Multidisciplinary follow-up in a patient with Morgagni hernia leads to diagnosis of Marfan syndrome.

BACKGROUND: congenital diaphragmatic hernia (CDH) is a birth defect occurring in isolated or syndromic (chromosomal or monogenic) conditions. The diaphragmatic defect can be the most common one: left-sided posterolateral, named Bochdalek hernia; or it can be an anterior-retrosternal defect, named Morgagni hernia. Marfan syndrome (MFS) is a rare autosomal dominant inherited condition that affects connective tissue, caused by mutations in fibrillin-1 gene on chromosome 15. To date various types of diaphragmatic defects (about 30 types) have been reported in association with MFS, but they are heterogeneous, including CDH and paraesophageal hernia. CASE PRESENTATION: We describe the case of a child incidentally diagnosed with Morgagni hernia through a chest X-ray performed due to recurrent respiratory tract infections. Since the diagnosis of CDH, the patient underwent a clinical multidisciplinary follow-up leading to the diagnosis of MFS in accordance with revised Ghent Criteria: the child had typical clinical features and a novel heterozygous de novo single-base deletion in exon 26 of the FBN1 gene, identified by Whole-Exome Sequencing. MFS diagnosis permitted to look for cardiovascular complications and treat them, though asymptomatic, in order to prevent major cardiovascular life-threatening events. CONCLUSION: Our case shows the importance of a long-term and multidisciplinary follow-up in all children with diagnosis of CDH.

Matrisome and Immune Pathways Contribute to Extreme Vascular Outcomes in Williams-Beuren Syndrome.

BACKGROUND: Supravalvar aortic stenosis (SVAS) is a characteristic feature of Williams-Beuren syndrome (WBS). Its severity varies: ~20% of people with Williams-Beuren syndrome have SVAS requiring surgical intervention, whereas ~35% have no appreciable SVAS. The remaining individuals have SVAS of intermediate severity. Little is known about genetic modifiers that contribute to this variability. METHODS AND RESULTS: We performed genome sequencing on 473 individuals with Williams-Beuren syndrome and developed strategies for modifier discovery in this rare disease population. Approaches include extreme phenotyping and nonsynonymous variant prioritization, followed by gene set enrichment and pathway-level association tests. We next used GTEx v8 and proteomic data sets to verify expression of candidate modifiers in relevant tissues. Finally, we evaluated overlap between the genes/pathways identified here and those ascertained through larger aortic disease/trait genome-wide association studies. We show that SVAS severity in Williams-Beuren syndrome is associated with increased frequency of common and rarer variants in matrisome and immune pathways. Two implicated matrisome genes (ACAN and LTBP4) were uniquely expressed in the aorta. Many genes in the identified pathways were previously reported in genome-wide association studies for aneurysm, bicuspid aortic valve, or aortic size. CONCLUSIONS: Smaller sample sizes in rare disease studies necessitate new approaches to detect modifiers. Our strategies identified variation in matrisome and immune pathways that are associated with SVAS severity. These findings suggest that, like other aortopathies, SVAS may be influenced by the balance of synthesis and degradation of matrisome proteins. Leveraging multiomic data and results from larger aorta-focused genome-wide association studies may accelerate modifier discovery for rare aortopathies like SVAS.

Laparoscopic Treatment of Gastroesophageal Reflux Disease. Outcomes and Quality of Life. A Long Term Follow-Up Study.

