Cardiac function in adolescents and young adults with 22q11.2 deletion syndrome without congenital heart disease.

BACKGROUND: Diagnosis and treatment of 22q11.2 deletion syndrome (22q11.2DS) have led to improved life expectancy and achievement of adulthood. Limited data on long-term outcomes reported an increased risk of premature death for cardiovascular causes, even without congenital heart disease (CHD). The aim of this study was to assess the cardiac function in adolescents and young adults with 22q11.2DS without CHDs. METHODS: A total of 32 patients (20M, 12F; mean age 26.00 ± 8.08 years) and a healthy control group underwent transthoracic echocardiography, including Tissue Doppler Imaging (TDI) and 2-dimensional Speckle Tracking Echocardiography (2D-STE). RESULTS: Compared to controls, 22q11.2DS patients showed a significant increase of the left ventricle (LV) diastolic and systolic diameters (p = 0.029 and p = 0.035 respectively), interventricular septum thickness (p = 0.005), LV mass index (p < 0.001) and aortic root size (p < 0.001). 2D-STE analysis revealed a significant reduction of LV global longitudinal strain (p < 0.001) in 22q11.2DS than controls. Moreover, several LV diastolic parameters were significantly different between groups. CONCLUSIONS: Our results suggest that an echocardiographic follow-up in 22q11.2DS patients without CHDs can help to identify subclinical impairment of the LV and evaluate a potential progression of aortic root dilation over time, improving outcomes, reducing long-term complications and allowing for a better prognosis.

The impact of National Containment Measures on a Pediatric Italian regional Hub for COVID-19, an observational study.

BACKGROUND: Numerous studies described the epidemiological link and main clinical features of pediatric COVID-19, during the first pandemic period. Our study encompasses several different phases since the National Lockdown in Italy. The primary outcome is (I) to analyze the prevalence of positive NST (Nasopharyngeal Swab Test) among the largest Italian Pediatric cohort admitted to a single regional PED Hub for COVID-19 during an eight-month period. Secondary outcomes are: (II) the description of trend of admissions in our PED and (III) the categorization of the positive patients according to clinical manifestations and epidemiological link. METHODS: We described 316 patients with a positive NST for SARS-CoV2, on a total of 5001 nasopharyngeal swabs performed among 13,171 admissions at our PED, over a period starting from March 17th, 2020 to December 1st, 2020. Age, epidemiological link, clinical features and hospitalizations were analyzed according to different lockdown phases. Data were collected anonymously from electronic records and analyzed using SPSS 22.00 statistics software (Chicago, IL). RESULTS: Thirty-six percent of total admissions have been tested. During the post lockdown period, we performed the highest percentage of NST (Nasopharyngeal Swab Test) 49.7%, and among them 7.9% were positive. The prevalence of infection during a 10-month period was 2.3%. Mean age was 6.5 years old. Familial Link accounted for the 67.7% of infection, while Extrafamilial and Unknown link accounted for 17 and 14.9%, respectively. Familial link is predominant during all phases. Seventeen patients showed an intra-scholastic link, and the highest prevalence was observed in the 7-10 years age group, with a prevalence of 12.8% (5 patients). Fever was the most frequent symptom (66%), in particular among preschooler children aged 0-6 years (71.9%). Older children were more frequently symptomatic. Seven patients were admitted with MIS-C diagnosis. CONCLUSIONS: Different levels of containment measures caused important changes in number of positive NST for SARS-CoV2. Familial link was predominant in our cohort, during all phases of Lockdown. The risk of being infected at home is four time greater than the risk of being infected from an extra familial individual. Further studies are needed to evaluate the clear impact of intra-scholastic link. The constant improvement in knowledge on onset symptoms and risk factor for SARS-CoV2 infection and its complications (e.g. MIS-C), can impact on number of hospitalizations, ICU admissions and early management.

Myoclonic epilepsy, parkinsonism, schizophrenia and left-handedness as common neuropsychiatric features in 22q11.2 deletion syndrome.

