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Circulation. Heart Failure Jul 2023Patients with pulmonary hypertension associated with congenital heart disease make up an increasing proportion of the total pulmonary hypertension population who bring... (Review)
Review
Patients with pulmonary hypertension associated with congenital heart disease make up an increasing proportion of the total pulmonary hypertension population who bring with them added complexity because of underlying anatomical and hemodynamic abnormalities. Currently, no consensus recommendations are available on how to best manage this group of patients for either the primary cardiologist or pulmonary hypertension subspecialist, including timing of referral. The purposes of this document are (1) to describe the various pulmonary hypertension groups and subgroups associated with congenital heart disease, (2) to describe imaging modalities used in patient evaluation, (3) to elucidate medical and surgical management considerations, (4) to highlight disparities within this population, and (5) to identify gaps and future research needs of patients with pulmonary hypertension associated with congenital heart disease.
Topics: United States; Humans; Hypertension, Pulmonary; American Heart Association; Heart Failure; Heart Defects, Congenital; Hemodynamics
PubMed: 37357777
DOI: 10.1161/HHF.0000000000000080 -
The Journal of Clinical Investigation Apr 2024Capillary malformation (CM), or port wine birthmark, is a cutaneous congenital vascular anomaly that occurs in 0.1%-2% of newborns. Patients with a CM localized on the... (Review)
Review
Capillary malformation (CM), or port wine birthmark, is a cutaneous congenital vascular anomaly that occurs in 0.1%-2% of newborns. Patients with a CM localized on the forehead have an increased risk of developing a neurocutaneous disorder called encephalotrigeminal angiomatosis or Sturge-Weber syndrome (SWS), with complications including seizure, developmental delay, glaucoma, and vision loss. In 2013, a groundbreaking study revealed causative activating somatic mutations in the gene (GNAQ) encoding guanine nucleotide-binding protein Q subunit α (Gαq) in CM and SWS patient tissues. In this Review, we discuss the disease phenotype, the causative GNAQ mutations, and their cellular origin. We also present the endothelial Gαq-related signaling pathways, the current animal models to study CM and its complications, and future options for therapeutic treatment. Further work remains to fully elucidate the cellular and molecular mechanisms underlying the formation and maintenance of the abnormal vessels.
Topics: Infant, Newborn; Animals; Humans; Glaucoma; Models, Animal; Mutation; Capillaries; Vascular Malformations
PubMed: 38618955
DOI: 10.1172/JCI172842 -
European Journal of Paediatric Dentistry Sep 2023Otodental syndrome is a rare autosomal dominant condition characterised by a dental phenotype known as globodontia often associated with high-frequency hearing loss....
Otodental syndrome is a rare autosomal dominant condition characterised by a dental phenotype known as globodontia often associated with high-frequency hearing loss. Globodontia occurs both in the decidous and permanent dentition and affects canine and molar teeth.
Topics: Humans; Chromosome Disorders; Hearing Loss, Sensorineural; Tooth Abnormalities; Arthrogryposis
PubMed: 37668456
DOI: 10.23804/ejpd.2023.24.03.03 -
The Canadian Veterinary Journal = La... Aug 2023. A 3-year-old female dog was referred for exploration of a murmur concomitant with lethargy. An echocardiogram reveals an inversion of the position of the cardiac...
. A 3-year-old female dog was referred for exploration of a murmur concomitant with lethargy. An echocardiogram reveals an inversion of the position of the cardiac chambers and the presence of an interventricular communication. A computed tomography examination of the thorax and abdomen highlights the known cardiac abnormalities as well as the association of a complete . The clinical examination also reveals ocular malformations (deviation of the eyeballs and asymmetry of the fundus). This article highlights the variety of abnormalities that can be associated with the complete inversion of the organs and demonstrates that there may be variants to the more classic picture usually encountered in humans (respiratory manifestations related to Kartagener syndrome).(Translated by D Serge Messier).
Topics: Humans; Female; Dogs; Animals; Situs Inversus; Kartagener Syndrome; Heart Septal Defects, Ventricular; Tomography, X-Ray Computed; Dog Diseases
PubMed: 37529390
DOI: No ID Found -
European Review For Medical and... Jan 2024Holt-Oram syndrome (HOS) is a rare genetic illness, which concerns disturbances in the appearance of the upper limbs, congenital heart malformations, and cardiac...
