EMILIN1 deficiency causes arterial tortuosity with osteopenia and connects impaired elastogenesis with defective collagen fibrillogenesis.

EMILIN1 (elastin-microfibril-interface-located-protein-1) is a structural component of the elastic fiber network and localizes to the interface between the fibrillin microfibril scaffold and the elastin core. How EMILIN1 contributes to connective tissue integrity is not fully understood. Here, we report bi-allelic EMILIN1 loss-of-function variants causative for an entity combining cutis laxa, arterial tortuosity, aneurysm formation, and bone fragility, resembling autosomal-recessive cutis laxa type 1B, due to EFEMP2 (FBLN4) deficiency. In both humans and mice, absence of EMILIN1 impairs EFEMP2 extracellular matrix deposition and LOX activity resulting in impaired elastogenesis, reduced collagen crosslinking, and aberrant growth factor signaling. Collagen fiber ultrastructure and histopathology in EMILIN1- or EFEMP2-deficient skin and aorta corroborate these findings and murine Emilin1-/- femora show abnormal trabecular bone formation and strength. Altogether, EMILIN1 connects elastic fiber network with collagen fibril formation, relevant for both bone and vascular tissue homeostasis.

Revealing Mitral Valve Cleft Using Real-Time 3-Dimensional Echocardiography in Children with Mitral Regurgitation.

Mitral valve cleft (MVC) is the most common cause of congenital mitral regurgitation (MR). MVC may be located on the anterior or posterior leaflets. We evaluated children with moderate-to-severe MR using 3D transthoracic echocardiography (3DTTE) to diagnose MVC and determine the location, shape and size of MVC. Twenty-one patients under 18 years of age with moderate-to-severe MR without symptoms who were suspected of having MVC were included in the study. The patients' history and clinical data were obtained from the medical records. 2D and 3D imaging were performed with a high-quality machine (EPIQ CVx). A vena contracta (VC) of colour Doppler regurgitated jet 3-7 and ≥ 7 mm defined moderate-to-severe regurgitation. An isolated anterior leaflet cleft (ALC) was detected in four patients, an isolated posterior leaflet cleft (PLC) in 12 patients, and both an ALC and PLC in five patients. VC was larger in patients with ALCs than PLCs (8.85 mm vs. 6.64 mm). Global LV longitudinal strain was better in the ALC group than in the PLC and both-posterior-and anterior MVC groups (- 24.7, - 24.3, and - 24%, respectively). Global circumferential strain was better in the ALC group (- 28.9%) and reduced in the bi-leaflet MVC group (- 28.6%). 3DTTE for visualisation of the MV can be successfully implemented in children and should be proposed during follow-up. AMVC and bi-leaflet MVC results in severe regurgitation and bi-leaflet MVC may be the reason for systolic dysfunction determined before clinically proven symptoms in the future.

Pediatric Primary Raynaud's Phenomenon: A Comprehensive Cardiovascular Analysis.

Our aim in this study is to evaluate the cardiovascular findings of pediatric patients with primary Raynaud's phenomenon (RP) and to determine if there are any pathological findings. Our study included 42 pediatric patients aged between 7 and 18 who were diagnosed with primary RP and did not have any additional underlying structural vascular disease or secondary rheumatological conditions. The control group consisted of 30 healthy volunteers aged 7-18 years, matched by age and sex, without any additional diseases. We evaluated demographic, clinical, and laboratory findings, echocardiographic and capillaroscopic features, as well as carotid intima-media thickness. Compared to the control group, pediatric patients with primary RP showed increased A wave velocity and E/E' ratio parameters in the left ventricle, indicating diastolic dysfunction of the heart. The isovolumetric relaxation time (IVRT) was prolonged in both the left and right ventricles, and the E/A ratio decreased in the left ventricle. The myocardial performance index (MPI), indicating both systolic and diastolic dysfunction, increased in both ventricles. Additionally, the aortic stiffness index, aortic elastic modulus (Ep), and left carotid intima-media thickness (CIMT) significantly increased, while distensibility decreased in pediatric patients with primary RP compared to the control group. The cardiovascular evaluation of pediatric patients with primary RP revealed that diastolic dysfunction is likely present in both the left and right heart. Additionally, based on the aorta and carotid intima measurements, it is suggested that pediatric patients with primary RP are at risk for developing atherosclerosis.