BACKGROUND: 22q11.2 deletion syndrome (22q11.2DS) is considered as the genetic model of schizophrenia. However, its polymorphic nature has led researchers to further investigate its neuropsychiatric manifestations. METHODS: We enrolled 56 adults (38 men, 18 women) diagnosed with 22q11.2DS. All subjects were evaluated by a multidisciplinary team. The neuropsychiatric features were investigated by means of clinical and neurophysiological evaluation (video-EEG). RESULTS: Thirty per cent of our patients were left-handed. Fifty-eight per cent had a low IQ, and 22 of 56 subjects had psychotic disorders (13 of 22 with schizophrenia). Eighteen patients reported at least one seizure in their lifetime, and ten were diagnosed with epilepsy; among them, seven had genetic generalised epilepsy (GGE), and five of seven showed features suggestive of juvenile myoclonic epilepsy (JME). Video-EEG recordings revealed generalised epileptiform abnormalities in 24 of 56 cases. Besides, only one patient with epilepsy had a cardiac malformation. Lastly, 31 of 56 subjects presented with parkinsonism, 16 of whom were taking neuroleptics. None of the 15 patients with parkinsonism not related to neuroleptic therapy was diagnosed with epilepsy, compared with 6 of those taking antipsychotics. CONCLUSIONS: 22q11.2DS is characterised by left-handedness and neuropsychiatric features such as cognitive impairment, schizophrenia, epilepsy and parkinsonism. GGE, mostly the JME phenotype, is the predominant epilepsy type. The significant association between 22q11.2DS and parkinsonian features confirms these patients' genetic susceptibility to parkinsonism. Despite the lack of any conclusive evidence, our study suggests a possible relationship between the analysed clinical variables: (1) an inverse correlation between low IQ/psychosis/epilepsy and major cardiac diseases; (2) a direct association between psychosis and both mental delay and epilepsy; and (3) an inverse correlation between parkinsonism and epilepsy.

Left pulmonary artery in 22q11.2 deletion syndrome. Echocardiographic evaluation in patients without cardiac defects and role of Tbx1 in mice.

INTRODUCTION AND HYPOTHESIS: Patients with 22q11 deletion syndrome (22q11.2DS) present, in about 75% of cases, typical patterns of cardiac defects, with a particular involvement on the ventricular outflow tract and great arteries. However, in this genetic condition the dimensions of the pulmonary arteries (PAs) never were specifically evaluated. We measured both PAs diameter in patients with 22q11.2DS without cardiac defects, comparing these data to a normal control group. Moreover, we measured the PAs diameter in Tbx1 mutant mice. Finally, a cell fate mapping in Tbx1 mutants was used to study the expression of this gene in the morphogenesis of PAs. METHODS: We evaluated 58 patients with 22q11.2DS without cardiac defects. The control group consisted of 54 healthy subjects, matched for age and sex. All cases underwent a complete transthoracic echocardiography. Moreover, we crossed Tbx1+/- mice and harvested fetuses. We examined the cardiovascular phenotype of 8 wild type (WT), 37 heterozygous (Tbx1+/-) and 6 null fetuses (Tbx1-/-). Finally, we crossed Tbx1Cre/+mice with R26RmT-mG Cre reporter mice to study Tbx1 expression in the pulmonary arteries. RESULTS: The echocardiographic study showed that the mean of the LPA/RPA ratio in 22q11.2DS was smaller (0.80 ± 0.12) than in controls (0.97 ± 0.08; p < 0.0001). Mouse studies resulted in similar data as the size of LPA and RPA was not significantly different in WT embryos, but in Tbx1+/- and Tbx1-/- embryos the LPA was significantly smaller than the RPA in both mutants (P = 0.0016 and 0.0043, respectively). We found that Tbx1 is expressed near the origin of the PAs and in their adventitia. CONCLUSIONS: Children with 22q11.2DS without cardiac defects show smaller LPA compared with healthy subjects. Mouse studies suggest that this anomaly is due to haploinsufficiency of Tbx1. These data may be useful in the clinical management of children with 22q11.2DS and should guide further experimental studies as to the mechanisms underlying PAs development.

Congenital heart diseases and cardiovascular abnormalities in 22q11.2 deletion syndrome: From well-established knowledge to new frontiers.

Congenital heart diseases (CHDs) and cardiovascular abnormalities are one of the pillars of clinical diagnosis of 22q11.2 deletion syndrome (22q11.2DS) and still represent the main cause of mortality in the affected children. In the past 30 years, much progress has been made in describing the anatomical patterns of CHD, in improving their diagnosis, medical treatment, and surgical procedures for these conditions, as well as in understanding the underlying genetic and developmental mechanisms. However, further studies are still needed to better determine the true prevalence of CHDs in 22q11.2DS, including data from prenatal studies and on the adult population, to further clarify the genetic mechanisms behind the high variability of phenotypic expression of 22q11.2DS, and to fully understand the mechanism responsible for the increased postoperative morbidity and for the premature death of these patients. Moreover, the increased life expectancy of persons with 22q11.2DS allowed the expansion of the adult population that poses new challenges for clinicians such as acquired cardiovascular problems and complexity related to multisystemic comorbidity. In this review, we provide a comprehensive review of the existing literature about 22q11.2DS in order to summarize the knowledge gained in the past years of clinical experience and research, as well as to identify the remaining gaps in comprehension of this syndrome and the possible future research directions.

Effects of Exercise on Arrhythmia (and Viceversa): Lesson from the Greek Mythology.

