Atypical superotemporal iris and retinal coloboma

Incidence of congenital heart disease in Palestinian children born in the Gaza Strip, occupied Palestinian territory: a cross-sectional study

Absent pulmonary valve syndrome (APVS) is a rare anomaly characterized by the absence of the pulmonary valve. The absence of the pulmonary valve, along with the hypoplasia of the pulmonary annulus, leads to aneurysmal dilatation of the pulmonary artery and its branches. Other consequences include pulmonary stenosis and pulmonary insufficiency (1). The 3-day-old baby presented with cyanosis and tachypnea. He had to and fro murmurs at the upper left sternal region, as well as hepatomegaly. The electrocardiogram showed right ventricular hypertrophy. The posterior-anterior chest X-ray showed opaque left hemithorax with cardiac displacement (Figure 1). Upon echocardiographic examination, the following findings were noted: the right cardiac chambers were dilated and left ventricular hypoplasia was present (Video 1. See corresponding video/movie images at www.balkanmedicaljournal.org). A large subaortic ventricular septal defect and a main pulmonary artery aneurysm were seen (Video 2. See corresponding video/movie images at www.balkanmedicaljournal.org). Hypoplastic pulmonary annulus and absent pulmonary valve leaflets were present (Figure 2). Moderate pulmonary stenosis (peak systolic gradient was 45 mmHg) and mild pulmonary regurgitation were present (Video 3. See corresponding video/movie images at www.balkanmedical-journal.org). The aortic arc was left sided and no patent ductus arteriosus was seen. In addition to the echocardiographic findings, atresia of the left pulmonary artery was observed with computed tomography (Figures 3, ​,4).4). The patient died due to respiratory failure on fourth day after birth. FIG. 1 Posterior-anterior chest X-ray showed opaque left hemithorax with cardiac displacement FIG. 2 Hypoplastic pulmonary annulus and absent pulmonary valve leaflets FIG. 3 CT 3D reconstruction of aneurysmal pulmonary arteries FIG. 4 Left pulmonary artery atresia Absent pulmonary valve syndrome is a rare anomaly, which is characterized by aneurysmal dilatation of the pulmonary artery, depending on atresia or dysplasia of the pulmonary valve leaflets. The disease is usually associated with tetralogy of Fallot. Due to the absence of pulmonary valve leaflets, pulmonary regurgitation and mild pulmonary stenosis were seen (2). Respiratory distress signs could be seen to varying degrees due to compression of the airway with the pulmonary artery. In the severe forms, due to complete obstruction of the trachea or bronchi, rapid progress can be seen in the neonatal period. More severe forms of the disease may result in death during the newborn period due to the pressure effect exerted by the pulmonary artery on the tracheobronchial structures. The patient presented herein had an absence of the pulmonary valve, together with the non-restrictive ventricular septal defect. Also, mild pulmonary valve stenosis and insufficiency, widened pulmonary artery, and atresia of the left pulmonary artery were seen. Although catheterization could not be performed during the early stage, as the patient had severe respiratory dysfunction, computed tomography confirmed the presence of a widened pulmonary artery and atresia of the left pulmonary artery. Also, arterial branches from the abdominal or thoracic aorta supplying the left lung could not be detected with computed tomography. The combination of APVS with atresia of the left pulmonary artery is extremely rare (3). Early diagnosis and supportive treatment in the newborn period are important for the survival of these severely affected infants.

