Neonatal Characteristics of Children Conceived with In Vitro Fertilization or Intrauterine Insemination Compared to Sibling Births from Unassisted Conceptions.

Objective: To examine birth outcomes between children conceived with in vitro fertilization (IVF) or intrauterine insemination (IUI) compared with sibling births from unassisted conceptions.

Design: Retrospective sibling cohort SETTING: University health center fertility clinic PATIENT(S): Live born children conceived via IVF, with or without intracytoplasmic sperm injection (ICSI), or IUI at the Utah Center for Reproductive Medicine,1999 to 2018, and sibling births from unassisted conceptions (born 1985 to 2018). The main analysis included singleton births (460 IVF, 666 IUI, and 1,579 unassisted siblings).

Comorbidity and Multimorbidity in Adults With Congenital Heart Disease: Findings From a Multi-Site Population-Based Study.

Background: Survival of individuals with congenital heart disease (CHD) has improved, leading to a growing and aging population of adults living with these conditions. Over their lifetime, they often face an array of comorbidities that affect outcomes and complicate medical management. However, population-based information on such comorbidities is scarce, reducing opportunities for prevention.

Neonatal outcomes of pregnancy in women with congenital heart disease.

Background: Infants born to women with congenital heart disease (CHD) are at increased risk for adverse outcomes compared with the general population. There are few large, contemporary studies examining the relationship between CHD severity, maternal risk factors and neonatal outcomes.

Methods: Data on women with CHD who had a live birth from 2011 through 2014 in geographic areas in Georgia, North Carolina and Utah were analyzed.

Undiagnosed Hackathon Ends Diagnostic Odyssey in a Patient With DNA2-Related Rothmund-Thomson Syndrome.

Rothmund-Thomson syndrome (RTS) is an ultra-rare, genetically heterogeneous autosomal recessive genodermatosis characterized by poikiloderma, sparse hair and eyebrows, photosensitivity, and short stature. The recently described RTS type 4 (RTS-4), caused by biallelic variants in the DNA2 gene, is associated with additional distinctive features such as microphthalmia, corneal opacity, congenital cataracts (rather than juvenile), and hypothyroidism. To date, eight individuals with RTS-4 have been reported, all carrying a deep intronic variant in DNA2 (ENST00000358410.

A Rare Case of Neonatal Cholestasis Linked to FOCAD Gene Variants: Exploring the Variable Phenotypic Presentation and Its Implications.

Neonatal liver disease is a broad entity. When it presents in conjunction with other abnormalities, it raises the question of a potential underlying genetic cause. Etiologies that were once difficult to diagnose are becoming more readily identifiable with the arrival of next-generation sequencing.

Exome Sequencing to Identify Novel Susceptibility Genes for Nonsyndromic Split-Hand/Ft Malformation: A Report From the National Birth Defects Prevention Study.

Background: Split-hand/foot malformation (SHFM) is a rare, genetically heterogeneous, congenital limb defect. Some but not all associated genes are known; therefore, the aim was to identify genes underlying SHFM.

Methods: Buccal cell-derived DNA from 26 children with SHFM and their parents who participated in the National Birth Defects Prevention Study was exome sequenced.

Evaporation driven buckling of a drop laden with graphene oxide nanosheets.

The time-dependent shape of an evaporating spherical water drop containing graphene oxide (GO) nanosheets is measured for varying solid concentration, humidity level, and pH. The drop is sitting on a superhydrophobic surface, depinned from it. Three different stages of evaporation are identified: isotropic retraction of the drop interface, buckling of the shell of particles accumulated at the fluid interface, and shrinking of the buckled shell at constant shell shape.

Identification of 2 novel noncoding variants in patients with Diamond-Blackfan anemia syndrome by whole genome sequencing.

Diamond-Blackfan anemia syndrome (DBAS) is a rare congenital disorder with variable penetrance and expressivity and is characterized by pure red cell aplasia that typically manifests as early-onset chronic macrocytic or normocytic anemia and is often associated with other congenital anomalies. DBAS is etiologically heterogeneous with >20 known DBAS-associated genes that encode small and large ribosomal protein subunits and an inheritance pattern that is largely autosomal dominant or sporadic. We report 2 DBAS cases with previous negative genetic testing, which included targeted gene panels, karyotype analysis, chromosome breakage analysis, and whole exome sequencing.

Pushing the boundaries of rare disease diagnostics with the help of the first Undiagnosed Hackathon.

The first-ever Undiagnosed Hackathon was a groundbreaking event held by the Wilhelm Foundation, the Karolinska Undiagnosed Disease Program, and PhenoTips in collaboration with UDNI to solve medical mysteries and advance diagnostics for undiagnosed rare diseases. Nearly 100 healthcare professionals and researchers from 28 countries participated, working intensively for 48 hours to diagnose 10 families with undiagnosed rare diseases. This innovative approach to precision diagnostics highlighted the power of international, multidisciplinary collaboration and patient partnership, yielding promising results for patients seeking answers and benefiting the entire rare diseases community.

Regulatory elements in (7q21.3) locus contribute to genetic control of coronal nonsyndromic craniosynostosis and bone density-related traits.

Purpose: The etiopathogenesis of coronal nonsyndromic craniosynostosis (cNCS), a congenital condition defined by premature fusion of 1 or both coronal sutures, remains largely unknown.

Methods: We conducted the largest genome-wide association study of cNCS followed by replication, fine mapping, and functional validation of the most significant region using zebrafish animal model.

Results: Genome-wide association study identified 6 independent genome-wide-significant risk alleles, 4 on chromosome 7q21.

Cardiovascular disease risk factors in congenital heart disease survivors are associated with heart failure.