Perinatal outcomes following early prenatal diagnosis: insights from a single-center experience with Ebstein anomaly and tricuspid valve dysplasia.

PURPOSE: Ebstein anomaly (EA) and tricuspid valve dysplasia (TVD) represent uncommon congenital malformations of the tricuspid valve. The purpose of this study is to report on current perinatal outcomes of EA/TVD in our center and to investigate clinical and fetal echocardiographic predictors of perinatal mortality. METHODS AND RESULTS: We performed a retrospective study among fetuses diagnosed from January 2014 to December 2023. Clinical and echocardiographic data were obtained from hospital records of Research and Education Hospital. The primary outcome was perinatal mortality. Of 21 fetuses diagnosed, there were 1 lost to follow-up, 1 termination, and 7 demises. In the live-born cohort of 12 live-born patients, 2 died before discharge, yielding an overall perinatal mortality of 50%. The median gestational age at diagnosis was 23 for non-survivors and 24 weeks for survivors. Birth weight was lower in non-survivors (2430 g vs 2990 g). Tricuspid insufficiency severity varied insignificantly. Non-survivors exhibited higher rates of hydrops, functional atresia, and absent antegrade flow (p < 0.05). Two infants with severe tricuspid insufficiency and congenital abnormalities died postnatally. The limited dataset enables further analysis for a predictive model. Notably, all non-survivors displayed hydrops, functional atresia, and absent antegrade flow, hindering definitive determination of the most impactful parameter on survival estimation. CONCLUSION: Perinatal mortality remains notably elevated in fetuses with EA/TVD. The individuals at the highest risk are those with antegrade flow loss and functional atresia of pulmonary valve, this high-risk subgroup could benefit from targeted interventions, such as novel prenatal therapies or a more comprehensive perinatal approach involving optimized timing of delivery and postnatal interventional strategies.

Fetal left ventricular myocardial performance index measured at 11-14 weeks of gestation in fetuses with an increased nuchal translucency.

OBJECTIVE: This study aimed to evaluate the effect of an increase in nuchal translucency (NT) thickness on the myocardial performance index (MPI) in fetuses without cardiac anomaly in the first trimester and to determine whether a difference in MPI between those with and without trisomy 21 in these fetuses could be determined. METHODS: The study group consisted of 53 pregnancies complicated with increased NT thickness without any associated structural anomalies. Forty-six gestational age-matched pregnant women whose fetuses had normal NT thickness were enrolled as the control group. RESULTS: In the increased NT thickness group, the mean isovolumetric relaxation time (IRT) value (0.050 ± 0.011 s) was significantly higher and the mean ejection time (ET) value (0.149 ± 0.010 s) was significantly lower than those values in the normal NT thickness group (0.045 ± 0.005 and 0.155 ± 0.009 s, p = 0.023 and p = 0.009, respectively). We found a significantly higher mean left MPI value in the increased NT thickness group (0.574 ± 0.153) versus the normal NT thickness group (0.487 ± 0.107, p < 0.001). Within the increased NT thickness group, the mean left MPI value was similar in the fetuses with normal karyotype and those with trisomy 21 (p = 0.419). CONCLUSION: We demonstrated a significantly greater mean MPI value in the increased NT thickness group than in the normal NT thickness group. Within the increased NT thickness group, no differences in the left MPI value in the fetuses with normal karyotype and the fetuses with trisomy 21 were found.

Early Hemodynamic Effects of Mydriatic Eye Drops in Preterm Infants.