The prevalence of adult congenital heart disease (ACHD) has risen markedly over the past 2 decades, with the number of adults now rivaling the number of children with severe defects.1 This is, perhaps, not surprising given that current care allows nearly 90% of infants born with heart defects to thrive into their adult years.1,2 This remarkable triumph is tempered, however, by the realization that early interventions were reparative and not curative. Numerous complications may surface years after uneventful childhood courses, justifying vigilant clinical follow-up throughout adulthood. The 12-lead ECG remains an invaluable cornerstone in the clinical appraisal of adults with congenital heart disease that, in certain circumstances, provides diagnostic and/or prognostic information. The present review imparts a clinical perspective to ECG interpretation in ACHD, emphasizing practical and pathogenomonic findings in the more frequently encountered congenital defects in adults. Anatomic features of the conduction system relevant to ECG findings in ACHD are summarized, including variations in the location of the sinus node, atrioventricular (AV) node, and His-Purkinje system. Thereafter, pertinent ECG features are highlighted for common subtypes of ACHD (Table). Examples are provided throughout for illustration. View this table: Table. Typical ECG Features in Common Forms of ACHD ### Sinus Node In the morphologically normal heart, a crescent-shaped sinus node is characteristically located epicardially along the lateral aspect of the superior cavoatrial junction. It generates a P-wave axis typically between 15° and 75°. Most patients with ACHD have normally positioned atrial chambers, called atrial situs solitus, with normal sinus node location. The position of the sinus node may, however, vary with the atrial chambers and their appendages. #### Juxtaposition of the Atrial Appendages In juxtaposition of the atrial appendages, both appendages are on the same side of the arterial pedicle rather than each being ipsilateral to its respective atrium. Left juxtaposition, with left-sided atrial appendages, frequently accompanies tricuspid atresia and has …

The dominant features of congenital heart lesions with left-to-right shunts observed by conventional roentgen examination are increase of pulmonary vascularity and enlargement of the heart. Of particular importance is the differential diagnosis of atrial and ventricular septal defects. Increased size of the left atrium indicates a shunt distal to the atrioventricular valve, while no enlargement of the left atrium is found in atrial septal defects (2). In ventricular septal defects clinical signs of enlargement of the left ventricle are usually present. In cases of secundum atrial septal defect the left ventricle is presumably of normal size. Assessment of the size and configuration of the left ventricle on the basis of conventional roentgenography is generally considered difficult since available criteria are hard to apply in practice. In the determination of left ventricular dilatation, however, the topographical relationship of the inferior vena cava to the posterior surface of the heart in the lateral projection of the chest is a valuable diagnostic aid. It occurred to us that since left ventricular dilatation does not occur in atrial secundum septal defects but is the rule in ventricular septal defects with significant shunts, such altered relationship of the left ventricle to the inferior vena cava might be useful in differentiating these lesions. This report concerns our experience with the utilization of this sign. Methods To test the validity of this concept, all cases of ventricular and atrial secundum septal defects at the Children's Clinic of the Karolinska Hospital were reviewed. Each case was proved by cardiac catheterization and angiography. The series included some adults who were brought to the Children's Clinic for angiocardiography. All patients under four years of age were eliminated from the group because of the recognized difficulties in obtaining chest roentgenograms in full inspiration at this age. Also excluded from the series were patients in whom the degree of inspiration was so shallow as to prevent visualization of the inferior vena cava in the lateral projection. Of the patients with ventricular septal defect, only significant shunts were considered, as small shunts characteristically produce no significant alteration in cardiac contour and therefore do not constitute a problem in differential diagnosis from the atrial septal defect. It was felt that a significant shunt was present in the included cases of ventricular septal defect if cardiac enlargement and definite increase in prominence of the pulmonary vasculature were evident. Since patients with atrial septal defects typically have large shunts and radiologically detectable alterations in heart size and pulmonary vascularity, there was no necessity to eliminate any of these on the basis of size of the shunt.

To use whole exome sequencing (WES) of a family trio to identify a genetic cause for polyvalvular syndrome. A male child was born with mild pulmonary valve stenosis and mild aortic root dilatation, and an atrial septal defect, ventricular septal defect, and patent ductus arteriosus that were closed surgically. Subsequently, the phenotype of polyvalvular syndrome with involvement of both semilunar and both atrioventricular valves emerged. His family history was negative for congenital heart disease. Because of hypotonia, myopia, soft pale skin, joint hypermobility, and mild facial dysmorphism, either Noonan syndrome- or William syndrome-spectrum disorders were suspected clinically. However, chromosomal analysis was normal and commercially available Noonan syndrome and William syndrome genetic tests were negative. Whole exome sequencing of the patient and both parents was performed. Variants were analyzed by sporadic and autosomal recessive inheritance models. A sporadic mutation, annotated as c.1491 T > A, in TAB2, resulting in a nonsense mutation, p.Y497X, in the TAB2-encoded TGF-beta activated kinase 1 (TAK1) was identified as the most likely disease-susceptibility gene. This mutation results in elimination of the terminal 197 amino acids, including the C-terminal binding motif critical for interactions with TRAF6 and TAK1. The combination of WES, genomic triangulation, and systems biology has uncovered perturbations in TGF-beta activated kinase 1 signaling as a novel pathogenic substrate for polyvalvular syndrome.

