No COVID-19 pandemic impact on incidence and clinical presentation of celiac disease in Italian children.

AIM: We aimed to evaluate the impact of Coronavirus Disease-19 (COVID-19) pandemic on the incidence and clinical presentation of celiac disease (CD) in children. METHODS: The diagnoses of CD were compared between the COVID-19 pandemic (from April 2020 to March 2022) and the pre-pandemic period (from April 2018 to March 2020) in three Italian Paediatric Gastroenterology centres (Varese, Como, Catanzaro). Electronic patient records were reviewed and additional information were collected through parental interview. The diagnosis of CD was made according to ESPGHAN criteria. SARS-CoV-2 infection was diagnosed based on pre-vaccination positive serum antibodies or nasopharyngeal swabs. Z test and chi-square were used for statistical analysis. RESULTS: The overall number of paediatric diagnosis of CD did not differ between the two years pre-pandemic and pandemic periods (177 and 172 cases) in the three Italian participating centres. Clinical presentation of CD was also similar throughout the study periods. SARS-CoV-2 infection has been documented in 10.6% of children but only in 5.8% of these occurred before CD diagnosis. CONCLUSION: Different to what reported for other autoimmune diseases, the incidence and presenting symptoms of CD in our paediatric population did not change during the COVID-19 pandemic compared to the previous 2 years.

Italian guidelines for the management of irritable bowel syndrome in children and adolescents : Joint Consensus from the Italian Societies of: Gastroenterology, Hepatology and Pediatric Nutrition (SIGENP), Pediatrics (SIP), Gastroenterology and Endoscopy (SIGE) and Neurogastroenterology and Motility (SINGEM).

The irritable bowel syndrome (IBS) is a functional gastrointestinal disorder (FGID), whose prevalence has widely increased in pediatric population during the past two decades. The exact pathophysiological mechanism underlying IBS is still uncertain, thus resulting in challenging diagnosis and management. Experts from 4 Italian Societies participated in a Delphi consensus, searching medical literature and voting process on 22 statements on both diagnosis and management of IBS in children. Recommendations and levels of evidence were evaluated according to the grading of recommendations, assessment, development, and evaluation (GRADE) criteria. Consensus was reached for all statements. These guidelines suggest a positive diagnostic strategy within a symptom-based approach, comprehensive of psychological comorbidities assessment, alarm signs and symptoms' exclusion, testing for celiac disease and, under specific circumstances, fecal calprotectin and C-reactive protein. Consensus also suggests to rule out constipation in case of therapeutic failure. Conversely, routine stool testing for enteric pathogens, testing for food allergy/intolerance or small intestinal bacterial overgrowth are not recommended. Colonoscopy is recommended only in patients with alarm features. Regarding treatment, the consensus strongly suggests a dietary approach, psychologically directed therapies and, in specific conditions, gut-brain neuromodulators, under specialist supervision. Conditional recommendation was provided for both probiotics and specific fibers supplementation. Polyethylene glycol achieved consensus recommendation for specific subtypes of IBS. Secretagogues and 5-HT4 agonists are not recommended in children with IBS-C. Certain complementary alternative therapies, antispasmodics and, in specific IBS subtypes, loperamide and rifaximin could be considered.

To Diet or Not to Diet This Is the Question in Food-Protein-Induced Allergic Proctocolitis (FPIAP)-A Comprehensive Review of Current Recommendations.

Food-protein-induced allergic proctocolitis (FPIAP) is an increasingly reported transient and benign form of colitis that occurs commonly in the first weeks of life in healthy breastfed or formula-fed infants. Distal colon mucosal inflammation is caused by a non-IgE immune reaction to food allergens, more commonly to cow's milk protein. Rectal bleeding possibly associated with mucus and loose stools is the clinical hallmark of FPIAP. To date, no specific biomarker is available, and investigations are reserved for severe cases. Disappearance of blood in the stool may occur within days or weeks from starting the maternal or infant elimination diet, and tolerance to the food allergen is typically acquired before one year of life in most patients. In some infants, no relapse of bleeding occurs when the presumed offending food is reassumed after a few weeks of the elimination diet. Many guidelines and expert consensus on cow's milk allergy have recently been published. However, the role of diet is still debated, and recommendations on the appropriateness and duration of allergen elimination in FPIAP are heterogeneous. This review summarizes and compares the different proposed nutritional management of infants suffering from FPIAP, highlighting the pros and cons according to the most recent literature data.

