Background
Using the National Birth Defects Prevention Network (NBDPN) annual data report, U.S. national prevalence estimates for major birth defects are developed based on birth cohort 2010–2014.
...Methods
Data from 39 U.S. population‐based birth defects surveillance programs (16 active case‐finding, 10 passive case‐finding with case confirmation, and 13 passive without case confirmation) were used to calculate pooled prevalence estimates for major defects by case‐finding approach. Fourteen active case‐finding programs including at least live birth and stillbirth pregnancy outcomes monitoring approximately one million births annually were used to develop national prevalence estimates, adjusted for maternal race/ethnicity (for all conditions examined) and maternal age (trisomies and gastroschisis). These calculations used a similar methodology to the previous estimates to examine changes over time.
Results
The adjusted national birth prevalence estimates per 10,000 live births ranged from 0.62 for interrupted aortic arch to 16.87 for clubfoot, and 19.93 for the 12 critical congenital heart defects combined. While the birth prevalence of most birth defects studied remained relatively stable over 15 years, an increasing prevalence was observed for gastroschisis and Down syndrome. Additionally, the prevalence for atrioventricular septal defect, tetralogy of Fallot, omphalocele, and trisomy 18 increased in this period compared to the previous periods. Active case‐finding programs generally had higher prevalence rates for most defects examined, most notably for anencephaly, anophthalmia/microphthalmia, trisomy 13, and trisomy 18.
Conclusion
National estimates of birth defects prevalence provide data for monitoring trends and understanding the impact of these conditions. Increasing prevalence rates observed for selected conditions warrant further examination.
Congenital heart disease (CHD) patients have an increased prevalence of extracardiac congenital anomalies (CAs) and risk of neurodevelopmental disabilities (NDDs). Exome sequencing of 1213 CHD ...parent-offspring trios identified an excess of protein-damaging de novo mutations, especially in genes highly expressed in the developing heart and brain. These mutations accounted for 20% of patients with CHD, NDD, and CA but only 2% of patients with isolated CHD. Mutations altered genes involved in morphogenesis, chromatin modification, and transcriptional regulation, including multiple mutations in RBFOX2, a regulator of mRNA splicing. Genes mutated in other cohorts examined for NDD were enriched in CHD cases, particularly those with coexisting NDD. These findings reveal shared genetic contributions to CHD, NDD, and CA and provide opportunities for improved prognostic assessment and early therapeutic intervention in CHD patients.
The third edition of Anesthesia for Congenital Heart Disease, the recognized gold-standard reference in this field, offers a major update and expansion of the textbook to reflect the ongoing ...development of the practice of pediatric and congenital cardiac anesthesia and the burgeoning knowledge base in this exciting field. Includes two new chapters addressing key areas; anesthetic and sedative neurotoxicity in the patient with congenital heart disease, and anesthesia in the patient with pulmonary hypertension Now in full color, with over 200 illustrations and photographs Multiple-choice questions accompany each chapter covering the most crucial learning points to optimize the learning experience for readers at all levels.
Holt–Oram syndrome (HOS) is a rare, autosomal dominant disorder caused by heterozygous pathogenic variants in cardiac T‐box transcription factor, TBX5. Classically, it is associated with upper limb ...malformations and variable cardiac abnormalities. Limb manifestations are considered to be invariably present, ranging in severity from limitation in movement, to triphalangeal thumbs, absent thumbs, shortened forearms, or phocomelia. Cardiac involvement is characterized by congenital heart defects, most commonly septal structural malformations, and conduction system disease. Recently, novel TBX5 variants have also been reported in association with dilated cardiomyopathy (DCM). In this context, we report eight individuals from four unrelated families, in whom pathogenic variants in TBX5 segregated with an atypical HOS phenotype. Affected individuals exhibit relatively mild skeletal features of HOS, with a predominant cardiac phenotype, which includes several individuals affected by non‐ischaemic DCM. To our knowledge, these represent the first reported cases of DCM in families with skeletal features of HOS, some of whom also harbored variants previously linked to a classical HOS phenotype (p. Arg279* and p.Arg237Gln). This finding supports diverse roles of TBX5 in cardiovascular development and function, and confirms the importance of long‐term cardiac surveillance for individuals affected by HOS. Furthermore, these families highlight the wide phenotypic variability of HOS, which may include comparatively mild upper limb findings in respect to cardiac manifestations.
TORCH infections Neu, Natalie; Duchon, Jennifer; Zachariah, Philip
Clinics in perinatology,
03/2015, Letnik:
42, Številka:
1
Journal Article
Recenzirano
TORCH infections classically comprise toxoplasmosis, Treponema pallidum, rubella, cytomegalovirus, herpesvirus, hepatitis viruses, human immunodeficiency virus, and other infections, such as ...varicella, parvovirus B19, and enteroviruses. The epidemiology of these infections varies; in low-income and middle-income countries, TORCH infections are major contributors to prenatal, perinatal, and postnatal morbidity and mortality. Evidence of infection may be seen at birth, in infancy, or years later. For many of these pathogens, treatment or prevention strategies are available. Early recognition, including prenatal screening, is key. This article covers toxoplasmosis, parvovirus B19, syphilis, rubella, hepatitis B virus, hepatitis C virus, and human immunodeficiency virus.