Background: This study evaluates the feasibility, efficacy, the complications rate, and the long-term results of laparoscopic treatment of gastroesophageal reflux disease (GERD) at a dedicated center. Materials and Methods: From 01/11/1993 to 01/12/2019, we performed 620 fundoplication surgeries by laparoscopic approach according to Rossetti technique and 160 according to Toupet technique, totally 780 procedures for gastroesophageal reflux disease. The average duration of surgery was 40 minutes (range 19 - 160) for Rossetti fundoplication, 50 (range 30 - 180), and for Toupet 60 (range 45 - 190). All patients were investigated by upper digestive tract radiography, esophagogastroscopy, 24h computerized pH-metry, manometry and scintigraphy to assess esophageal clearance and gastric emptying times. In the 180 (23 %) patients with associated hiatal hernia, direct hiatoplasty was performed in 108 cases, and hiatoalloplasty in the remaining 72. Results: There were no cases of perioperative mortality; the morbidity rate was 6.28 %. We had 16.7 % long-term failures, requiring reintervention in 46 cases (6.5 %). Thirty patients (3.84 %) had to resume occasional 40 mg PPI therapy and 48 patients (6.15 %) had to resume 40 mg PPI therapy continuously. Manometry in these patients revealed lower esophageal sphincter tone between 10- and 16-mm hg with complete and coordinated relaxations. Of the 44 patients who underwent redo surgery 26 were reoperated to repackage a tighter plastic. Six patients required reoperation for dysphagia. Twelve paraesophageal hernias were recorded in the group of patients in whom only hiatoplasty without prosthesis was performed. In all cases, a hiatoplasty with prosthesis was repackaged laparoscopically. Conclusions: We emphasize the importance of accurate morphologic and functional evaluation of the esophagus preoperatively for selection of the most appropriate intervention and postoperatively for evaluation of the causes of failures. In the presence of hiatal hernia, it is always advisable to perform hiatoplasty with the placement of a prosthesis.

Laparoscopic Sleeve Gastrectomy in Patients Over 60 Years Old: A Long-Term Follow-Up.

Purpose: This study analyzed the safety and effectiveness of laparoscopic sleeve gastrectomy (LSG) in patients over 60 years old, in a long-term follow-up, in a high-volume bariatric center. Methods: We retrospectively analyzed all patients older than 60 years who underwent LSG in our center from January 2009 to December 2018. A prospectively collected database of 4991 consecutive LSG cases was reviewed. Results: One hundred seventy-nine sleeve gastrectomy procedures were performed in patients older than 60 years, 135 were aged 60-65 years (group A) and 44 were older than 65 years (group B). We reported five cases (2.7%) of early complications: three postoperative hemorrhages, one cardial leakage, and one perigastric abscess. No thromboembolic events or mortality rates were reported. The mean follow-up period was 5.5 years (66 months). The follow-up loss rate was about 29%. At last follow-up, the mean body-mass index/body mass/percentage of excess weight loss values were, respectively, 33.7 ± 7/86.1 ± 21/60.4 ± 28.6 in group A and 32.4 ± 6.4/82.6 ± 18/61.8 ± 33 in group B. We reported 5 (4.0%) trocar site hernias, 1 (0.8%) cardial junction stenosis, and 22 (18%) new outbreaks of gastroesophageal reflux (GERD). There were 7 reinterventions (5.7%): 5 for weight regain and 2 for GERD not responding to medical therapy. There were no statistically significant differences between the two age groups. Conclusions: LSG is a safe and effective treatment for severe obesity in people over 60 years old. There are no differences in results of patients over 65 years and between 60 and 65 years old. Scales that include associated medical problems and the patient's general condition must be considered.

Role of Preoperative High-Resolution Manometry in the Identification of Patients at High Risk of Postoperative GERD Symptoms 1 Year After Sleeve Gastrectomy.

PURPOSE: Sleeve gastrectomy (SG) has become the most common bariatric procedure, but it is often characterized by the onset of postoperative gastroesophageal reflux disease (GERD). High-resolution manometry (HRM) is a useful tool to detect risk factors for GERD. The aim of this study was to evaluate preoperative manometric parameters as possible predictors of postoperative GERD. MATERIALS AND METHODS: This was a monocentric retrospective study. We analyzed 164 patients, with preoperative esophagitis/GERD symptoms who underwent preoperative HRM and were submitted to SG (July 2020-February 2022). RESULTS: Postoperative GERD was observed in 60 patients (36.6%): 41 of them (68%) already had preoperative GERD symptoms, whereas the remaining 19 patients (32%) developed postoperative symptoms. Female patients developed postoperative GERD in a significantly higher fraction of cases as compared to male patients (82% versus 18%; p < 0.001). DCI (distal contractile integral) was identified as the only HRM parameter correlating with the presence of GERD. Patients with DCI ≤ 1623 mmHg*cm*s developed postoperative GERD in 46% of cases (n = 43/94), as compared to 24% of cases (n = 17/70) among patients with DCI > 1623 mmHg*cm*s (p = 0.005). At multivariable analysis, female sex (OR 3.402, p = 0.002), preoperative GERD symptoms (OR 2.489, p = 0.013), and DCI ≤ 1623 mmHg*s*cm (OR 0.335, p = 0.003) were identified as independent determinants of postoperative GERD. CONCLUSION: All the patients with preoperative risk factors for reflux, such as GERD symptoms or esophagitis on EGDS (esophagogastroduodenoscopy), should be considered for an HRM. Moreover, when a DCI ≤ 1623 mmHg*s*cm is found, a bariatric procedure different from SG might be considered.

