groups (p < 0.001). CONCLUSIONS: This is the first study investigating saliva and GCF biomarkers in patients with DIGE and different control groups, suggesting that causes of the overgrowth might involve inflammatory processes, tissue damage pathways, and potentially an impact on growth factors like VEGF. Future research should verify these results in independent populations and explore the underlying pathogenic mechanisms in-depth. CLINICAL SIGNIFICANCE: Calcium-channel blockers (CCB) can lead to gingival enlargement. This study confirms lack of interdental cleaning and type II diabetes as risk factors. Elevated levels of VEGF, EGF, and MMP-8 in gingival crevicular fluid and MMP-8 in saliva suggest inflammatory processes and growth factors might play roles in this condition.

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BACKGROUND: Malan syndrome (MALNS), previously referred to as "Sotos syndrome 2" due to its resemblance to Sotos syndrome (SS), is an ultra-rare neurodevelopmental disorder characterized by overgrowth, typical craniofacial features, intellectual disability (ID), and a range of psychobehavioral, musculoskeletal, vision and neurological signs. As MALNS and SS partly overlap, it is essential to more accurately profile their clinical presentations and highlight their differences in order to improve syndrome specific management. An increasing number of individuals with MALNS reach adult-age though the natural history of the disorder is poorly characterized due to the small number of adult individuals described so far. As a consequence, current guidelines are limited to the pediatric population. Further delineation of MALNS is essential to optimize care in adulthood. RESULTS: A mixed approach based on cross-sectional data collection with a survey disseminated to caregivers of adults with molecularly confirmed MALNS and literature review was conducted. Twenty-eight caregivers completed the survey. Clinical presentation in adulthood is multisystemic and defined by psychobehavioral comorbidities (96%), musculoskeletal involvement (96%), vision impairment (96%) and neurological complications (86%). The most common signs were anxiety (79%), hypotonia (75%), movement difficulty (75%), scoliosis (64%), problems with coordination (61%), strabismus (57%), constipation (54%), breastbone abnormalities (54%) and advanced bone age during childhood (54%). Impaired vision was complicated by vision decline (36%) and optic atrophy (32%). We report some previously unidentified features, including high pain threshold (46%), incontinence (25%), tremors (21%), muscle hypoplasia (18%) and tics (18%). CONCLUSIONS: This survey in the adult population has allowed a more complete description of the natural history of MALNS. Our findings will contribute to the development and improvement of standards of care for adults with MALNS to assure optimal health monitoring and treatment of evolutive complications. We propose additional recommendations to the previous dataset of clinical evaluations specifically applied to adults. The comparison of MALNS and SS adult presentation highlights significant differences in terms of prevalence and severity of ID, behavioral issues, and vision problems, confirming that a proper differential diagnosis between the two conditions is indispensable to guide physicians and mental health professionals to syndrome specific management.

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SOLAMEN syndrome is a rare, recently recognized congenital syndrome that is characterized by progressive and hypertrophic diseases involving multiple systems, including segmental overgrowth, lipomatosis, arteriovenous malformation (AVM) and epidermal nevus. According to literatures, SOLAMEN syndrome is caused by heterozygous PTEN mutation. Phenotypic overlap complicates the clinical identification of diseases associated with PTEN heterozygous mutations, making the diagnosis of SOLAMEN more challenging. In addition, SOLAMEN often presents with segmental tissue overgrowth and vascular malformations, increasing the possibility of misdiagnosis as klipple-trenaunay syndrome or Parks-Weber syndrome. Here, we present a case of a child presenting with macrocephaly, patchy lymphatic malformation on the right chest, marked subcutaneous varicosities and capillaries involving the whole body, overgrowth of the left lower limb, a liner epidermal nevus on the middle of the right lower limb, and a large AVM on the right cranial thoracic entrance. Based on the typical phenotypes, the child was diagnosed as SOLAMEN syndrome. detailed clinical, imaging and genetic diagnoses of SOLAMEN syndrome was rendered. Next-generation sequencing (NGS) data revealed that except for a germline PTEN mutation, a PDGFRB variant was also identified. A subsequent echocardiographic examination detected potential cardiac defects. We suggested that given the progressive nature of AVM and the potential severity of cardiac damage, regular echocardiographic evaluation, imaging follow-up and appropriate interventional therapy for AVM are recommended.

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