Exercise represents an important lifestyle factor in all human ages when felt in harmony with other psycho-physical and environmental variables that affect individual life (e. g. quality of interest, affections, environment, diet and food). Consequently, in addition to the training level, the amount, intensity and modality of exercise (ana-/aerobic, isometric/isotonic), need to be personalized, considering the underlying diseases, which may benefit from it or worsening.Greek mythology gives us good examples of the exercise concept's evolution.From Discus-thrower to Spear-carrier the idea of physical activity is more effectively expressed. The Myron Discobolus displays the enduring pattern of athletic energy translated into the dynamic force given by the exercise. In Doryphoros instead, the physical activity is oriented to the achievement of the required psyco-physical harmony, who's the concept is aimed of being expressed by the sculpture.As outlined below, even in the field of arrhythmia, scientific evidence as well as clinical experience, supports the same concept: physical activity may be important while safely managed and personalized.

Effects of inhaled hypertonic (7%) saline on lung function test in preschool children with cystic fibrosis: results of a crossover, randomized clinical trial.

BACKGROUND: This crossover, randomized, double-blind study (conducted over a 32-week period) was performed to determine, in clinically stable Cystic fibrosis (CF) preschool children: the effects of 7% inhaled hypertonic saline on spirometry and interrupter resistance technique (Rint), and the possible side effects. METHODS: Twelve CF children (6M, mean age ± SD: 5.7 ± 0.8 yrs) were enrolled and randomly assigned to receive hypertonic saline (HS-4 ml 7% sodium chloride), or normal saline (NS-0.9% sodium chloride) twice a day. After a 16 weeks period, therapy was exchanged to allow all the patients enrolled in the study to carry out both treatments. Monitoring visits, spirometry (COSMED Quark PFT4 ergo) and Rint were scheduled at 0,4,16,20,32 weeks. At T0, spirometric measurements and Rint were performed immediately before and 30 min after the inhalation therapy. Salbutamol (400 mcg) was administered before the drug at each visit. RESULTS: After a 16-weeks treatment with HS an improvement of FVC (p = 0.02) and a favorable trend of FEV1 were registered. A worsening of FEV1 (p < 0.0001) and of FEF25-75 (p = 0.019) were found in NS group. No differences were found in expiratory and inspiratory Rint in both groups. No serious adverse events occurred. CONCLUSIONS: Seven percent hypertonic saline therapy proved to be a useful and safe treatment in young CF children with clinically stable conditions. TRIAL REGISTRATION: ISRCTN12345678 .

Cardiorespiratory fitness and sports activities in children and adolescents with solitary functioning kidney.

BACKGROUND: An increasing number of children with chronic disease require a complete medical examination to be able to practice physical activity. Particularly children with solitary functioning kidney (SFK) need an accurate functional evaluation to perform sports activities safely. The aim of our study was to evaluate the influence of regular physical activity on the cardiorespiratory function of children with solitary functioning kidney. METHOD: Twenty-nine patients with congenital SFK, mean age 13.9 ± 5.0 years, and 36 controls (C), mean age 13.8 ± 3.7 years, underwent a cardiorespiratory assessment with spirometry and maximal cardiopulmonary exercise testing. All subjects were divided in two groups: sedentary (S) and trained (T) patients, by means of a standardized questionnaire about their weekly physical activity. RESULTS: We found that mean values of maximal oxygen consumption (VO2max) and exercise time (ET) were higher in T subjects than in S subjects. Particularly SFK-T presented mean values of VO2max similar to C-T and significantly higher than C-S (SFK-T: 44.7 ± 6.3 vs C-S: 37.8 ± 3.7 ml/min/kg; p < 0.0008). We also found significantly higher mean values of ET (minutes) in minutes in SFK-T than C-S subjects (SFK-T: 12.9 ± 1.6 vs C-S: 10.8 ± 2.5 min; p <0.02). CONCLUSION: Our study showed that regular moderate/high level of physical activity improve aerobic capacity (VO2max) and exercise tolerance in congenital SFK patients without increasing the risks for cardiovascular accidents and accordingly sports activities should be strongly encouraged in SFK patients to maximize health benefits.

Congenital myxoid and pigmented dermatofibrosarcoma protuberans: a case report.

Dermatofibrosarcoma protuberans (DFSP) is a low-grade, mesenchymal, spindle cell tumor. In addition to the classical form characterized by a storiform pattern of tumor cells, pigmented (Bednar's tumor) and myxoid variants can be observed. Classical DFSP and Bednar's tumor are easily diagnosed. The myxoid variant represents a diagnostic challenge. Pigmented and myxoid variants are rare and thus far have never been reported in association in congenital DFSP. We came across a unique DFSP that was, at the same time, congenital, pigmented, and myxoid. The tumor was surgically excised with broad free margins and no recurrence. The differential diagnosis with other entities such as giant cell fibroblastoma, CD34-positive plaque-like dermal fibroma, superficial plaque-like CD34 DFSP, and neurocristic hamartoma is discussed. The recognition of this hybrid variant of congenital DFSP is important to avoid under- or overtreatment.