Nutraceuticals and Pain Disorders of the Gut-Brain Interaction in Infants and Children: A Narrative Review and Practical Insights.

Different nutraceuticals are often considered by parents of infants and children with abdominal pain and disorders of the gut-brain interaction. Herb extracts and natural compounds have long been used in traditional medicine, but clinical pediatric trials are very limited. This narrative review based on relevant studies identified through a search of the literature in Pubmed and Medline updated to October 2023 focused on the effect of nutraceuticals in infantile colic, functional abdominal pain, and irritable bowel syndrome in children and adolescents. Significant reductions in colic episodes and crying time were reported in two studies on fennel (seeds oil or tea), in three studies on different multiple herbal extracts (all including fennel), in one study on Mentha piperita, and in at least two double-blind randomized controlled studies on Lactobacillus reuteri DSM 17938 and Bifidobacterium lactis BB-12 (108 CFU/day for at least 21 days) in breast-fed infants. Compared to a placebo, in children with functional abdominal pain or irritable bowel syndrome, a significant reduction in pain was reported in two studies supplementing peppermint oil capsules or psyllium fibers, and in one study on corn fiber cookies, partial hydrolyzed guar gum, a specific multiple herbal extract (STW-5), or vitamin D supplementation. To date, there is moderate-certainty evidence with a weak grade of recommendation on Lactobacillus reuteri DSM 17938 (108 CFU/day) in reducing pain intensity in children with functional abdominal pain and for Lactobacillus rhamnosus GG (1-3 × 109 CFU twice daily) in reducing pain frequency and intensity in children with IBS. Further large and well-designed pediatric studies are needed to prove the efficacy and safety of different herbal extracts and prolonged use of studied products in infants and children with pain disorders of the gut-brain interaction.

Diagnostic and therapeutic approach to children with chronic refractory constipation: Consensus report by the SIGENP motility working group.

Constipation is a common problem in children, accounting for about 3% of all primary care visits and up to 25% of referrals to paediatric gastroenterologists. Although polyethylene glycol often proves effective, most children require prolonged treatment and about 50% of them have at least one relapse within the first 5 years after initial recovery. When conventional treatment fails, children are considered to have refractory constipation. Children with refractory constipation deserve specialist management and guidance. Over the last decades, there has been a remarkable increase in our knowledge of normal and abnormal colonic and anorectal motility in children, and a number of different techniques to measure transit and motility have been developed. The present review analyses the possible diagnostic investigations for children with refractory constipation, focusing on their actual indications and their utility in clinical practice. Moreover, we have also analytically reviewed medical and surgical therapeutic options, which should be considered in selected patients in order to achieve the best clinical outcome.

Dietary Fibers in Healthy Children and in Pediatric Gastrointestinal Disorders: A Practical Guide.

Dietary fibers include non-digestible plant carbohydrates, lignin and resistant starch. Dietary fibers provide immune, cardiovascular, metabolic and intestinal beneficial effects in humans. Fibers naturally present in foods (fruits, vegetables, legumes, cereals) or used as supplements have different physical, chemical and functional profiles. This narrative review provides an update to the knowledge on the effects of dietary fibers in healthy subjects and in children with gastrointestinal disorders. Soluble fibers are digested by gut bacteria, producing short-chain fatty acids and energy for colonocytes, and may exert prebiotic effects that promote the growth of bifidobacteria and lactobacilli. Non-soluble fibers are bulking agents and may improve intestinal transit. The exact amount and characteristics of the fiber requirement in infants and children need to be further established. There are limited data evaluating fibers in children with gastrointestinal disorders. The low intake of fibers has been associated with constipation, but the intake of excessive fibers is not recommended as it may cause flatulence and abdominal discomfort. Certain fibers (particularly psyllium in irritable bowel syndrome) have shown beneficial effects in children with gastrointestinal disorders, but the limited and heterogenous data do not currently allow a specific recommendation.

Prevalence of functional gastrointestinal disorders in Italian children living in different regions: analysis of the difference and the role of diet.