Chung-Jansen syndrome can mimic Cornelia de Lange syndrome: Another player among chromatinopathies?

Cornelia de Lange syndrome (CdLS) is a rare multisystem congenital neurodevelopmental disorder (NDD) characterized by distinctive facial anomalies, short stature, developmental delay, hirsutism, gastrointestinal abnormalities and upper limb reduction defects. CdLS syndrome is associated with causative variants in genes encoding for the cohesin complex, a cellular machinery involved in chromatid pairing, DNA repair and gene-expression regulation. In this report, we describe a familial case of a syndromic presentation in a 4-year-old patient (P1) and in his mother (P2). Trio-based Whole Exome Sequencing (WES) performed on P1 was first negative. Since his phenotypic evolution during the follow-up was reminiscent of the CdLS spectrum, a reanalysis of WES data, focused on CdLS-related genes, was requested. Although no alterations in those genes was detected, we identified the likely pathogenetic variant c.40G > A (p.Glu14Lys) in the PHIP gene, in the meanwhile associated with Chung-Jansen syndrome. Reverse phenotyping carried out in both patients confirmed the molecular diagnosis. CHUJANS belongs to NDDs, featuring developmental delay, mild-to-moderate intellectual disability, behavioral problems, obesity and facial dysmorphisms. Moreover, as here described, CHUJANS shows a significant overlap with the CdLS spectrum, with specific regard to facial gestalt. On the basis of our findings, we suggest to include PHIP among genes routinely analyzed in patients belonging to the CdLS spectrum.

Re-sleeve gastrectomy: weight loss, comorbidities and gerd evaluation in a large series with 5 years of follow-up.

INTRODUCTION: Laparoscopic sleeve gastrectomy (SG) has rapidly become one of the most commonly performed procedures in bariatric surgery. Weight regain and insufficient weight loss are the most common causes for surgical failure. Re-sleeve gastrectomy (ReSG) can represent an option when there is evidence of a dilated gastric tube. OBJECTIVES: The aim of the study is to evaluate safety, efficacy and rate of gastro-esophageal reflux disease (GERD) after ReSG in one of the largest series present in literature with long-term follow up. METHODS AND STUDY DESIGN: Retrospective study design. From February 2010 to August 2018, 102 patients underwent ReSG at our Centre. We divided patients into two groups, according to the main reason for surgical failure: insufficient weight loss or progressive weight regain. RESULTS: One hundred-two patients (78 women, 24 men) with BMI 38 ± 6 kg/m2 underwent ReSG (mean age 44 years). Rate of postoperative complications was 3.9% (4/102). After a mean follow-up of 55 months, mean BMI decreased to 30,4 kg/m2 and the mean percentage of excess weight loss (%EWL) was 51 ± 38.6. Symptoms of GERD were present in 35/102 patients (34.3%) and the need for a new operation occurred in six patients. Forty-five patients were submitted to ReSG for progressive weight regain (group A) and 57 for insufficient weight loss (group B). No differences were found in terms of postoperative BMI and %EWL. CONCLUSION: ReSG is a feasible procedure after primary SG failure in selected patients, but its efficacy in reducing the BMI under 30 kg/m2 is still unclear. In addition, over 30% of patients suffer from long-term gastro-esophageal reflux.

