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International Journal of Molecular... May 2024Fibrillin-1 and fibrillin-2, encoded by and , respectively, play significant roles in elastic fiber assembly, with pathogenic variants causing a diverse group of...
Fibrillin-1 and fibrillin-2, encoded by and , respectively, play significant roles in elastic fiber assembly, with pathogenic variants causing a diverse group of connective tissue disorders such as Marfan syndrome (MFS) and congenital contractural arachnodactyly (CCD). Different genomic variations may lead to heterogeneous phenotypic features and functional consequences. Recent high-throughput sequencing modalities have allowed detection of novel variants that may guide the care for patients and inform the genetic counseling for their families. We performed clinical phenotyping for two newborn infants with complex congenital heart defects. For genetic investigations, we employed next-generation sequencing strategies including whole-genome Single-Nucleotide Polymorphism (SNP) microarray for infant A with valvular insufficiency, aortic sinus dilatation, hydronephrosis, and dysmorphic features, and Trio whole-exome sequencing (WES) for infant B with dextro-transposition of the great arteries (D-TGA) and both parents. Infant A is a term male with neonatal marfanoid features, left-sided hydronephrosis, and complex congenital heart defects including tricuspid regurgitation, aortic sinus dilatation, patent foramen ovale, patent ductus arteriosus, mitral regurgitation, tricuspid regurgitation, aortic regurgitation, and pulmonary sinus dilatation. He developed severe persistent pulmonary hypertension and worsening acute hypercapnic hypoxemic respiratory failure, and subsequently expired on day of life (DOL) 10 after compassionate extubation. Cytogenomic whole-genome SNP microarray analysis revealed a deletion within the gene spanning exons 7-30, which overlapped with the exon deletion hotspot region associated with neonatal Marfan syndrome. Infant B is a term male prenatally diagnosed with isolated D-TGA. He required balloon atrial septostomy on DOL 0 and subsequent atrial switch operation, atrial septal defect repair, and patent ductus arteriosus ligation on DOL 5. Trio-WES revealed compound heterozygous c.518C>T and c.8230T>G variants in the gene. Zygosity analysis confirmed each of the variants was inherited from one of the parents who were healthy heterozygous carriers. Since his cardiac repair at birth, he has been growing and developing well without any further hospitalization. Our study highlights novel variants and signifies the phenotype-genotype association in two infants affected with complex congenital heart defects with and without dysmorphic features. These findings speak to the importance of next-generation high-throughput genomics for novel variant detection and the phenotypic variability associated with variants, particularly in the neonatal period, which may significantly impact clinical care and family counseling.
Topics: Humans; Fibrillin-1; Marfan Syndrome; Fibrillin-2; Male; Infant, Newborn; Heart Defects, Congenital; High-Throughput Nucleotide Sequencing; Female; Polymorphism, Single Nucleotide; Mutation; Genomics; Phenotype; Exome Sequencing; Adipokines
PubMed: 38791509
DOI: 10.3390/ijms25105469 -
Children (Basel, Switzerland) May 2024Ductus arteriosus closure may be delayed in preterm infants, and prostaglandin, a vasodilator, can affect ductal patency. Furosemide can increase renal prostaglandin...
Ductus arteriosus closure may be delayed in preterm infants, and prostaglandin, a vasodilator, can affect ductal patency. Furosemide can increase renal prostaglandin synthesis, so its net effect on patent ductus arteriosus (PDA) is uncertain. Our goal is to explore the relationship between furosemide and spontaneous ductal closure in very-low-birth-weight preterm infants. Our treatment for PDA involves fluid restriction initially and furosemide administration for hemodynamically significant PDA until closure is confirmed by the echocardiogram. We enrolled 105 infants from 1 January 2019 to 30 June 2022 and evaluated the impact of furosemide on ductal closure, including exposure duration and cumulative dose. There is no correlation between furosemide exposure and spontaneous ductal closure ( = 0.384). Furosemide exposure does not delay the postmenstrual age at which spontaneous ductal closure occurs ( = 0.558). The time for spontaneous ductal closure is positively associated with furosemide prescription days (coefficient value = 0.547, = 0.026) and negatively with gestational age (coefficient value = -0.384, = 0.062). The prescription of furosemide does not impact the probability or time duration of ductus arteriosus spontaneous closure. The cumulative dose of furosemide has minimal impact on ductal closure. The correlation between furosemide exposure duration and ductal patency duration is likely due to our treatment protocol, with gestational age being a significant factor.