Congenital generalized lipodystrophy, type 1 (CGL1), due to biallelic pathogenic variants in AGPAT2, is characterized by the near total loss of body fat from the face, trunk, and extremities. ...Patients develop premature diabetes, hypertriglyceridemia, hepatic steatosis, and polycystic ovary syndrome. However, sparing of the facial fat and precocious pubertal development has not been previously reported in CGL1.
We report a 21-year-old woman of European descent with CGL1 who had sparing of the facial fat and premature thelarche at birth with premature pubarche and menstrual bleeding at age 3 years. Her serum 17-OH progesterone level rose to 1000 ng/dL (30.26 nmol/L) after cosyntropin stimulation test, suggestive of nonclassical congenital adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency. Hydrocortisone replacement therapy from age 3.5 to 10 years resulted in cessation of menstruation and growth of pubic hair, and a reduction of breast size. Sanger and whole-exome sequencing revealed compound heterozygous variants c.493-1G>C; p.(Leu165_Gln196del), and c.del366_588+534; p.(Leu123Cysfs*55) in AGPAT2 plus c.806G>C; p.(Ser269Thr) and c.844G>T; p.(Val282Leu) in CYP21A2. She developed diabetes at age 13 requiring high-dose insulin and had 7 episodes of acute pancreatitis due to extreme hypertriglyceridemia in the next 5 years. Metreleptin therapy was initiated at age 18 and after 3 years, she had remission of diabetes and hypertriglyceridemia; however, menstrual irregularity and severe hirsutism did not improve.
Concomitant NCAH in this CGL1 patient was associated with precocious pubertal development and sparing of facial fat. Metreleptin therapy drastically improved her hyperglycemia and hyperlipidemia but not menstrual irregularity and hirsutism.
Congenital heart defects constitute the most common human birth defect, however understanding of how these disorders originate is limited by our ability to model the human heart accurately in vitro. ...Here we report a method to generate developmentally relevant human heart organoids by self-assembly using human pluripotent stem cells. Our procedure is fully defined, efficient, reproducible, and compatible with high-content approaches. Organoids are generated through a three-step Wnt signaling modulation strategy using chemical inhibitors and growth factors. Heart organoids are comparable to age-matched human fetal cardiac tissues at the transcriptomic, structural, and cellular level. They develop sophisticated internal chambers with well-organized multi-lineage cardiac cell types, recapitulate heart field formation and atrioventricular specification, develop a complex vasculature, and exhibit robust functional activity. We also show that our organoid platform can recreate complex metabolic disorders associated with congenital heart defects, as demonstrated by an in vitro model of pregestational diabetes-induced congenital heart defects.
Although myopathies and neuromuscular junction disorders are typically distinct, their coexistence has been reported in several inherited and acquired conditions. Affected individuals have variable ...clinical phenotypes but typically display both a decrement on repetitive nerve stimulation and myopathic findings on muscle biopsy. Inherited causes include myopathies related to mutations in BIN1, DES, DNM2, GMPPB, MTM1, or PLEC and congenital myasthenic syndromes due to mutations in ALG2, ALG14, COL13A1, DOK7, DPAGT1, or GFPT1. Additionally, a decrement due to muscle fiber inexcitability is observed in certain myotonic disorders. The identification of a defect of neuromuscular transmission in an inherited myopathy may assist in establishing a molecular diagnosis and in selecting patients who would benefit from pharmacological correction of this defect. Acquired cases meanwhile stem from the co‐occurrence of myasthenia gravis or Lambert‐Eaton myasthenic syndrome with an immune‐mediated myopathy, which may be due to paraneoplastic disorders or exposure to immune checkpoint inhibitors.
Summary
These guidelines for the management of congenital ichthyoses have been developed by a multidisciplinary group of European experts following a systematic review of the current literature, an ...expert conference held in Toulouse in 2016 and a consensus on the discussions. They summarize evidence and expert‐based recommendations and are intended to help clinicians with the management of these rare and often complex diseases. These guidelines comprise two sections. This is part one, covering topical therapies, systemic therapies, psychosocial management, communicating the diagnosis and genetic counselling.
Linked Comment: Levy. Br J Dermatol 2019; 180:253.
Congenital and perinatal infections are a leading cause of neonatal and infant morbidity and mortality. Maternal screening, vaccines or treatment where available, constitute effective prevention ...strategies to reduce the burden of these diseases. Data on the burden of congenital and perinatal infections are very limited for low and middle-income regions.
This review aims to summarize the burden of congenital and perinatal infections and the main challenges for their control in resource-limited settings. Articles were identified through the main electronic databases and cover the period 1971-2016. Expert commentary: Estimates from low and middle-income countries indicate that the burden of congenital infections may be higher in these regions than in industrialized countries. As preventive and curative strategies are available to tackle some of these infections, efforts at the international and national levels must be made to implement those and thus reduce their burden in resource-limited countries.
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