Genome maps, like geographical maps, need to be interpreted carefully. Although maps are essential to exploration and navigation they cannot be completely accurate. Humans have been mapping the world for several millennia, but genomes have been mapped and explored for just a single century with the greatest advancements in making a sequence reference map of the human genome possible in the past 30 years. After the deoxyribonucleic acid (DNA) sequence of the human genome was completed in 2003, the reference sequence underwent several improvements and today provides the underlying comparative resource for a multitude genetic assays and biochemical measurements. However, the ability to simplify genetic analysis through a single comprehensive map remains an elusive goal. Key Concepts: Maps are incomplete and contain errors. DNA sequence data are interpreted through biochemical experiments or comparisons to other DNA sequences. A reference genome sequence is a map that provides the essential coordinate system for annotating the functional regions of the genome and comparing differences between individuals' genomes. The reference genome sequence is always product of understanding at a set point in time and continues to evolve. DNA sequences evolve through duplication and mutation and, as a result, contain many repeated sequences of different sizes, which complicates data analysis. DNA sequence variation happens on large and small scales with respect to the lengths of the DNA differences to include single base changes, insertions, deletions, duplications and rearrangements. DNA sequences within the human population undergo continual change and vary highly between individuals. The current reference genome sequence is a collection of sequences, an assembly, that include sequences assembled into chromosomes, sequences that are part of structurally complex regions that cannot be assembled, patches (fixes) that cannot be included in the primary sequence, and high variability sequences that are organised into alternate loci. Genetic analysis is error prone and the data require validation because the methods for collecting DNA sequences create artifacts and the reference sequence used for comparative analyses is incomplete.

Deoxyribonucleic acid (DNA) sequence analysis of the control region of the mitochondrial DNA (mtDNA) genome was used to identify human skeletal remains returned to the United States government by the Vietnamese government in 1984. The postmortem interval was thought to be 24 years at the time of testing, and the remains presumed to be an American service member. DNA typing methods using nuclear genomic DNA, HLA-DQ alpha and the variable number of tandem repeat (VNTR) locus D1S80, were unsuccessful using the polymerase chain reaction (PCR). Amplification of a portion of the mtDNA control region was performed, and the resulting PCR product subjected to DNA sequence analysis. The DNA sequence generated from the skeletal remains was identical to the maternal reference sequence, as well as the sequence generated from two siblings (sisters). The sequence was unique when compared to more than 650 DNA sequences found both in the literature and provided by personal communications. The individual sequence polymorphisms were present in only 23 of the more than 1300 nucleotide positions analyzed. These results support the observation that in cases where conventional DNA typing is unavailable, mtDNA sequencing can be used for human remains identification.

The aim of this study was to assess the frequency of various forms of congenital heart disease (CHD) among affected children in the Southwestern region of Saudi Arabia. During the study period (July 1994 to June 1996), 608 children were referred to Asir Central Hospital as having CHD. All the children were evaluated by a pediatric cardiologist and had electrocardiogram and echocardiogram. Of the 608 patients, only 335, comprising 162 males and 173 females, had CHD. The male to female ratio was 0.9:1. The frequency of various forms of CHD was as follows: ventricular septal defect (VSD) 32.5%; patent ductus arteriosus 15.8%; atrial septal defect 10.4%; pulmonary stenosis 10.1%; atrioventricular septal defect and mitral valve prolapse, 3.6% each; aortic coarctation/interruption 3.3%; obstructive aortic valve lesions 2.7%; tetralogy of Fallot 4.5%; common ventricle 2.7%; pulmonary atresia (PA) with VSD 1.8%; D-transposition of the great arteries 1.5%; Ebstein anomaly 1.5%; and isolated PA 1.2%. Other lesions were extremely rare. The distribution in this study is similar to that reported in previous studies from other parts of the world, except for the lower incidence of obstructive aortic valve lesions.