Congenital diaphragmatic hernia in Coffin Siris syndrome: Further evidence from two cases.

Coffin-Siris Syndrome (CSS) is a rare multi-system dominant condition with a variable clinical presentation mainly characterized by hypoplasia/aplasia of the nail and/or distal phalanx of the fifth digit, coarse facies, hirsutism/hypertrichosis, developmental delay and intellectual disability of variable degree and growth impairment. Congenital anomalies may include cardiac, genitourinary and central nervous system malformations whereas congenital diaphragmatic hernia (CDH) is rarely reported. The genes usually involved in CSS pathogenesis are ARID1B (most frequently), SMARCA4, SMARCB1, ARID1A, SMARCE1, DPF2, and PHF6. Here, we present two cases of CSS presenting with CDH, for whom Whole Exome Sequencing (WES) identified two distinct de novo heterozygous causative variants, one in ARID1B (case 1) and one in SMARCA4 (case 2). Due to the rarity of CDH in CSS, in both cases the occurrence of CDH did not represent a predictive sign of CSS but, on the other hand, prompted genetic testing before (case 1) or independently (case 2) from the clinical hypothesis of CSS. We provide further evidence of the association between CSS and CDH, reviewed previous cases from literature and discuss possible functional links to related conditions.

Short stature in PRMT7 Mutations: first evidence of response to growth hormone treatment.

Protein arginine methyltransferase 7 (PRMT7) pathogenetic variants have been associated with the human disorder of Short Stature, Brachydactyly, Intellectual Developmental Disability and Seizures syndrome (SBIDDS). Only 15 cases have been described in the literature. Here we report two female dizygotic twins with novel compound heterozygous deleterious variants of PRMT7 and describe the associated endocrine manifestations and short-term response to recombinant growth hormone (rGH) treatment. They were born at 36 + 3 weeks from a dichorionic diamniotic twin pregnancy. Twin A was appropriate for gestational age while Twin B was small for gestational age. Whole exome sequencing analyses showed the same novel compound heterozygous genetic defects in the PRMT7 gene (c.1220 G > A of maternal origin; c.1323 + 2 T > G of paternal origin, Fig. 1). Due to severe short stature and growth impairment, at six years of age, endocrine investigations were performed to rule out growth hormone (GH) deficiency, and revealed GH deficiency (GHD) in Twin A and an appropriate GH response in Twin B. Therefore, both started rGH, albeit at different dosages according to the underlying diagnosis. Both showed a satisfactory short-term response to treatment with height gain (∆HT) of +0.52 SDS (Twin A) and +0.88 SDS (Twin B) during the first year. In conclusion, our findings expand the knowledge about the endocrine manifestations associated with PRMT7 pathogenetic variants, including GH deficiency and rGH response. Further studies are needed to investigate long-term outcomes and establish whether PRMT7 genetic defects can be included among syndromic short stature treatable with rGH.

Pitfalls of whole exome sequencing in undefined clinical conditions with a suspected genetic etiology.

BACKGROUND: Whole-Exome Sequencing (WES) is a valuable tool for the molecular diagnosis of patients with a suspected genetic condition. In complex and heterogeneous diseases, the interpretation of WES variants is more challenging given the absence of diagnostic handles and other reported cases with overlapping clinical presentations. OBJECTIVE: To describe candidate variants emerging from trio-WES and possibly associated with the clinical phenotype in clinically heterogeneous conditions. METHODS: We performed WES in ten patients from eight families, selected because of the lack of a clear clinical diagnosis or suspicion, the presence of multiple clinical signs, and the negative results of traditional genetic tests. RESULTS: Although we identified ten candidate variants, reaching the diagnosis of these cases is challenging, given the complexity and the rarity of these syndromes and because affected genes are already associated with known genetic diseases only partially recapitulating patients' phenotypes. However, the identification of these variants could shed light into the definition of new genotype-phenotype correlations. Here, we describe the clinical and molecular data of these cases with the aim of favoring the match with other similar cases and, hopefully, confirm our diagnostic hypotheses. CONCLUSION: This study emphasizes the major limitations associated with WES data interpretation, but also highlights its clinical utility in unraveling novel genotype-phenotype correlations in complex and heterogeneous undefined clinical conditions with a suspected genetic etiology.