OBJECTIVE: Mydriatic eye drops used for retinopathy of prematurity (ROP) examination can cause systemic effects, and there are case reports of serious adverse effects in the literature. In this prospective study, we aimed to evaluate the early hemodynamic effects of mydriatic eye drops to understand the possible mechanisms of adverse effects. STUDY DESIGN: Between December 2018 and March 2019, preterm babies less than 32 gestational weeks and who underwent ophthalmologic examination in our unit were included. The vital signs (heart rate, respiratory rate, oxygen saturation [SpO2], and blood pressure values), cerebral and mesenteric tissue saturation by near-infrared spectroscopy (NIRS), and left ventricular functions of infants were recorded before and after applying mydriatic eye drops (2.5% phenylephrine and 0.5% tropicamide). The data were compared statistically. Strict adherence to prevent systemic absorption of the eye drops was applied. RESULTS: Thirty-two mydriasis procedures were evaluated in 26 patients. The mean gestational age was 28.5 ± 1.7 weeks, and the mean birth weight was 943 ± 233 g. There were no significant differences in terms of vital signs of infants including heart rate, blood pressure, and oxygen saturation [SpO2] levels before and after eye-drop application. In addition, NIRS values showed no significant differences between before and after measurements. No significant differences were detected at echocardiographic evaluation performed before and after mydriatic administration. No adverse reaction was observed in the study population during the study. CONCLUSION: This is the first study that evaluated the early hemodynamic effects of mydriatic eye drops used for ROP screening by vital signs, NIRS, and echocardiographic evaluation. Mydriatic eye drops have no significant effect on early hemodynamic parameters including vital signs, NIRS, and echocardiographic findings in preterm infants. We suggest that a cautious approach for avoiding the systemic absorption of these agents may prevent the possible early systemic effects in this high-risk population. KEY POINTS: · Mydriatic eye drops are commonly used for pupil dilatation before retinopathy of prematurity examination, and there are reports of serious adverse events caused by these drops.. · Due to the adverse events of eye drops, hemodynamic effects of these agents were investigated by clinical findings, near-infrared spectroscopy, and echocardiography.. · No significant early hemodynamic effect was observed so avoiding systemic effects may be prevented with precautions..

Prenatal diagnosis and postnatal outcomes of right aortic arch anomalies.

PURPOSE: To give a report on the experience of our tertiary perinatology clinic on the pre- and postnatal management of the right aortic arch (RAA) by evaluating the patients as isolated and non-isolated RAA. MATERIALS AND METHODS: Patients referred to our perinatology clinic for fetal echocardiography were evaluated retrospectively. They were assessed in two groups: isolated RAA and non-isolated RAA. The isolated RAA group consisted of patients without any additional cardiac or extracardiac anomalies. According to our routine practice, all patients received detailed prenatal ultrasonography following fetal echocardiography and genetic counseling. RESULTS: A total of 60 patients were evaluated. 38 patients (63.3%) presented with additional cardiac anomalies. 21.7% had extracardiac anomalies, including 16.7% who also had cardiac anomalies. In 2 patients (3.7%) 22q11.2 microdeletion, in 2 patients (3.7%) trisomy 21, in 1 patient (1.9%) trisomy 13 and in 1 patient (1.9%) 20p12.1p11.23 (a deletion of 2880 kbp) were reported. The most common cardiac anomaly associated with RAA was Tetralogy of Fallot (25%). Fetal growth restriction was reported in 8.3% of the cases. 18 patients had isolated RAA. 16 out of the 18 patients had normal genetic analysis. 2 of them (11.11%) presented with a 22q11.2 microdeletion. CONCLUSION: A single-center experience on the diagnosis and management of RAA has been reported in this study. The results indicate that a prenatal cardiac evaluation in 3VV is of utmost importance in all pregnancies to detect RAA and refer these patients to the appropriate perinatology clinics for further evaluation and care.

An integrated clinical and molecular study of a cohort of Turkish patients with Marfan syndrome harboring known and novel FBN1 variants.