BACKGROUND
Holt-Oram syndrome (HOS) is a rare genetic illness, which concerns disturbances in the appearance of the upper limbs, congenital heart malformations, and cardiac conduction diseases. HOS usually requires the implantation of a pacemaker, because of cardiac conduction disturbances.
CASE REPORT
We present the case of a patient with HOS qualified for pacemaker implantation due to overt bradycardia. To prevent the development of heart failure in the future, the His-bundle pacing technique was used. The implantation was successful. In the control, after one year, the man remains in good condition. The pacing was over 90%, and the left ventricular ejection fraction (LVEF) was stable (60%).
CONCLUSIONS
So far, there are no reports on which methods of stimulation are required when it comes to patients with HOS. His-bundle pacing technique is a new type of physiological pacing, which can avoid heart failure.
Topics: Humans; Stroke Volume; Ventricular Function, Left; Heart Septal Defects, Atrial; Cardiac Conduction System Disease; Heart Failure; Abnormalities, Multiple; Heart Defects, Congenital; Lower Extremity Deformities, Congenital; Upper Extremity Deformities, Congenital
PubMed: 38235884
DOI: 10.26355/eurrev_202401_34921 -
Human Molecular Genetics Jul 2023FOXJ1 is expressed in ciliated cells of the airways, testis, oviduct, central nervous system and the embryonic left-right organizer. Ablation or targeted mutation of...
FOXJ1 is expressed in ciliated cells of the airways, testis, oviduct, central nervous system and the embryonic left-right organizer. Ablation or targeted mutation of Foxj1 in mice, zebrafish and frogs results in loss of ciliary motility and/or reduced length and number of motile cilia, affecting the establishment of the left-right axis. In humans, heterozygous pathogenic variants in FOXJ1 cause ciliopathy leading to situs inversus, obstructive hydrocephalus and chronic airway disease. Here, we report a novel truncating FOXJ1 variant (c.784_799dup; p.Glu267Glyfs*12) identified by clinical exome sequencing from a patient with isolated congenital heart defects (CHD) which included atrial and ventricular septal defects, double outlet right ventricle (DORV) and transposition of the great arteries. Functional experiments show that FOXJ1 c.784_799dup; p.Glu267Glyfs*12, unlike FOXJ1, fails to induce ectopic cilia in frog epidermis in vivo or to activate the ADGB promoter, a downstream target of FOXJ1 in cilia, in transactivation assays in vitro. Variant analysis of patients with heterotaxy or heterotaxy-related CHD indicates that pathogenic variants in FOXJ1 are an infrequent cause of heterotaxy. Finally, we characterize embryonic-stage CHD in Foxj1 loss-of-function mice, demonstrating randomized heart looping. Abnormal heart looping includes reversed looping (dextrocardia), ventral looping and no looping/single ventricle hearts. Complex CHDs revealed by histological analysis include atrioventricular septal defects, DORV, single ventricle defects as well as abnormal position of the great arteries. These results indicate that pathogenic variants in FOXJ1 can cause isolated CHD.
Topics: Humans; Male; Forkhead Transcription Factors; Heart Atria; Heart Defects, Congenital; Heart Septal Defects; Heterotaxy Syndrome; Transposition of Great Vessels
PubMed: 37158461
DOI: 10.1093/hmg/ddad065 -
African Journal of Paediatric Surgery :... Jan 2024Male congenital urethrocutaneous fistula is an extremely rare anomaly that is commonly associated with chordee or anorectal malformations. It is characterised by an...
Male congenital urethrocutaneous fistula is an extremely rare anomaly that is commonly associated with chordee or anorectal malformations. It is characterised by an abnormal urethral opening on the ventral aspect of the penis with well-formed distal urethra and meatus at the tip of the glans. The treatment is individualised according to the site of the fistula, associated anomalies and condition of the distal urethra. The principles of hypospadias surgery should be strictly followed.