Celiac disease prevalence and predisposing-HLA in a cohort of 93 Williams-Beuren syndrome patients.

Williams-Beuren syndrome is considered to be at increased risk for celiac disease, as for recent literature data and celiac disease guidelines, despite pathogenic mechanisms are still unclear. Our study analyzed the prevalence of autoimmune disorders, HLA DQ2 and/or DQ8 haplotypes, of transglutaminase antibodies and of diagnosis of celiac disease in a cohort of 93 Williams-Beuren syndrome's patients (mean age 21.26 years). Our study showed an increased prevalence of celiac disease equal to 10.8% (10/93 patients). We did not find a significant different frequency of predisposing HLA in subjects with Williams-Beuren syndrome compared to literature data in the general population (49.5% vs. 42.9%, with p > .1), nor a susceptibility to autoimmunity. This suggests that the increased prevalence of celiac disease in Williams-Beuren syndrome cannot be ascribed to HLA haplotype and may be related to other factors that still need to be identified in these patients.

Promoting engagement with quality communication in social media.

The COVID-19 pandemic made explicit the issues of communicating science in an information ecosystem dominated by social media platforms. One of the fundamental communication challenges of our time is to provide the public with reliable content and contrast misinformation. This paper investigates how social media can become an effective channel to promote engagement and (re)build trust. To measure the social response to quality communication, we conducted an experimental study to test a set of science communication recommendations on Facebook and Twitter. The experiment involved communication practitioners and social media managers from select countries in Europe, applying and testing such recommendations for five months. Here we analyse their feedback in terms of adoption and show that some differences emerge across platforms, topics, and recommendation categories. To evaluate these recommendations' effect on users, we measure their response to quality content, finding that the median engagement is generally higher, especially on Twitter. The results indicate that quality communication strategies may elicit positive feedback on social media. A data-driven and co-designed approach in developing counter-strategies is thus promising in tackling misinformation.

Prenatal overgrowth and polydramnios: Would you think about Noonan syndrome?

We report on a child with prenatal findings of increased nuchal translucency, polydramnios, ascites, and overgrowth. At birth, she presented length >97° centile, minor facial anomalies, megalencephaly, and Wolff-Parkinson-White syndrome. Whole-exome sequencing showed a pathogenic variant in the NRAS gene, but no mutations were found in PI3K/AKT/mTOR pathway genes.

CHARGE syndrome presenting with persistent hypoglycemia: case report and overview of the main genetic syndromes associated with neonatal hypoglycemia.

BACKGROUND: CHARGE syndrome (CS) is an autosomal dominant genetic condition whose recognition in the neonatal period is complicated by considerable phenotypic variability. Pediatric patients with genetic disorders have a known high incidence of hypoglycemia, due to many concurring factors. To date, neonatal hypoglycemia is a feature poorly explored in the literature associated with CS. This paper adds to the existing literature on hypoglycemia in CS and provides a brief review of the mechanisms through which CS, as well as the main genetic syndromes associated with neonatal hypoglycemia, may determine it. CASE PRESENTATION: The patient was a term newborn, first-born daughter to non-consanguineous parents. At birth, axial hypotonia with slight hypertonia of the limbs, and dysplastic auricles were noted. The incidental finding of asymptomatic hypoglycemia led to the initiation of glucose infusion on the II day of life, continued for a total of 8 days (maximum infusion rate: 8 mg/kg/min). In-depth endocrinological examinations showed poor cortisol response to the hypoglycemic stimulus, with normal GH values, thyroid function and ACTH. In view of the suspected hypoadrenalism, oral hydrocortisone therapy was initiated. Inappropriately low values of plasmatic and urinary ketones supported the hypothesis of concomitant transient hyperinsulinism, not requiring therapy. A brain MRI was performed, documenting thinning of the optic nerves, non-displayable olfactory bulbs and dysmorphic corpus callosum. An eye examination revealed bilateral chorioretinal coloboma. Temporal bone CT scan showed absence of the semicircular canals. The unexpected findings of coloboma and absence of semicircular canals led to the suspicion of CS, later confirmed by the molecular analysis of CHD7. CONCLUSIONS: It seems important to consider CS in the differential diagnosis of persistent hypoglycemia in newborns with specific anomalies. At the same time, it is advisable to consider the risk of hypoglycemia in children with CS, as well as other genetic syndromes. Awareness of the many possible causes of hypoglycemia in newborns with genetic conditions may help steer the investigations, allowing for an appropriate and timely treatment.

