Mental health outcomes for survivors of critical congenital heart disease (CHD) remain under-investigated. We sought to examine psychiatric disorders and psychosocial functioning in adolescents with ...single ventricle CHD and to explore whether patient-related risk factors predict dysfunction.
This cohort study recruited 156 adolescents with single ventricle CHD who underwent the Fontan procedure and 111 healthy referents. Participants underwent comprehensive psychiatric evaluation including a clinician-rated psychiatric interview and parent- and self-report ratings of anxiety, disruptive behavior, including attention-deficit/hyperactivity disorder (ADHD), and depressive symptoms. Risk factors for dysfunction included IQ, medical characteristics, and concurrent brain abnormalities.
Adolescents with single ventricle CHD had higher rates of lifetime psychiatric diagnosis compared with referents (CHD: 65%, referent: 22%;
< .001). Specifically, they had higher rates of lifetime anxiety disorder and ADHD (
< .001 each). The CHD group scored lower on the primary psychosocial functioning measure, the Children's Global Assessment Scale, than referents (CHD median interquartile range: 62 54-66, referent: 85 73-90;
< .001). The CHD group scored worse on measures of anxiety, disruptive behavior, and depressive symptoms. Genetic comorbidity did not impact most psychiatric outcomes. Risk factors for anxiety disorder, ADHD, and lower psychosocial functioning included lower birth weight, longer duration of deep hypothermic circulatory arrest, lower intellectual functioning, and male gender.
Adolescents with single ventricle CHD display a high risk of psychiatric morbidity, particularly anxiety disorders and ADHD. Early identification of psychiatric symptoms is critical to the management of patients with CHD.
Summary Congenital adrenal hyperplasia is a group of autosomal recessive disorders encompassing enzyme deficiencies in the adrenal steroidogenesis pathway that lead to impaired cortisol biosynthesis. ...Depending on the type and severity of steroid block, patients can have various alterations in glucocorticoid, mineralocorticoid, and sex steroid production that require hormone replacement therapy. Presentations vary from neonatal salt wasting and atypical genitalia, to adult presentation of hirsutism and irregular menses. Screening of neonates with elevated 17-hydroxyprogesterone concentrations for classic (severe) 21-hydroxylase deficiency, the most common type of congenital adrenal hyperplasia, is in place in many countries, however cosyntropin stimulation testing might be needed to confirm the diagnosis or establish non-classic (milder) subtypes. Challenges in the treatment of congenital adrenal hyperplasia include avoidance of glucocorticoid overtreatment and control of sex hormone imbalances. Long-term complications include abnormal growth and development, adverse effects on bone and the cardiovascular system, and infertility. Novel treatments aim to reduce glucocorticoid exposure, improve excess hormone control, and mimic physiological hormone patterns.
The congenital myopathies are a group of early-onset, non-dystrophic neuromuscular conditions with characteristic muscle biopsy findings, variable severity and a stable or slowly progressive course. ...Pronounced weakness in axial and proximal muscle groups is a common feature, and involvement of extraocular, cardiorespiratory and/or distal muscles can implicate specific genetic defects. Central core disease (CCD), multi-minicore disease (MmD), centronuclear myopathy (CNM) and nemaline myopathy were among the first congenital myopathies to be reported, and they still represent the main diagnostic categories. However, these entities seem to belong to a much wider phenotypic spectrum. To date, congenital myopathies have been attributed to mutations in over 20 genes, which encode proteins implicated in skeletal muscle Ca
homeostasis, excitation-contraction coupling, thin-thick filament assembly and interactions, and other mechanisms. RYR1 mutations are the most frequent genetic cause, and CCD and MmD are the most common subgroups. Next-generation sequencing has vastly improved mutation detection and has enabled the identification of novel genetic backgrounds. At present, management of congenital myopathies is largely supportive, although new therapeutic approaches are reaching the clinical trial stage.
The genetics of cognitive epigenetics Kleefstra, Tjitske; Schenck, Annette; Kramer, Jamie M. ...