Topics: Male; Humans; Hypospadias; Anorectal Malformations; Urethra
PubMed: 38259026
DOI: 10.4103/ajps.ajps_97_22 -
Genes Nov 2023Cardiofaciocutaneous (CFC) syndrome is one of the rarest RASopathies characterized by multiple congenital ectodermal, cardiac and craniofacial abnormalities with a mild... (Review)
Review
Cardiofaciocutaneous (CFC) syndrome is one of the rarest RASopathies characterized by multiple congenital ectodermal, cardiac and craniofacial abnormalities with a mild to severe ocular, gastrointestinal and neurological involvement. It is an autosomal dominant syndrome, with complete penetrance, caused by heterozygous pathogenic variants in the genes , , , or, rarely, , all part of the RAS-MAPK pathway. This pathway is a signal transduction cascade that plays a crucial role in normal cellular processes such as cell growth, proliferation, differentiation, survival, metabolism and migration. CFC syndrome overlaps with Noonan syndrome, Costello syndrome, neurofibromatosis type 1 and Legius syndrome, therefore making the diagnosis challenging. Neurological involvement in CFC is more severe than in other RASopathies. Phenotypic variability in CFC patients is related to the specific gene affected, without a recognized genotype-phenotype correlation for distinct pathogenic variants. Currently, there is no specific treatment for CFC syndrome. Encouraging zebrafish model system studies suggested that, in the future, MEK inhibitors could be a suitable treatment of progressive phenotypes of CFC in children. A multidisciplinary care is necessary for appropriate medical management.
Topics: Child; Animals; Humans; Prognosis; Zebrafish; Ectodermal Dysplasia; Heart Defects, Congenital
PubMed: 38136934
DOI: 10.3390/genes14122111 -
European Journal of Human Genetics :... Aug 2023High-throughput sequencing has become a standard first-tier approach for both diagnostics and research-based genetic testing. Consequently, this hypothesis-free... (Review)
Review
High-throughput sequencing has become a standard first-tier approach for both diagnostics and research-based genetic testing. Consequently, this hypothesis-free testing manner has revealed the true breadth of clinical features for many established genetic disorders, including Meier-Gorlin syndrome (MGORS). Previously known as ear-patella short stature syndrome, MGORS is characterized by growth delay, microtia, and patella hypo/aplasia, as well as genital abnormalities, and breast agenesis in females. Following the initial identification of genetic causes in 2011, a total of 13 genes have been identified to date associated with MGORS. In this review, we summarise the genetic and clinical findings of each gene associated with MGORS and highlight molecular insights that have been made through studying patient variants. We note interesting observations arising across this group of genes as the number of patients has increased, such as the unusually high number of synonymous variants affecting splicing in CDC45 and a subgroup of genes that also cause craniosynostosis. We focus on the complicated molecular genetics for DONSON, where we examine potential genotype-phenotype patterns using the first 3D structural model of DONSON. The canonical role of all proteins associated with MGORS are involved in different stages of DNA replication and in addition to summarising how patient variants impact on this process, we discuss the potential contribution of non-canonical roles of these proteins to the pathophysiology of MGORS.
Topics: Female; Humans; Congenital Microtia; Patella; Growth Disorders; Micrognathism
PubMed: 37059840
DOI: 10.1038/s41431-023-01359-z -
Taiwanese Journal of Obstetrics &... Jan 2024Fetal megacystis has been reported to be associated with chromosomal abnormalities, megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS), obstructive... (Review)
Review
Fetal megacystis has been reported to be associated with chromosomal abnormalities, megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS), obstructive uropathy, prune belly syndrome, cloacal anomalies, limb-body wall complex, amniotic band syndrome, anorectal malformations, VACTERL association (vertebral anomalies, anal atresia, cardiac malformations, tracheo-esophageal fistula, renal anomalies and limb abnormalities) and fetal overgrowth syndrome such as Bechwith-Wiedemann syndrome and Sotos syndrome. This review provides an overview of chromosomal abnormalities associated with fetal megacystis which is useful for genetic counseling and fetal therapy at prenatal diagnosis of fetal megacystis.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Diabetes, Gestational; Fetal Macrosomia; Abnormalities, Multiple; Chromosome Aberrations; Urinary Bladder; Duodenum; Fetal Diseases
PubMed: 38216262
DOI: 10.1016/j.tjog.2023.11.006