BACKGROUND: Functional Gastrointestinal Disorders (FGIDs) are common in pediatric age. AIMS: To estimate the prevalence of FGIDs in Italian children and evaluate the impact of diet. METHODS: Healthy children aged 4-18 years were recruited in a multicenter cross-sectional study. We evaluated their eating habits and the presence of FGIDs, using Rome IV criteria, 3-day food diaries and Mediterranean Diet Quality Index (KIDMED) questionnaires. RESULTS: Seven hundred forty subjects were enrolled:369 children aged 4-9 years (Group A), and 371 adolescents 10-18 years old (Group B). The overall prevalence of FGIDs was 26.4% in Group A and 26.2% in Group B, with a significant higher prevalence in females in both groups. The most frequent disorders were functional constipation, functional dyspepsia, and abdominal migraine. No significant difference in FGIDs prevalence was found between Northern and Southern Italy, despite significant variation in diet. In Group A there was a significant difference in KIDMED between North and South (5.3 ± 1 vs 6 ± 1.2, respectively; p = 0.001). A significant association between FGIDs and KIDMED was found in Group A (OR=0.83, p = 0.034), but not in Group B (OR=0.89, p = 0.166). CONCLUSIONS: FGIDs are common in Italian children, with a higher prevalence in females. Despite significant differences in dietary habits between North and South, FGIDs prevalence does not vary significantly.

Prevalence of Non-erosive Esophageal Phenotypes in Children: A European Multicenter Study.

Background/Aims: Since available data on pediatric non-erosive esophageal phenotypes (NEEPs) are scant, we investigated their prevalence and the phenotype-dependent treatment response in these children. Methods: Over a 5-year period, children with negative upper endoscopy, who underwent esophageal pH-impedance (off-therapy) for persisting symptoms not responsive to proton pump inhibitor (PPI)-treatment, were recruited. Based on the results of acid reflux index (RI) and symptom association probability (SAP), patients were categorized into: (1) abnormal RI (non-erosive reflux disease [NERD]), (2) normal RI and abnormal SAP (reflux hypersensitivity [RH]), (3) normal RI and normal SAP (functional heartburn [FH]), and (4) normal RI and not-reliable SAP (normal-RI-not otherwise-specified [normal-RI-NOS]). For each subgroup, treatment response was evaluated. Results: Out of 2333 children who underwent esophageal pH-impedance, 68 cases, including 18 NERD, 14 RH, 26 FH, and 10 normal-RI-NOS were identified as fulfilling the inclusion criteria and were analyzed. Considering symptoms before endoscopy, chest pain was more reported in NERD than in other cases (6/18 vs 5/50, P = 0.031). At long-term follow-up of 23 patients (8 NERD, 8 FH, 2 RH, and 5 normal-RI-NOS): 17 were on PPIs and 2 combined alginate, 1 (FH) was on benzodiazepine + anticholinergic, 1 (normal-RI-NOS) on citalopram, and 3 had no therapy. A complete symptom-resolution was observed in 5/8 NERD, in 2/8 FH, and in 2/5 normal-RI-NOS. Conclusions: FH may be the most common pediatric NEEP. At long-term follow-up, there was a trend toward a more frequent complete symptom resolution with PPI-therapy in NERD patients while other groups did not benefit from extended acid-suppressive-treatment.

Safety and Efficacy of Split-Dose Thiopurine vs Low-Dose Thiopurine-Allopurinol Cotherapy in Pediatric Inflammatory Bowel Disease.

INTRODUCTION: Split-dose thiopurine and allopurinol-thiopurine cotherapy strategies have been suggested as rescue therapeutic options for children with inflammatory bowel disease (IBD) and impaired thiopurine metabolism. We compared the efficacy and safety of these regimens in patients who previously failed conventional thiopurine treatment. METHODS: Children with IBD treated with split-dose thiopurine or low-dose thiopurine-allopurinol cotherapy were retrospectively identified. Medical records were reviewed for demographics, treatment regimen, reason for thiopurine failure, side effects, and discontinuation of treatment. Laboratory findings were evaluated at different time points. RESULTS: After prior therapeutic failure, 42 patients were on split-dose regimen (group A) and 20 patients were on thiopurine-allopurinol cotherapy (group B). Twelve patients crossed from group A to group B because of treatment failure, 1 patient was lost at follow-up, and 1 patient discontinued the treatment. The final cotherapy group comprised 29 children (group C), while the split-dose group (group D) included 31 children. Intention-to-treat analysis showed significant differences between split-dose regimen and thiopurine-allopurinol cotherapy for 6-thioguanine nucleotide (6-TGN)/6-methyl mercaptopurine (6-MeMP) ratio ( P < 0.001), 6-TGN ( P < 0.05), and 6-MeMP ( P < 0.001) at 1-3 months. As per protocol analysis, there was a significant difference between group C and group D at 6 months for 6-MeMP ( P < 0.05) and 6-TGN/6-MeMP ratio ( P < 0.05) and at 12 months for 6-MeMP ( P < 0.05) and 6-TGN/6-MeMP ratio ( P < 0.001). Side effects were more frequent in allopurinol-thiopurine cotherapy ( P < 0.05). DISCUSSION: In children with IBD and impaired thiopurine metabolism, split-dose thiopurine and low-dose thiopurine-allopurinol cotherapy are both effective therapeutic strategies. The latter shows higher efficacy but a higher side effect rate, suggesting the use of split-dose regimen as the first-line approach.