PubMed: 38790605
DOI: 10.3390/children11050610 -
Journal of Cardiovascular Development... Apr 2024(1) Background: To identify reasons for the persistence of surgical ligation of the patent ductus arteriosus (PDA) in premature infants after the 2019 Food and Drug...
Who Still Gets Ligated? Reasons for Persistence of Surgical Ligation of the Patent Ductus Arteriosus Following Availability of Transcatheter Device Occlusion for Premature Neonates.
(1) Background: To identify reasons for the persistence of surgical ligation of the patent ductus arteriosus (PDA) in premature infants after the 2019 Food and Drug Administration (FDA) approval of transcatheter device closure; (2) Methods: We performed a 10-year (2014-2023) single-institution retrospective study of premature infants (<37 weeks) and compared clinical characteristics and neonatal morbidities between neonates that underwent surgical ligation before (epoch 1) and after (epoch 2) FDA approval of transcatheter closure; (3) Results: We identified 120 premature infants that underwent surgical ligation ( = 94 before, = 26 after FDA approval). Unfavorable PDA morphology, active infection, and recent abdominal pathology were the most common reasons for surgical ligation over device occlusion in epoch 2. There were no differences in demographics, age at closure, or outcomes between infants who received surgical ligation in the two epochs; (4) Conclusions: Despite increasing trends for transcatheter PDA closure in premature infants, surgical ligation persists due to unfavorable ductal morphology, active infection, or abdominal pathology.
PubMed: 38786954
DOI: 10.3390/jcdd11050132 -
Journal of Orthopaedic Case Reports May 2024Neonatal compartment syndrome is a rare phenomenon with a limited number of cases reported in the literature with varying etiologies. Current literature categorizes...
INTRODUCTION
Neonatal compartment syndrome is a rare phenomenon with a limited number of cases reported in the literature with varying etiologies. Current literature categorizes etiologies as either intrinsic or extrinsic. To the best of our knowledge, difficult delivery and delivery through vacuum are the only two iatrogenic etiologies that have been reported in the literature. Thus, this may be the first reported case of neonatal compartment syndrome secondary to a failed peripherally inserted central catheter (PICC) insertion.
CASE REPORT
We present a case of a pre-mature neonate with diffuse discoloration, paralysis, and loss of palpable pulses of the right upper extremity after a failed PICC insertion. The clinical features led to a diagnosis of compartment syndrome. Interventions were not carried out due to the pre-maturity and instability of the patient. The patient passed away at 38 days of age due to refractory hypotension and patent ductus arteriosus.
CONCLUSION
We present a case of neonatal compartment syndrome caused by a previously unreported etiology, highlighting the current dearth of knowledge. Clinicians should be aware of the unique clinical presentation of neonatal compartment syndrome and maintain high suspicion even without an obvious etiology.
PubMed: 38784880
DOI: 10.13107/jocr.2024.v14.i05.4458 -
JACC. Case Reports Apr 2024We present a 41-year-old female with progressive shortness of breath immediately after moving to sea level from high altitude. The patient was found to have a large PDA...
We present a 41-year-old female with progressive shortness of breath immediately after moving to sea level from high altitude. The patient was found to have a large PDA with systemic RV and PA pressures and pulmonary hypertension, which resolved following PDA closure.
PubMed: 38774805
DOI: 10.1016/j.jaccas.2024.102262 -
BMC Medical Genomics May 2024Thoracic aortic aneurysm/dissection (TAAD) and patent ductus arteriosus (PDA) are serious autosomal-dominant diseases affecting the cardiovascular system. They are...
BACKGROUND
Thoracic aortic aneurysm/dissection (TAAD) and patent ductus arteriosus (PDA) are serious autosomal-dominant diseases affecting the cardiovascular system. They are mainly caused by variants in the MYH11 gene, which encodes the heavy chain of myosin 11. The aim of this study was to evaluate the genotype-phenotype correlation of MYH11 from a distinctive perspective based on a pair of monozygotic twins.