Marfan syndrome (MFS) is an autosomal dominant genetic condition that mainly affects connective tissue in many parts of the body. Cardinal manifestations involve the ocular, skeletal, and cardiovascular systems. The diagnosis of MFS relies on the revised Ghent criteria, outlined by international expert opinion to facilitate accurate recognition of this syndrome as well as to improve patient management and counseling. However, it may not always be possible to make a definitive diagnosis according to these criteria in each patient and thus molecular confirmation is necessary in subjects with suspected MFS. This debilitating, if not fatal, disorder is caused by mutations in FBN1, which encodes a major constitutive element of extracellular microfibrils. Here, we present a detailed clinical and molecular analysis of 76 Turkish patients with definitive or suspected MFS diagnosed at our center between 2014 and 2019. We were able to identify a total of 51 different FBN1 variants in our cohort, 31 of which have previously been reported in the relevant scientific literature. The remaining 20 variants have not been documented to date. In one patient, we detected a large deletion including the entire FBN1 gene using the array CGH approach. Currently, there are very few studies on the genotype-phenotype correlation of patients with MFS, and no clear genotype-phenotype maps for MFS have been constructed so far, except for some cases. We believe that our findings will make a rich and peculiar contribution to the elusive genotype-phenotype relationship in MFS, especially in this large and populous ethnic group.

Prenatal Diagnosis of Double Aortic Arch: Associated Findings and Postnatal Clinical Outcomes.

OBJECTIVES: The aim of this study is to share our experience in the prenatal diagnosis and characteristics of double aortic arc and neonatal consequences. METHODS: We retrospectively analyzed 2153 fetal echocardiography reports between 2014 and 2019 years. Records of 14 fetuses with double aortic arc were examined. Prenatal and postnatal medical records, sonographic images, genetic reports, associated cardiac and extracardiac anomalies, and neonatal clinical results of affected fetuses were reviewed retrospectively. RESULTS: DAA was isolated in 9 of 14 (64.2%) cases, while the other five cases had cardiac or extracardiac accompanying ultrasound findings. Three of cases (21.4%) were associated with other heart pathologies, including ventricular septal defect, double outlet right ventricle, and persistent left superior vena cava. In 10 cases (71.43%), the right aortic arch diameter was dominant. The left aortic arc was dominant in two cases and both arcs were symmetrical in the remaining two cases. 22q11 microdeletion was the only chromosomal abnormality and was detected in two of nine patients who accepted genetic analysis. Intrauterine fetal death occurred in two of the cases. After birth, in 58.3% (7/12) of the live born cases various degrees of symptoms. Surgical repair was performed with the division of the aorta to all symptomatic cases at different times according to severity of the complaints. CONCLUSIONS: Since it can cause severe respiratory distress in the postnatal period and may accompany chromosomal anomalies, it is important to provide antenatal diagnosis of double aortic arc and adequate counseling to the family.

Prenatal diagnosis of left pulmonary artery sling and review of literature.

Left pulmonary artery sling (LPAS) is a very rare cause of large airway compression. In LPAS, the left pulmonary artery (LPA) arises from the proximal right pulmonary artery, coursing over the right mainstem bronchus, posterior to the trachea and anterior to the esophagus prior to reaching the left hilum. The aberrant course of the LPA results in anatomical obstruction of the right mainstem bronchus, the trachea, or both. Only a few reports present the prenatal features of LPAS. In this report, we present the prenatal diagnosis of a case of LPAS in one of a set of identical twins in which the only feature was that of an abnormal course of the LPA on 3-vessel tracheal view. The cross-sectional view at the level of three vessels which includes both pulmonary artery branches is useful to detect this abnormality. Color and power Doppler may be helpful as well.

Pulmonary Hypertension in Children With ß Thalassemia Major, Are Splenectomy and High-Ferritin Levels Related or Not?

