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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 -
Journal of Medical Genetics Jul 2023Genetic deletions at Xp22.31 are associated with the skin condition X linked ichthyosis (XLI), and with a substantially increased risk of atrial fibrillation/flutter...
BACKGROUND
Genetic deletions at Xp22.31 are associated with the skin condition X linked ichthyosis (XLI), and with a substantially increased risk of atrial fibrillation/flutter (AF), in males. AF is associated with elevated thrombosis, heart failure, stroke and dementia risk.
METHODS
Through: (a) examining deletion carriers with a diagnosis of AF in UK Biobank, (b) undertaking an online survey regarding abnormal heart rhythms (AHRs) in men/boys with XLI and female carriers of XLI-associated deletions and (c) screening for association between common genetic variants within Xp22.31 and idiopathic AF-related conditions in UK Biobank, we have investigated how AHRs manifest in deletion carriers, and have identified associated risk factors/comorbidities and candidate gene(s). Finally, we examined attitudes towards heart screening in deletion carriers.
RESULTS
We show that AHRs may affect up to 35% of deletion carriers (compared with <20% of age-matched non-carriers), show no consistent pattern of onset but may be precipitated by stress, and typically resolve quickly and respond well to intervention. Gastrointestinal (GI) conditions and asthma/anaemia were the most strongly associated comorbidities in male and female deletion carriers with AHR, respectively. Genetic analysis indicated significant enrichment of common AF risk variants around (7 065 298-7 272 682 bp in GRCh37/hg19 genome build) in males, and of common GI disorder and asthma/anaemia risk variants around (7 866 804-7 895 780 bp) in males and females, respectively. Deletion carriers were overwhelmingly in favour of cardiac screening implementation.
CONCLUSION
Our data suggest AHRs are frequently associated with Xp22.31 deletion, and highlight subgroups of deletion carriers that may be prioritised for screening. Examining cardiac function further in deletion carriers, and in model systems lacking steroid sulfatase, may clarify AF pathophysiology.
Topics: Humans; Male; Female; Ichthyosis, X-Linked; Heterozygote; Surveys and Questionnaires; Heart Defects, Congenital; Heart
PubMed: 36379544
DOI: 10.1136/jmg-2022-108862 -
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 -
Genes Oct 2023Axenfeld-Rieger anomaly (ARA) is a specific ocular disorder that is frequently associated with other systemic abnormalities. and variants explain the majority of...
Axenfeld-Rieger anomaly (ARA) is a specific ocular disorder that is frequently associated with other systemic abnormalities. and variants explain the majority of individuals with Axenfeld-Rieger syndrome (ARS) but leave ~30% unsolved. Here, we present pathogenic/likely pathogenic variants in nine families with ARA/ARS or similar phenotypes affecting five different genes/regions. and explained three families each. was recently linked with syndromic cognitive impairment that includes hearing loss, dental defects, ventriculomegaly, Dandy-Walker malformation, skeletal anomalies (hip dysplasia), and other features showing a significant overlap with -ARS. Anterior segment anomalies are not currently associated with , yet our cases demonstrate ARA, congenital glaucoma, corneal neovascularization, and cataracts. The identification of variants, linked with Alagille syndrome, in three separate families with a clinical diagnosis of ARA/ARS highlights the overlapping features and high variability of these two phenotypes. Finally, intragenic variants in , , and an X chromosome deletion encompassing and (linked with ocular and dental anomalies, correspondingly) were identified in three additional cases with ARS. Accurate diagnosis has important implications for clinical management. We suggest that broad testing such as exome sequencing be applied as a second-tier test for individuals with ARS with normal results for sequencing and copy number analysis, with attention to the described genes/regions.
Topics: Humans; Transcription Factors; Homeodomain Proteins; Anterior Eye Segment; Eye Abnormalities; Ubiquitin Thiolesterase
PubMed: 37895297
DOI: 10.3390/genes14101948