METHODS
The detailed phenotypic characteristics of the monozygotic twins from the early fetal stage to the infancy stage were traced and compared with each other and with those of previously documented cases. Whole-exome and Sanger sequencing techniques were used to identify and validate the candidate variants, facilitating the analysis of the genotype-phenotype correlation of MYH11.
RESULTS
The monozygotic twins were premature and presented with PDA, pulmonary hypoplasia, and pulmonary hypertension. The proband developed heart and brain abnormalities during the fetal stage and died at 18 days after birth, whereas his sibling was discharged after being cured and developed normally post follow-up. A novel variant c.766 A > G p. (Ile256Val) in MYH11 (NM_002474.2) was identified in the monozygotic twins and classified as a likely pathogenic variant according to the American College of Medical Genetics/Association for Molecular Pathology guidelines. Reviewing the reported cases (n = 102) showed that the penetrance of MYH11 was 82.35%, and the most common feature was TAAD (41.18%), followed by PDA (22.55%), compound TAAD and PDA (9.80%), and other vascular abnormalities (8.82%). The constituent ratios of null variants among the cases with TAAD (8.60%), PDA (43.8%), or compound TAAD and PDA (28.6%) were significantly different (P = 0.01). Further pairwise comparison of the ratios among these groups showed that there were significant differences between the TAAD and PDA groups (P = 0.006).
CONCLUSION
This study expands the mutational spectrum of MYH11 and provides new insights into the genotype-phenotype correlation of MYH11 based on the monozygotic twins with variable clinical features and outcomes, indicating that cryptic modifiers and complex mechanisms beside the genetic variants may be involved in the condition.
Topics: Humans; Twins, Monozygotic; Myosin Heavy Chains; Male; Genetic Association Studies; Infant, Newborn; Phenotype; Cardiac Myosins; Aortic Aneurysm, Thoracic; Ductus Arteriosus, Patent; Female; Mutation; Aortic Dissection
PubMed: 38773466
DOI: 10.1186/s12920-024-01908-5 -
Pediatric Pulmonology May 2024A 17-year-old male presented to our hospital from an external center with complaints of chest pain and shortness of breath, referred with preliminary diagnoses of...
A 17-year-old male presented to our hospital from an external center with complaints of chest pain and shortness of breath, referred with preliminary diagnoses of pulmonary stenosis and pulmonary artery dilation. Echocardiography revealed moderate pulmonary regurgitation and mild pulmonary stenosis. Coronary computed tomography (CT) angiography showed normal coronary arteries and no presence of a patent ductus arteriosus, but an aneurysmal dilation of up to 4 cm was observed in the pulmonary artery. The patient was found to have a quadricuspid (QPV) pulmonary valve, while the aortic valve appeared normal. No phenotypic anomalies or accompanying aortic or lung abnormalities were detected in this case. Our case represents the first in the pediatric age group diagnosed via CT scan. Our study contributes insights into the relationship between QPV anomaly and pulmonary artery aneurysm, aiding in the diagnosis and management of these rare conditions. Furthermore, our findings highlight the importance of evaluating the possibility of QPV in patients with pulmonary valve stenosis, regurgitation, or artery aneurysm, emphasizing the significance of coronary CT angiography in the diagnostic process.
PubMed: 38771205
DOI: 10.1002/ppul.27070 -
Cureus Apr 2024Tricuspid atresia, a critical congenital heart defect (CHD), accounts for approximately 1% of all cases of CHDs. When tricuspid atresia is coupled with numerous other...
Tricuspid atresia, a critical congenital heart defect (CHD), accounts for approximately 1% of all cases of CHDs. When tricuspid atresia is coupled with numerous other unexpected congenital cardiac anomalies, a patient's condition becomes more serious and more complex. We present a case that demonstrates the stepwise approach to the holistic treatment of congenital tricuspid atresia in the presence of normally related great vessels, a large ventricular septal defect (VSD), atrial septal defect (ASD), and trivial patent ductus arteriosus (PDA). While expanding upon the implementation of chest X-ray imaging, serial transthoracic echocardiogram (TTE) imaging, and the balloon atrial septostomy (BAS) procedure, we also provide insight into the multidisciplinary team-based approach utilized for this patient's case. This case illustrates a rare critical CHD coupled with other, more common congenital anomalies, and suggests that with multidisciplinary management and treatment, it is possible the mortality rates associated with this diagnosis could decline.