We evaluated the risk of pulmonary hypertension (PH) by measuring the velocity of the tricuspid regurgitation jet velocity (TRV) on echocardiography and the associations among the TRV, ferritin, and history of splenectomy in children with ß thalassemia major (TM). In total, 85 children with TM were examined with continuous Doppler flow. Patients with an abnormal TRV (>2.5 m/s) were grouped into those with a TRV of 2.5 to 2.9 m/s and TRV>2.9 m/s. A TRV of >2.5 m/s was identified in 72; 31 (36%) of these patients had a TRV of >2.9 m/s, suggesting a risk for significant PH. The ferritin concentration was significantly higher in patients with a TRV of >2.9 m/s and showed a positive correlation with a TRV. The TRV was significantly correlated with markers of diastolic function: the tricuspid peak early diastolic wave (E) was higher in patients with a TRV of >2.9 m/s and showed a significant correlation with the TRV (R=0.315). The ratio of the TRV over the velocity-time integral (VTI) at the right ventricular outflow tract (TRV/VTI RVOT), which is correlated with the pulmonary vascular resistance, was higher in patients with a TRV of >2.9 m/s. In total, 27 patients had splenectomy. Splenectomized patients had a higher TRV and splenectomy was correlated with the TRV (R=-0.221). A risk of PH as defined by a TRV of >2.9 m/s was common in our patients with TM. Screening with Doppler flow indices on echocardiography can detect PH in early stages.

Transcatheter correction of Scimitar syndrome: occlusion of abnormal pulmonary venous drainage and vascular supply in an infant.

Treatment of Scimitar syndrome is usually surgical; however, if there is "dual drainage" - that is, one to the inferior caval vein and the other to the left atrium - it is possible to successfully treat this anomaly via a less-invasive transcatheter approach. We report a case of Scimitar syndrome in a 21-month-old, male infant successfully treated with transcatheter embolisation.

HAX-1 deficiency: Characteristics of five cases including an asymptomatic patient.

BACKGROUND: Mutations in the HAX-1 gene cause an autosomal recessive form of severe congenital neutropenia (SCN), which particularly manifests with recurrent skin, lung and deep tissue infections from the first few months of life. OBJECTIVE: We retrospectively evaluated the clinical and laboratory findings of the patients diagnosed with SCN carrying HAX1 gene mutations. METHODS: A total of five patients with SCN, carrying a HAX1 gene mutation, were evaluated in terms of clinical and laboratory findings. Mutation analysis of the candidate genes (HAX1, ELANE and CSF3R) was performed. RESULTS: All of the patients lived in Turkey; four of them were of Kurdish origin and one was Turkish. Of the five patients, three were girls and two were boys, and the mean age of the patients was 8.8 years old (range 4-15 years). The mean age of diagnosis was 25.8 months (range 2 months-5 years). The infections diagnosed included recurrent gingivitis, stomatitis, and skin and soft tissue abscesses. Developmental retardation and epilepsy were present in only one patient, whereas speech retardation was present in two. All of our patients had a HAX1 mutation, and are still alive and none of them has shown malignant transformation yet. CONCLUSION: Complete blood count should be performed and absolute neutrophil count should be evaluated in patients with recurrent severe infections. In the event that neutropenia is detected, they should be investigated in terms of SCN and mutation analysis should be performed.

Treatment of neonatal fungal infective endocarditis with recombinant tissue plasminogen: activator in a low birth weight infant case report and review of the literature.

With advances in medical sciences, an increase in survival rates of low birth weight; increased incidence in use of catheter and antibiotics, and total parenteral nutrition are reported, therefore, the rate of fungal infections in late and very late onset neonatal sepsis have increased. Although fungal endocarditis rarely occur in newborns, it has a high morbidity and mortality. Antifungal therapy is often insufficient in cases who develop fungal endocarditis and surgical treatment is not preferred due to its difficulty and high mortality. Herein, fungal endocarditis in a preterm newborn treated with single-dose recombinant tissue plasminogen activator in addition to antifungal therapy is presented and relevant literature has been reviewed. The vegetation completely disappeared following treatment and no complication was observed.

Left atrial and left ventricular strain dynamics with echocardiography in asymptomatic children with mitral regurgitation.