Role of inflammation in pediatric irritable bowel syndrome.

BACKGROUND: IBS affects a large number of children throughout the world and is thought to be the result of disturbed neuroimmune function along with the brain-gut axis. Although the underlying pathophysiologic mechanisms are not clear, the role of low-grade inflammation and mucosal immune activation in IBS symptom generation has become evident also in subsets of pediatric patients. Animal models provided meaningful insight in the causal relationship between abnormal mucosal immune activation and changes in gastrointestinal (GI) sensory-motor function. Likewise, the development of long-standing GI symptoms fulfilling the current criteria for functional GI disorders after infection gastroenteritis and in patients with IBD or celiac disease in remission further supports this hypothesis. Immune activation, its impact on gut sensory-motor function, and potential implications for symptom generation emerged in both children and adults with IBS. PURPOSE: The aim of this review is to summarize the main evidence on the presence of low-grade inflammation and immune activation in children with IBS, its possible role in symptom generation, and its potential implication for new therapeutic strategies.

Cyclic vomiting syndrome in children: a nationwide survey of current practice on behalf of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) and Italian Society of Pediatric Neurology (SINP).

BACKGROUND: Cyclic Vomiting Syndrome (CVS) is a rare functional gastrointestinal disorder, which has a considerable burden on quality of life of both children and their family. Aim of the study was to evaluate the diagnostic modalities and therapeutic approach to CVS among Italian tertiary care centers and the differences according to subspecialties, as well as to explore whether potential predictive factors associated with either a poor outcome or a response to a specific treatment. METHODS: Cross-sectional multicenter web-based survey involving members of the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition (SIGENP) and Italian Society of Pediatric Neurology (SINP). RESULTS: A total of 67 responses were received and analyzed. Most of the respondent units cared for less than 20 patients. More than half of the patients were referred after 3 to 5 episodes, and a quarter after 5 attacks. We report different diagnostic approaches among Italian clinicians, which was particularly evident when comparing gastroenterologists and neurologists. Moreover, our survey demonstrated a predilection of certain drugs during emetic phase according to specific clinic, which reflects the cultural background of physicians. CONCLUSION: In conclusion, our survey highlights poor consensus amongst clinicians in our country in the diagnosis and the management of children with CVS, raising the need for a national consensus guideline in order to standardize the practice.

A Novel Bispecific T-Cell Engager (CD1a x CD3ε) BTCE Is Effective against Cortical-Derived T Cell Acute Lymphoblastic Leukemia (T-ALL) Cells.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy burdened by poor prognosis. While huge progress of immunotherapy has recently improved the outcome of B-cell malignancies, the lack of tumor-restricted T-cell antigens still hampers its progress in T-ALL. Therefore, innovative immunotherapeutic agents are eagerly awaited. To this end, we generated a novel asymmetric (2 + 1) bispecific T-cell engager (BTCE) targeting CD1a and CD3ε (CD1a x CD3ε) starting from the development of a novel mAb named UMG2. UMG2 mAb reacts against CD1a, a glycoprotein highly expressed by cortical T-ALL cells. Importantly, no UMG2 binding was found on normal T-cells. CD1a x CD3ε induced high T-cell mediated cytotoxicity against CD1a+ T-ALL cells in vitro, as demonstrated by the concentration-dependent increase of T-cell proliferation, degranulation, induction of cell surface activation markers, and secretion of pro-inflammatory cytokines. Most importantly, in a PBMC-reconstituted NGS mouse model bearing human T-ALL, CD1a x CD3ε significantly inhibited the growth of human T-ALL xenografts, translating into a significant survival advantage of treated animals. In conclusion, CD1a x CD3ε is a novel BTCE highly active against CD1a-expressing cortical-derived T-ALL cells suitable for clinical development as an effective therapeutic option for this rare and aggressive disease.

miR-221/222 as biomarkers and targets for therapeutic intervention on cancer and other diseases: A systematic review.