PubMed: 38770493
DOI: 10.7759/cureus.58596 -
World Journal For Pediatric &... May 2024Postoperative restenosis of the aortic arch after the Norwood procedure is still an important complication that significantly affects surgical outcomes. The rarity of...
Postoperative restenosis of the aortic arch after the Norwood procedure is still an important complication that significantly affects surgical outcomes. The rarity of the Norwood procedure for atypical aortic morphology means appropriate arch reconstruction methods and postoperative complications are still unknown. This study aimed to assess the rate of arch reintervention and clinical outcomes after the Norwood procedure for atypical aortic arch. This retrospective single-center study was conducted between 2001 and 2022. Sixteen patients were identified, eight with a right aortic arch, five with transposition of the great arteries, one with a right aortic arch and transposition of the great arteries, and two with a large tortuous patent ductus arteriosus connected to the opposite side of the descending aorta. We selected and performed four different surgical techniques depending on each aortic arch morphology. Except for one case, autologous tissue-only arch reconstruction was possible. There was one operative death and four late deaths. Overall, no patients required any surgical or catheter-based reintervention for the aortic arch. On the other hand, left pulmonary artery stenosis due to a narrow subaortic space was found in two patients. The Norwood procedure for atypical aortic arch was performed with good results by choosing the appropriate technique for each morphology. On the other hand, pulmonary artery stenosis is likely to occur especially in the transposition of the great arteries group. Therefore, careful surgical method selection or further improvement of the technique that allows retroaortic space should be considered.
PubMed: 38766734
DOI: 10.1177/21501351241235953 -
BMC Pregnancy and Childbirth May 2024To explore a method for screening and diagnosing neonatal congenital heart disease (CHD) applicable to grassroots level, evaluate the prevalence of CHD, and establish a...
A "twelve-section ultrasonic screening and diagnosis method" and management system for screening and treating neonatal congenital heart disease at the grassroots level in Tang County, Hebei Province, China.
BACKGROUND
To explore a method for screening and diagnosing neonatal congenital heart disease (CHD) applicable to grassroots level, evaluate the prevalence of CHD, and establish a hierarchical management system for CHD screening and treatment at the grassroots level.
METHODS
A total of 24,253 newborns born in Tang County between January 2016 and December 2020 were consecutively enrolled and screened by trained primary physicians via the "twelve-section ultrasonic screening and diagnosis method" (referred to as the "twelve-section method"). Specialized staff from the CHD Screening and Diagnosis Center of Hebei Children's Hospital regularly visited the local area for definite diagnosis of CHD in newborns who screened positive. Newborns with CHD were managed according to the hierarchical management system.
RESULTS
The centre confirmed that, except for 2 newborns with patent ductus arteriosus missed in the diagnosis of ventricular septal defect combined with severe pulmonary hypertension, newborns with other isolated or concomitant simple CHDs were identified at the grassroots level. The sensitivity, specificity and diagnostic coincidence rate of the twelve-section method for screening complex CHD were 92%, 99.6% and 84%, respectively. A total of 301 children with CHD were identified. The overall CHD prevalence was 12.4‰. According to the hierarchical management system, 113 patients with simple CHD recovered spontaneously during local follow-up, 48 patients continued local follow-up, 106 patients were referred to the centre for surgery (including 17 patients with severe CHD and 89 patients with progressive CHD), 1 patient died without surgery, and 8 patients were lost to follow-up. Eighteen patients with complex CHD were directly referred to the centre for surgery, 3 patients died without surgery, and 4 patients were lost to follow-up. Most patients who received early intervention achieved satisfactory results. The mortality rate of CHD was approximately 28.86 per 100,000 children.
CONCLUSIONS
The "twelve-section method" is suitable for screening neonatal CHD at the grassroots level. The establishment of a hierarchical management system for CHD screening and treatment is conducive to the scientific management of CHD, which has important clinical and social significance for early detection, early intervention, reduction in mortality and improvement of the prognosis of complex and severe CHDs.
Topics: Humans; Heart Defects, Congenital; Infant, Newborn; China; Neonatal Screening; Female; Male; Prevalence; Sensitivity and Specificity
PubMed: 38750445
DOI: 10.1186/s12884-024-06569-x