Neuropharmacology,
05/2014, Letnik:
80
Journal Article
Recenzirano
Cognitive disorders (CDs) are a heterogeneous group of disorders for which the genetic foundations are rapidly being uncovered. The large number of CD-associated gene mutations presents an ...opportunity to identify common mechanisms of disease as well as molecular processes that are of key importance to human cognition. Given the disproportionately high number of epigenetic genes associated with CD, epigenetic regulation of gene transcription is emerging as a process of major importance in cognition. The cognate protein products of these genes often co-operate in shared protein complexes or pathways, which is reflected in similarities between the neurodevelopmental phenotypes corresponding to these mutant genes. Here we provide an overview of the genes associated with CDs, and highlight some of the epigenetic regulatory complexes involving multiple CD genes. Such common gene networks may provide a handle for designing therapeutic interventions applicable to a number of cognitive disorders with variable genetic etiology.
This article is part of the Special Issue entitled ‘Neuroepigenetic Disorders’.
•Mutations in genes encoding modulators of chromatin structure are frequent causes of cognitive disorders.•Proteins encoded these epigenetic genes cluster in functional networks.•Disruption of nodes of these epigenetic gene networks often result is similar phenotypes.
Loss-of-function mutations in Na
1.7 cause congenital insensitivity to pain (CIP); this voltage-gated sodium channel is therefore a key target for analgesic drug development. Utilizing a multi-modal ...approach, we investigated how Na
1.7 mutations lead to human pain insensitivity. Skin biopsy and microneurography revealed an absence of C-fiber nociceptors in CIP patients, reflected in a reduced cortical response to capsaicin on fMRI. Epitope tagging of endogenous Na
1.7 revealed the channel to be localized at the soma membrane, axon, axon terminals, and the nodes of Ranvier of induced pluripotent stem cell (iPSC) nociceptors. CIP patient-derived iPSC nociceptors exhibited an inability to properly respond to depolarizing stimuli, demonstrating that Na
1.7 is a key regulator of excitability. Using this iPSC nociceptor platform, we found that some Na
1.7 blockers undergoing clinical trials lack specificity. CIP, therefore, arises due to a profound loss of functional nociceptors, which is more pronounced than that reported in rodent models, or likely achievable following acute pharmacological blockade. VIDEO ABSTRACT.
Since 1980, the American College of Cardiology (ACC) and American Heart Association (AHA) have translated scientific evidence into clinical practice guidelines (guidelines) with recommendations to ...improve cardiovascular health. These guidelines, which are based on systematic methods to evaluate and classify evidence, provide a cornerstone for quality cardiovascular care. The ACC and AHA sponsor the development and publication of guidelines without commercial support, and members of each organization volunteer their time to the writing and review efforts. Guidelines are official policy of the ACC and AHA.
COVID-19 in Adults With Congenital Heart Disease Broberg, Craig S; Kovacs, Adrienne H; Sadeghi, Soraya ...
Journal of the American College of Cardiology,
04/2021, Letnik:
77, Številka:
13
Journal Article
Recenzirano
Odprti dostop
Adults with congenital heart disease (CHD) have been considered potentially high risk for novel coronavirus disease-19 (COVID-19) mortality or other complications.
This study sought to define the ...impact of COVID-19 in adults with CHD and to identify risk factors associated with adverse outcomes.
Adults (age 18 years or older) with CHD and with confirmed or clinically suspected COVID-19 were included from CHD centers worldwide. Data collection included anatomic diagnosis and subsequent interventions, comorbidities, medications, echocardiographic findings, presenting symptoms, course of illness, and outcomes. Predictors of death or severe infection were determined.
From 58 adult CHD centers, the study included 1,044 infected patients (age: 35.1 ± 13.0 years; range 18 to 86 years; 51% women), 87% of whom had laboratory-confirmed coronavirus infection. The cohort included 118 (11%) patients with single ventricle and/or Fontan physiology, 87 (8%) patients with cyanosis, and 73 (7%) patients with pulmonary hypertension. There were 24 COVID-related deaths (case/fatality: 2.3%; 95% confidence interval: 1.4% to 3.2%). Factors associated with death included male sex, diabetes, cyanosis, pulmonary hypertension, renal insufficiency, and previous hospital admission for heart failure. Worse physiological stage was associated with mortality (p = 0.001), whereas anatomic complexity or defect group were not.