Laparoscopic sleeve gastrectomy with Rossetti fundoplication: long-term (5-year) follow-up.

BACKGROUND: Gastroesophageal reflux disease (GERD), including erosive esophagitis, is highly prevalent in the obese population. Barrett's esophagus is the consequence of untreated GERD. Laparoscopic sleeve gastrectomy is one of the most frequently performed bariatric procedures. This study presents results after 5 years of follow-up of combined LSG and Rossetti fundoplication for the treatment of GERD, esophagitis, and Barrett's esophagus in patients with morbid obesity. OBJECTIVE: To evaluate long-term results after sleeve gastrectomy with Rossetti fundoplication. SETTING: Public university hospital in Italy. METHODS: Since January 2015, more than 450 patients with obesity underwent sleeve gastrectomy with a Rossetti fundoplication procedure as part of prospective studies underway at our center performed by 4 different expert bariatric surgeons. Currently, 127 patients have a follow-up of 5 years or more. RESULTS: Mean patient age was 42.9 ± 10.3 years, and mean body mass index was 42.4 ± 6.1 kg/m2. In total, 74.8% of patients were experiencing GERD before surgery. In 29 of 127 patients (22.8%), preoperative gastroscopy showed signs of esophagitis and/or Barrett's esophagus. In particular, 23 of 127 patients (18.1%) had grade A esophagitis, 2 of 127 (1.6%) had grade B, 2 of 127 (1.6%) had grade C, and 2 of 127 (1.6%) had Barrett's esophagus. Mean operative time was 51 ± 21 minutes. No intraoperative complications or conversions were reported. A regular postoperative course was seen in 91.3% of patients. Sixty months after surgery, more than 95% of patients did not experience any reflux symptoms. Percent total weight loss at follow-up was comparable with that with sleeve gastrectomy. Endoscopic follow-up demonstrated improvement of esophagitis lesions (including Barrett's esophagus) present in the preoperative setting. CONCLUSION: Laparoscopic sleeve gastrectomy with Rossetti fundoplication is well tolerated, feasible, and safe in patients with obesity, providing adequate weight loss results and complete resolution of clinical signs of GERD. We have recorded an improvement in esophagitis lesions present at preoperative gastroscopy and complete resolution of Barrett's esophagus within 5 years of follow-up.

Family history is key to the interpretation of exome sequencing in the prenatal context: unexpected diagnosis of Basal Cell Nevus Syndrome.

OBJECTIVES: To reach a molecular diagnosis for a family with two consecutive fetuses presenting with multiple congenital anomalies. METHODS: The two fetuses underwent prenatal ultrasound, autopsy, radiologic, and genetic investigation. Genetic analysis included karyotype and array-CGH for both fetuses and trio-based whole exome sequencing (WES) only for the second fetus. RESULTS: WES results, initially focusing on recessive or dominant de novo variants, were negative.However, as a result of new relevant information regarding family history, the variant c.648_651dup in the PTCH1 gene was identified as causative of the fetal phenotype. CONCLUSIONS: This case further highlights how WES data analysis and interpretation strongly rely on family history and robust genotype-phenotype correlation. This is even more relevant in the prenatal setting, where access to fetal phenotype is limited and prenatal recognition of many morbid genes is not fully explored. We also provide a detailed description of the prenatal manifestations of Basal Cell Nevus Syndrome.

Neuroimaging appearance of hypothalamic hamartomas in monozygotic twins with Pallister-Hall syndrome: case report and review of the literature.