The human nuclear genome is organised into a highly complex arrangement of two sets of 23 chromosomes comprised of various types of deoxyribonucleic acid (DNA) sequences. With less than 2% of the human genome consisting of protein‐encoding DNA sequence, the remainder of the 3 × 10 9 bp of the haploid genome consists of a multifaceted assortment of DNA sequence classifications. At the broadest level, the genome can be divided into single‐copy protein‐encoding genes, repetitive sequences and spacer DNA. Notably, the categories of repetitive sequences are profoundly intricate and may be further classified into functional or functionally related groups such as gene families and superfamilies, or groups with no known function such as satellite DNA and transposable elements. Their genomic organisation may be dispersed, within localised regions, and/or tandemly repeated. The generation of repetitive sequences results from a variety of mechanisms continually promoting a genome that is highly dynamic. Key Concepts The human genome is highly complex and dynamic. Only 2–4% of the three billion base pairs of the human genome consists of protein‐encoding genes, of which only a portion of that is translated into amino acids with some of the sequence being involved in regulation of gene expression. The human genome consists of single or low‐copy genes, moderately repetitive sequences and highly repetitive sequences initially determined utilising reassociation kinetics, with all three categories of DNA found throughout the genome. G‐band staining of chromosomes yield karyograms that define characteristic properties and organisation of the genome. Repetitive DNA sequences comprise a large proportion of the genome and may be dispersed and/or in tandem arrays. The repetitive sequences in the genome may be functional or serve no known function. Functional repetitive sequences may encode protein or RNA molecules. A large fraction of DNA sequences in the human genome have been generated via mechanisms such as unequal crossing over yielding either functional, or nonfunctional pseudogene, copies typically adjacent to each other, as well as by reverse transcription which yields retrocopies dispersed throughout the genome. Functional tandem repeats of DNA sequences are localised in certain chromosomal regions, for example the rRNA genes within nucleolar organiser regions (NORs), providing numerous copies of genes typically having general functions (e.g. protein synthesis). Telomeres are the sequences at the ends of the chromosomes that consist of tandemly repeated sequences associated with stability and maintenance of chromosome size after cell division.

To determine the long-term natural history of patients with mild pulmonary valve stenosis. Throughout a 24-year evolutive period (1980 to 2004), 83 patients with pulmonary valve stenosis were evaluated, with 29 of them presenting a mild form of the defect. Of these 29, 13 patients had a long-term follow up. The mean age at the first and last follow-up visits was 34 months (1 month to 15 years) and 10.5 years (3 to 24 years), respectively. In addition to evolutive elements, those regarding clinical, electrocardiographic and echocardiographic aspects were also assessed. All patients remained asymptomatic throughout the study. Regarding the pulmonary valve pressure gradient, 5 (38.4%) presented a decrease, 3 (23%) remained unchanged, 4 (30.7%) presented elimination and 1 (7.6%) presented accentuation to a moderate degree of involvement. The mean initial and final gradient was 24.2 mmHg (15-30) and 13.6 mmHg (0-54), respectively. The initial gradients of the 4 patients who achieved spontaneous cure were 30, 19, 30 and 20 mmHg. The systolic murmur and right ventricular overload had a direct correlation to the gradient pressure degree, subdivided at each 10 mmHg. The spontaneous cure of the mild pulmonary valve stenosis is possible to achieve, similarly to other acyanogenic anomalies.

Deoxyribonucleic acid (DNA) sequences are difficult to analyze similarity due to their length and complexity. The challenge lies in being able to use digital signal processing (DSP) to solve highly relevant problems in DNA sequences. Here, we transfer a one-dimensional (1D) DNA sequence into a two-dimensional (2D) pattern by using the Peano scan algorithm. Four complex values are assigned to the characters "A", "C", "T", and "G", respectively. Then, Fourier transform is employed to obtain far-field amplitude distribution of the 2D pattern. Hereto, a 1D DNA sequence becomes a 2D image pattern. Features are extracted from the 2D image pattern with the Principle Component Analysis (PCA) method. Therefore, the DNA sequence database can be established. Unfortunately, comparing features may take a long time when the database is large since multi-dimensional features are often available. This problem is solved by building indexing structure like a filter to filter-out non-relevant items and select a subset of candidate DNA sequences. Clustering algorithms can organize the multi-dimensional feature data into the indexing structure for effective retrieval. Accordingly, the query sequence can be only compared against candidate ones rather than all sequences in database. In fact, our algorithm provides a pre-processing method to accelerate the DNA sequence search process. Finally, experimental results further demonstrate the efficiency of our proposed algorithm for DNA sequences similarity retrieval.