COVID-19 mortality in adults with CHD is commensurate with the general population. The most vulnerable patients are those with worse physiological stage, such as cyanosis and pulmonary hypertension, whereas anatomic complexity does not appear to predict infection severity.
Congenital myasthenic syndromes Finsterer, Josef
Orphanet journal of rare diseases,
02/2019, Letnik:
14, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Congenital myasthenic syndromes (CMSs) are a genotypically and phenotypically heterogeneous group of neuromuscular disorders, which have in common an impaired neuromuscular transmission. Since the ...field of CMSs is steadily expanding, the present review aimed at summarizing and discussing current knowledge and recent advances concerning the etiology, clinical presentation, diagnosis, and treatment of CMSs.
Systematic literature review.
Currently, mutations in 32 genes are made responsible for autosomal dominant or autosomal recessive CMSs. These mutations concern 8 presynaptic, 4 synaptic, 15 post-synaptic, and 5 glycosilation proteins. These proteins function as ion-channels, enzymes, or structural, signalling, sensor, or transporter proteins. The most common causative genes are CHAT, COLQ, RAPSN, CHRNE, DOK7, and GFPT1. Phenotypically, these mutations manifest as abnormal fatigability or permanent or fluctuating weakness of extra-ocular, facial, bulbar, axial, respiratory, or limb muscles, hypotonia, or developmental delay. Cognitive disability, dysmorphism, neuropathy, or epilepsy are rare. Low- or high-frequency repetitive nerve stimulation may show an abnormal increment or decrement, and SF-EMG an increased jitter or blockings. Most CMSs respond favourably to acetylcholine-esterase inhibitors, 3,4-diamino-pyridine, salbutamol, albuterol, ephedrine, fluoxetine, or atracurium.
CMSs are an increasingly recognised group of genetically transmitted defects, which usually respond favorably to drugs enhancing the neuromuscular transmission. CMSs need to be differentiated from neuromuscular disorders due to muscle or nerve dysfunction.
This comprehensive textbook on the echocardiographic assessment of pediatric and congenital heart disease has been updated for a second edition with an emphasis on new technologies. This ...highly-illustrated full-color reference contains over 1200 figures, and offers over 600 video clips on a companion website. * Fully updated, with new chapters on the assessment of the post-Fontan procedure patient and on pregnancy and heart disease * Each lesion chapter includes new section highlighting the key elements of the echocardiogram(s) * Written by experts from the leading centers around the world, with numerous new authors * Revision emphasizes new technologies and quality of images * Comprehensive content contains overview of ultrasound physics, discussion of laboratory set-up, protocol for a standard pediatric echocardiogram and quantitative methods of echocardiographic evaluation, including assessment of diastolic function * Also includes special techniques and topics including 3D echocardiography, intraoperative echocardiography, and fetal echocardiography
Congenital heart disease (CHD), one of the causes of childhood morbidity and mortality, is mainly triggered by a combination of environmental and genetic factors. Several susceptible genes, such as ...NKX2‐5, GATA4 and TBX5, have been reported as closely related to heart and vessel development. CHD subtypes are classified into diverse clinical phenotypes, such as atrial septal defects (ASD), ventricular septal defects (VSD), tetralogy of Fallot (TOF), and Holt–Oram syndrome (HOS). Here, we summarize the associations of the genetic variants in these three genes with CHD subtypes. CHD‐associated variants of NKX2‐5 locate mainly in the tinman domain and the homeodomain. Mutations in the homeodomain are correlated with ASD and atrioventricular (AV) block subtypes. VSD‐associated variants of GATA4 are mainly at its terminal ends. Variants of TBX5 gene are primarily in exons 3, 4, 5 and 7 and highly associated with HOS subtype. Hence, the variant distribution of NKX2‐5, GATA4 and TBX5 are tightly associated with particular CHD subtypes. Further structure‐modelling analysis revealed that these mutated amino acid residuals maintain their DNA‐binding ability and structural stability. Therefore structural features of these genes may be used to predict the high risk of CHD subtypes in infants.
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