Left atrial (LA) dilatation is a strong predictor of cardiovascular morbidity and mortality. Strain parameters evaluating LA functions have gained importance in assessing cardiovascular health. This study aimed to investigate the relationship between LA and left ventricular (LV) strain, using speckle-tracking echocardiography, and assess the impact of vena contracta on LV functioning in asymptomatic children with mitral regurgitation. We evaluated 45 asymptomatic mitral regurgitation patients, categorized as mild, moderate, and severe. LV strain was significantly lower in the moderate group (-17.8 ± 3.7%) and further reduced in the severe group (16 ± 2.1%) compared to the reference group (20.5 ± 6.2%). Conversely, LA reservoir strain was higher in the severe and moderate groups (38 ± 12.9% and 40.7 ± 9.5%, respectively) compared to the controls (31.3 ± 7.5%; p < 0.0001). The severe group also displayed a milder depression of contraction (12.2%) compared to the moderate group (13 ± 7.2%). In the moderate and severe groups, LV strain correlated significantly with vena contracta (r=-0.858; p = 0.04), with vena contracta emerging as the only independent predictor for LV longitudinal strain. ROC curve analysis indicated a cut-off value > 5.65 mm for vena contracta, which had a positive predictive value of 75% for predicting LV function impairment. In conclusion, this study emphasizes the significance of assessing LA and ventricular strain in asymptomatic children with mitral regurgitation. Furthermore, vena contracta with diameters greater than 5.6 mm may alert clinicians to the possibility of LV function impairment. These findings offer valuable insights for the follow-up and management of paediatric patients with mitral regurgitation, enabling early detection of potential complications and improved patient outcomes.

Assessment of cardiac parameters in evaluation of cardiac functions in patients with thalassemia major.

The aim of the study was to evaluate cardiac function and early cardiac dysfunction of patients followed as thalassemia major. In this study, the authors compared 100 patients, diagnosed as thalassemia major with mean age 11.84 ± 4.35, with 60 healthy control subjects at the same age between 2008 and 2011. Early diagnosis of iron overload that may occur after repeated transfusions is important in this patient group. To detect early iron accumulation, the authors compared ferritin with the echo findings, the 24-hour Holter, and cardiac magnetic resonance imaging (MRI) T2* values in the patients of same age and sex, treated with chelators, without heart failure, nonsplenectomized, and do not differ in the presence of hepatitis C. Ferritin levels, left ventricular systolic functions (ejection fraction [EF], shortening fraction [SF]), left ventricular measurements, left ventricular diastolic functions, T2* image on cardiac magnetic resonance, heart rate variables in 24 hours, and Holter rhythm were evaluated to show the early failure of cardiac functions. In this study the authors confirmed that iron-related cardiac toxicity damages electrical activity earlier than myocardial contractility. Left ventricular diastolic diameter (LVDd), left ventricular mass (LVM), and LV systolic diameter (LVDs) levels were significantly higher in the patient group with ectopia. Patients with ectopia are the ones in whom LVM and LVDd are increased. In thalassemia major patients with ectopia, LF/HF ratio was markedly increased, QTc dispersion was clearly found higher in patients with ectopia rather than nonectopic patients. The standard deviation all normal RR interval series (SDNN) was found clearly lower in thalassemia major group with ectopia than control group because it is assumed that increase in cardiac sympathetic neuronal activity is related to exposure to chronic diastolic and systolic failure.

Importance of Coronary to Pulmonary Artery Fistulae Incidentally Detected on Echocardiography: Can We Ignore It During Childhood?