Among deregulated microRNAs (miRs) in human malignancies, miR-221 has been widely investigated for its oncogenic role and as a promising biomarker. Moreover, recent evidence suggests miR-221 as a fine-tuner of chronic liver injury and inflammation-related events. Available information also supports the potential of miR-221 silencing as promising therapeutic intervention. In this systematic review, we selected papers from the principal databases (PubMed, MedLine, Medscape, ASCO, ESMO) between January 2012 and December 2020, using the keywords "miR-221" and the specific keywords related to the most important hematologic and solid malignancies, and some non-malignant diseases, to define and characterize deregulated miR-221 as a valuable therapeutic target in the modern vision of molecular medicine. We found a major role of miR-221 in this view.

Cows' Milk Allergy-Associated Constipation: When to Look for It? A Narrative Review.

Constipation is a very common disorder, mostly functional in nature, that may persist for years in up to 35-52% of children. Food allergy prevalence, severity and persistence are increasing over time, and cows' milk protein is the commonest food allergen recognised to affect gastrointestinal motility in children. There is mounting evidence of the role of cows' milk (CM) allergy (CMA) in children with constipation. With this narrative review, we aim to provide clinicians with an updated and critical overview of food allergy-associated constipation. We searched Embase, Medline and the Cochrane Library, using keywords related to the topic. Only reviews and studies including children aged 0-17 years that were published in English were considered. Constipation has been reported in 4.6% of infants with CMA; the prevalence of food allergy underlying chronic constipation in children resistant to conventional treatment and presenting to tertiary clinics ranges between 28% and 78%. The identification of predisposing risk factors and of a specific phenotype of food allergy-induced constipation remains elusive. No allergic tests, radiological or motility investigations achieve sufficient sensitivity and specificity to screen children for CMA-related constipation. A 4-week cows' milk protein (CMP) elimination diet may be considered for children with chronic constipation resistant to conventional treatment and who lack alarm sign/symptoms of organic diseases. In subjects with ameliorated symptoms on CMP elimination, the diagnosis of CMA should be confirmed by a food challenge to avoid an unnecessary protracted diet.

Functional Gastrointestinal Disorders in Mediterranean Countries According to Rome IV Criteria.

OBJECTIVES: The aim of this study was to assess the prevalence of functional gastrointestinal disorders (FGIDs) in children of Mediterranean area using Rome IV criteria and to compare the prevalence of FGIDs using Rome IV and Rome III criteria. METHODS: This was a cross-sectional study enrolling children and adolescents living in Croatia, Greece, Israel, Italy, Macedonia, and Serbia. Subjects were examined in relation to the presence of FGIDs, using the Rome IV criteria. Data were compared with the results of a previous study using Rome III data. RESULTS: We analyzed 1972 children ages 4 to 9 years (group A), and 2450 adolescents 10 to 18 years old (group B). The overall prevalence of FGIDs was 16% in group A and 26% in group B, with statistical differences among countries in both groups (P < 0.001). In group A, the prevalence of FGIDs and of functional constipation (FC) was significantly lower than in the previous study (P < 0.001), whereas in group B no significant difference was found. In both groups of age, the prevalence of abdominal migraine and irritable bowel syndrome decreased significantly (P < 0.001 and P < 0.001, respectively) using Rome IV versus Rome III criteria, conversely functional dyspepsia increased (P < 0.001). CONCLUSIONS: FGIDs are common in children and adolescents, their frequency increases with age, and there is a significant variation in the prevalence of some FGIDs among different European countries. The application of the Rome IV criteria resulted in a significantly lower prevalence of FGIDs in children compared with Rome III criteria.

Autoimmune colitis and neutropenia in adjuvant anti-PD-1 therapy for malignant melanoma: efficacy of Vedolizumab, a case report.