Background: Atrial septal defects (ASD) and ventricular septal defects (VSD) are among the most common forms of congenital heart disease (CHD). Early detection and intervention for these defects are crucial to prevent complications. Given advancements in AI technology, the development of AI-enabled ECG models for detecting these defects is of significant interest. Aims: This study aimed to create AI models using pediatric ECG data for the detection of ASD, VSD, and a combined model detecting either ASD or VSD. Methods: We analyzed a dataset of 7,795 pediatric patients from Mayo Clinic who had undergone echocardiography between 2002 and 2022, with corresponding 10-second, 12-lead surface ECGs taken within 14 days of echocardiography. This dataset included 259 patients with ASDs and 139 patients with VSDs (single or multiple). The control group was comprised of 7,397 patients without significant or complex CHD. For cases and controls, we included patients with all forms of electrocardiographic abnormalities and those with valvular lesions who had less than moderate stenosis or regurgitation. The dataset was divided into training, validation, and testing subsets to develop convolutional neural network (CNN) models for ASD, VSD, and either ASD or VSD detection. Results: Our ASD and VSD detection models achieved test AUCs of 0.82 (95% CI 0.76, 0.88) and 0.80 (95% CI 0.70, 0.90), respectively. Meanwhile, a combined model that detected either ASD or VSD demonstrated a test AUC of 0.81 (95% CI, 0.76, 0.86), sensitivity of 0.73, specificity of 0.76, PPV of 0.14, and NPV of 0.98 (Figure 1). Conclusions: AI-enabled ECG models demonstrate promising performance in detecting ASD and VSD in pediatric patients. A combined model that detects either ASD or VSD also shows robust results. Future research should focus on multi-center validation of these models, refining their diagnostic capacities, and investigating their potential for early intervention in CHDs.

Modified Nikaidoh Procedure With Double-Root Translocation in a 1-Year-Old Boy

We report on a prenatally diagnosed four-month-old boy with DiGeorge-like phenotype and a deletion of chromosome 10pter --> 14. Fluorescence in situ hybridization (FISH) experiments using phage artificial chromosome (PAC) and yeast artificial chromosome (YAC) clones indicated that the chromosomal breakpoint was located at the proximal boundary of the DiGeorge syndrome 2 (DGS2) critical region. The patient demonstrated a high forehead, high arched eyebrows, short palpebral fissures, sparse eyelashes, prominent nose with bulbous tip, small mouth, receding chin, round ears with deficient helices, cardiac defects atrial septal defect (ASD), ventricular septal defect (VSD), mild brachytelephalangy, mild syndactyly, hypoplastic left kidney, undescended testes, muscular hypertonia, dorsally flexed big toes, and developmental delay. The phenotype corresponded well with the clinical signs of 10p deletion of this region that were described previously. The facial features appeared different from the typical face with the 22q11 deletion.

The association of congenital heart defects with trisomy 21 was reported over 50 years ago and heart defects remain one of the most common and lethal abnormalities present postnatally in individuals affected by Down syndrome1–4. The purpose of this Editorial is to review the use of second-trimester fetal echocardiography as an adjunct to the genetic sonogram from a clinical perspective, based on my experience over the past 20 years5–13. The following topics are discussed as they relate to trisomy 21: (1) the incorporation of ultrasound evaluation of the fetal heart as part of the genetic sonogram and comparison of it with other screening modalities from a historical perspective; (2) the postnatal incidence of congenital heart defects; (3) the prenatal incidence of structural and functional heart abnormalities; (4) the relative risk for various cardiac findings; and (5) the suggested use of fetal echocardiography as part of the genetic sonogram given current screening technologies.