Backround: Coronary artery fistula (CAF) is an abnormal precapillary connection between a coronary artery and an adjacent structure. The incidence of CAF in children as estimated from echocardiography is 0.06-0.2%. We aimed to establish the follow up results of clinically silent CAF found incidentally by colour Doppler echocardiography. Methods: The study included patients with abnormal fistulous flow in the pulmonary artery who had been studied between 2008 and 2020. Patient demographics, clinical findings, indication for echocardiography, electrocardiographic findings at presentation, follow-up times and any fistula progress were obtained from the recorded files. Results: Among the 78,000 patients who had had an echocardiographic examination, 118 had been found by colour Doppler flow mapping to have a clinically silent CAF. The exit point of CAF was clearly visualized with colour Doppler in all patients. In most patients the CAF was located around the pulmonary valve and the bifurcation; in 76 patients, it was on the aortic side of the main pulmonary artery, 26 patients had fistulous flow through the anterior wall of the main pulmonary artery, two had the right ventricular outflow tract (RVOT) as the exit site, for 12, it was the right pulmonary artery, and for another two, the left pulmonary artery. The 118 patients had ongoing follow-up to mean 41 months. There was no spontaneous resolution of fistula. The patients were asymptomatic without intervention and with ongoing echocardiographic evidence of small CAF at the last follow-up. Conclusion: We recommend the treatment strategy for paediatric patients should be individualized according to fistula origin, size, chamber enlargement, draining site, age of the patient and cost of imaging during follow up.

Spectrum of Genetic Variants in a Cohort of 37 Laterality Defect Cases.

Laterality defects are defined by the perturbed left-right arrangement of organs in the body, occurring in a syndromal or isolated fashion. In humans, primary ciliary dyskinesia (PCD) is a frequent underlying condition of defective left-right patterning, where ciliary motility defects also result in reduced airway clearance, frequent respiratory infections, and infertility. Non-motile cilia dysfunction and dysfunction of non-ciliary genes can also result in disturbances of the left-right body axis. Despite long-lasting genetic research, identification of gene mutations responsible for left-right patterning has remained surprisingly low. Here, we used whole-exome sequencing with Copy Number Variation (CNV) analysis to delineate the underlying molecular cause in 35 mainly consanguineous families with laterality defects. We identified causative gene variants in 14 families with a majority of mutations detected in genes previously associated with PCD, including two small homozygous CNVs. None of the patients were previously clinically diagnosed with PCD, underlining the importance of genetic diagnostics for PCD diagnosis and adequate clinical management. Identified variants in non-PCD-associated genes included variants in PKD1L1 and PIFO, suggesting that dysfunction of these genes results in laterality defects in humans. Furthermore, we detected candidate variants in GJA1 and ACVR2B possibly associated with situs inversus. The low mutation detection rate of this study, in line with other previously published studies, points toward the possibility of non-coding genetic variants, putative genetic mosaicism, epigenetic, or environmental effects promoting laterality defects.

SIMPLE: A Novel Scoring System for Predicting Hemodynamically Significant Patent Ductus Arteriosus Without Echocardiographic Evaluation in Extremely Low Birth Weight Infants.

Aim: To develop a novel clinical scoring system for predicting hemodynamically significant patent ductus arteriosus (hsPDA) in extremely low birth weight (ELBW) infants. Methods: A prospective observational study was conducted among ELBW infants born in the study center during a 6-month period. Fourteen items were selected on a literature review basis and weighed by severity on an arbitrary 1-4 scale, the sum of which represented the Scoring preterm Infants for PDA cLinically without Echocardiographic evaluation (SIMPLE) score. The SIMPLE scores were compared at several time points during the first 3 days of life between two groups of patients: those with an hsPDA at echocardiography and those without. Results: A total of 48 ELBW infants were enrolled, of which 30 infants developed hsPDA. The SIMPLE scores of the infants with hsPDA were significantly greater than those of the infants who did not develop hsPDA. Cut-off SIMPLE scores that were significantly associated with detection of symptomatic hsPDA at each evaluation time point were identified. Conclusions: SIMPLE is the first scoring system that depends on the risk factors and clinical findings of ELBW infants for early prediction of hsPDA. It is simple, objective and easy to perform, and it does not require any additional tests and/or echocardiographic evaluation. We suggest that SIMPLE can be used as a screening tool for determining the need for echocardiographic evaluation in ELBW infants in order to minimize the number of unnecessary pediatric cardiology consultations.