Immune checkpoint inhibitors (ICIs) represent an important advance in the adjuvant treatment of patients with high-risk melanoma. Although the safety profile of anti-programmed cell death protein-1 (PD-1) is fairly acceptable, different immune-related adverse events (irAEs) are described. Herein we report for the first time a notably multidisciplinary combined approach on a malignant melanoma (MM) patient treated with anti-PD-1 antibody in adjuvant setting. In this novel approach, corticosteroid-refractory immune-mediated colitis (IMC) was effectively treated with Vedolizumab, a selective blockade of the α4ß7 integrin and corticosteroids were successfully administered for autoimmune neutropenia. Notably, our patient also express HLA-B*35, a potential biomarker for predicting a genetic basis of autoimmune susceptibility. Our experience offers a possible future perspective about the use of Vedolizumab together with immunotherapy in a strategic early approach for high-risk patients genotyped for HLA.

Tools in Pharmacogenomics Biomarker Identification for Cancer Patients.

The understanding of the biological differences which underlie the inter-individual variability in drug response improved the efficacy of cancer therapy in the era of precision medicine. In fact molecularly targeted drugs and immunotherapy represent a revolution in cancer treatment. The identification of genetic predictive and/or prognostic biomarkers linked to drug pharmacokinetics (PK) and pharmacodynamics (PD) is allowed by the development of high-throughput omics tools for detecting and understanding biological differences among individuals, in order to improve drug efficacy and minimize risk of toxicity. Personalized medicine in cancer treatment reduces costs of the healthcare system. Unfortunately, pharmacogenomics biomarkers discovery is influenced by complexity, need of high-quality evidence, and a validation process for regulatory purposes. This chapter is focused on the critic analysis of presently available pharmacogenomics tools for discovering or testing genetic polymorphic variants in drug metabolizing enzyme to be introduced in clinical practice for the prospective stratification of cancer patients.

Integration of DNA Microarray with Clinical and Genomic Data.

DNA microarrays have been widely employed to understand cancer development. This technology is able to measure expression levels of a large numbers of genes or to genotype multiple regions of a genome in a massively parallel experiment. In addition, the detection of methylation patterns and gene copy number variations are also performed. Clinicians began to apply these findings in personalized medicine for the selection of cancer therapy according to the individual's cancer genomic profile. Because cancer is a complex disease it is of great value to integrate microarray data with genomic and clinical data. Here, we presented an overview of DNA microarray technology and discuss about benefits and challenging of microarray data integration.

Ferric carboxymaltose treatment for iron deficiency anemia in children with inflammatory bowel disease: Efficacy and risk of hypophosphatemia.

BACKGROUND: Although intravenous ferric carboxymaltose (FCM) is effective in treating iron deficiency anemia (IDA) in paediatric inflammatory bowel disease (pIBD), no data are available on its post-infusion related risks. AIMS: We assessed the efficacy of FCM and the rate of post-infusion hypophosphatemia in a large cohort of children with IBD and IDA. METHODS: All children with IBD with IDA treated with FCM over 5-year period were reviewed. Disease activity, biohumoral assessment and treatments were evaluated at baseline, 4-6 and 12 weeks after each infusion. RESULTS: 128 patients [median age at first infusion: 13 years] were identified, 81 (63.3%) were <14 years, 10 (7.8%) <6 years. Eighty-three children (64.8%) received one infusion, whilst 45 (35.2%) repeated infusions. A significant increase in Hb (p<0.001), iron (p<0.001) and ferritin (p<0.001) was observed 4-6 and 12 weeks post-infusion. Hb gain was unrelated to disease severity. Low baseline iron was the main predicting factor for repeated infusions (p<0.05). Three patients reported infusion reactions, none <6 years. Twenty-five children had low post-infusion serum phosphate (11 were <14 years, 3 <6 years). Two children developed severe hypophosphatemia. CONCLUSIONS: FCM administration is effective for IDA management in pIBD, including children <6 years. Due to the high prevalence of post-infusion hypophosphatemia, serum phosphate monitoring should be mandatory.

Facial Dysmorphisms, Macrodontia, Focal Epilepsy, and Thinning of the Corpus Callosum: A Rare Mild Form of Kabuki Syndrome.

Kabuki syndrome (KS) is a rare genetic condition with multiple congenital abnormalities and developmental delay. The cardinal manifestations of KS include characteristic facial features, intellectual disability, skeletal defects, dermatoglyphic abnormalities, and postnatal growth deficiencies. Cardiac and urological malformations are commonly present in patient with KS, as well as language deficits and immunological abnormalities. Here, we reported a case of a child with an atypical form of KS, associated with macrodontia, corpus callosum dysmorphism, focal epilepsy responsive to antiepileptic treatment, and a novel KMT2D gene missense variant, c.2413C > T, never reported to date.