BACKGROUND: Pallister-Hall syndrome (OMIM #146510) is a rare autosomal dominant condition caused by a mutation in the GLI3 gene. The cardinal feature of Pallister-Hall syndrome is the presence of hypothalamic hamartomas, which may manifest with seizures, panhypopituitarism and visual impairment. In Pallister-Hall syndrome, dysplastic histogenetic processes responsible for hypothalamic hamartomas are thought to disrupt early craniofacial development. The clinical presentation of Pallister-Hall syndrome may include: characteristic facies (low-set and posteriorly angulated ears, short nose with flat nasal bridge), cleft palate and uvula, bifid epiglottis and laryngotracheal cleft, limb anomalies (e.g., polysyndactyly, short limbs and nail dysplasia), anal atresia, genitourinary abnormalities and congenital heart defects. CASE PRESENTATION: We report the case of two monochorionic diamniotic twins diagnosed with Pallister-Hall syndrome during the neonatal period, after the identification of a hypothalamic hamartoma on day 1 by cerebral ultrasound scan, later confirmed by brain magnetic resonance imaging. Cerebral ultrasound and magnetic resonance imaging presentations were identical in both twins. DISCUSSION AND CONCLUSIONS: We review previously published cases (four reports) of hypothalamic hamartomas identified via cerebral ultrasound and compare reported ultrasonographic features. Main differential diagnoses based on cerebral ultrasound findings are discussed. Full description of typical magnetic resonance imaging appearance is also provided. This is the first case reported in the literature of monochorionic diamniotic twins affected by genetically confirmed Pallister-Hall syndrome with identical hypothalamic hamartomas at cerebral ultrasound and magnetic resonance imaging. Moreover, this paper adds to the existing literature on the sonographic appearance of hypothalamic hamartomas. Considering the consistency in hypothalamic hamartomas' sonographic appearance, we support the use of cerebral ultrasound as a first-line neuroimaging modality in case of clinical suspicion of Pallister-Hall syndrome.

Evaluation of the Efficacy of a Hydrolyzed Collagen Supplement for Improving Skin Moisturization, Smoothness, and Wrinkles.

Objective: We sought to assess the efficacy of a hydrolyzed collagen supplement (Lapi Gelatine, Empoli, Italy) for improving skin moisturization and elasticity as well as the appearance of wrinkles. Methods: A monocentric, randomized, controlled study was performed; the study included 52 volunteers who were divided into two groups. Twenty-six subjects took the collagen supplement and the other 26 participants received maltodextrin for a period of 56 days. Skin moisturization, skin elasticity, and wrinkle depth were instrumentally evaluated. Clinical parameters, including skin softness, skin firmness, skin smoothness, and the visibility of wrinkles were subjectively evaluated by a dermatologist. Finally, the gastrointestinal tolerability was evaluated during the period of treatment. Results: Improvements in skin moisturization, skin elasticity and wrinkle depth were measured in the participants taking the hydrolyzed collagen after 28 days. In all enrolled participants, the results of the analysis of variance showed a statistically significant effect of the interaction between product and time. The evolution over time of the investigated parameters was significantly different between the participants taking the hydrolyzed collagen and the participants taking the maltodextrin. Furthermore, it was well tolerated and no adverse effects were recorded.

Smith-Magenis Syndrome-Clinical Review, Biological Background and Related Disorders.

Smith-Magenis syndrome (SMS) is a complex genetic disorder characterized by distinctive physical features, developmental delay, cognitive impairment, and a typical behavioral phenotype. SMS is caused by interstitial 17p11.2 deletions (90%), encompassing multiple genes and including the retinoic acid-induced 1 gene (RAI1), or by pathogenic variants in RAI1 itself (10%). RAI1 is a dosage-sensitive gene expressed in many tissues and acting as transcriptional regulator. The majority of individuals exhibit a mild-to-moderate range of intellectual disability. The behavioral phenotype includes significant sleep disturbance, stereotypes, maladaptive and self-injurious behaviors. In this review, we summarize current clinical knowledge and therapeutic approaches. We further discuss the common biological background shared with other conditions commonly retained in differential diagnosis.