Background: Despite advances in treatment and survival, individuals with congenital heart defects (CHD) have a higher risk of heart failure (HF) compared to the general population.

Objective: To evaluate comorbidities associated with HF in patients with CHD with a goal of identifying potentially modifiable risk factors that may reduce HF-associated morbidity and mortality.

Methods: Five surveillance sites in the United States linked population-based healthcare data and vital records.

Equity in action: The Diagnostic Working Group of The Undiagnosed Diseases Network International.

Rare diseases are recognized as a global public health priority. A timely and accurate diagnosis is a critical enabler for precise and personalized health care. However, barriers to rare disease diagnoses are especially steep for those from historically underserved communities, including low- and middle-income countries.

Racial and Ethnic Disparities in Health Care Usage and Death by Neighborhood Poverty Among Individuals With Congenital Heart Defects, 4 US Surveillance Sites, 2011 to 2013.

Background: Socioeconomic factors may lead to a disproportionate impact on health care usage and death among individuals with congenital heart defects (CHD) by race, ethnicity, and socioeconomic factors. How neighborhood poverty affects racial and ethnic disparities in health care usage and death among individuals with CHD across the life span is not well described.

Methods And Results: Individuals aged 1 to 64 years, with at least 1 CHD-related () code were identified from health care encounters between January 1, 2011, and December 31, 2013, from 4 US sites.

Gastroschisis prevalence patterns in 27 surveillance programs from 24 countries, International Clearinghouse for Birth Defects Surveillance and Research, 1980-2017.

Background: Gastroschisis is a serious birth defect with midgut prolapse into the amniotic cavity. The objectives of this study were to evaluate the prevalence and time trends of gastroschisis among programs in the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR), focusing on regional variations and maternal age changes in the population.

Methods: We analyzed data on births from 1980 to 2017 from 27 ICBDSR member programs, representing 24 countries and three regions (Europe , Latin America, North America).

Buckling of a monolayer of platelike particles trapped at a fluid-fluid interface.

Particles trapped at a fluid-fluid interface by capillary forces can form a monolayer that jams and buckles when subject to uniaxial compression. Here we investigate experimentally the buckling mechanics of monolayers of millimeter-sized rigid plates trapped at a planar fluid-fluid interface subject to uniaxial compression in a Langmuir trough. We quantified the buckling wavelength and the associated force on the trough barriers as a function of the degree of compression.

Novel Variants and Cases of Acute Reversible Leukoencephalopathy and α-Ketoglutarate Accumulation and Literature Review.

Objectives: Acute reversible leukoencephalopathy with increased urinary alpha-ketoglutarate (ARLIAK) is a recently described autosomal recessive leukoencephalopathy caused by pathogenic variants in the gene. ARLIAK is characterized by acute neurologic involvement, often precipitated by febrile illness, with largely reversible clinical symptoms and imaging findings. Three patients have been reported in the literature to date.

Novel molecular mechanism in Malan syndrome uncovered through genome sequencing reanalysis, exon-level Array, and RNA sequencing.

The NFIX gene encodes a DNA-binding protein belonging to the nuclear factor one (NFI) family of transcription factors. Pathogenic variants of NFIX are associated with two autosomal dominant Mendelian disorders, Malan syndrome (MIM 614753) and Marshall-Smith syndrome (MIM 602535), which are clinically distinct due to different disease-causing mechanisms. NFIX variants associated with Malan syndrome are missense variants mostly located in exon 2 encoding the N-terminal DNA binding and dimerization domain or are protein-truncating variants that trigger nonsense-mediated mRNA decay (NMD) resulting in NFIX haploinsufficiency.

International Undiagnosed Diseases Programs (UDPs): components and outcomes.

Over the last 15 years, Undiagnosed Diseases Programs have emerged to address the significant number of individuals with suspected but undiagnosed rare genetic diseases, integrating research and clinical care to optimize diagnostic outcomes. This narrative review summarizes the published literature surrounding Undiagnosed Diseases Programs worldwide, including thirteen studies that evaluate outcomes and two commentary papers. Commonalities in the diagnostic and research process of Undiagnosed Diseases Programs are explored through an appraisal of available literature.

The burden, prevention and care of infants and children with congenital anomalies in sub-Saharan Africa: A scoping review.

The aim of this scoping review was to determine the scope, objectives and methodology of contemporary published research on congenital anomalies (CAs) in sub-Saharan Africa (SSA), to inform activities of the newly established sub-Saharan African Congenital Anomaly Network (sSCAN). MEDLINE was searched for CA-related articles published between January 2016 and June 2021. Articles were classified into four main areas (public health burden, surveillance, prevention, care) and their objectives and methodologies summarized.

Using a health observance event to raise awareness: An assessment of World Birth Defects Day.

World Birth Defects Day (WorldBDDay), observed annually on March 3, was launched in 2015 to advocate for public health surveillance, research, and prevention of birth defects, along with improved care and treatment for affected individuals. Following its fifth observance in 2019, we assessed WorldBDDay by analyzing: (a) engagement and content of over 2000 WorldBDDay posts on Facebook, Twitter, and Instagram; (b) interview responses from 9 WorldBDDay charter (founding) organizations on their perceptions of strengths and areas for improvement for WorldBDDay; (c) survey responses from 61 WorldBDDay 2019 partner (participating) organizations on their WorldBDDay 2019 activities; and (d) post-2019 social media engagement. Most social media posts (60%) occurred from organizations using Twitter (80% vs.

A novel variant resulting in Fanconi anemia identified in an infant with multiple congenital anomalies.

Fanconi anemia, FA, is a rare, multi-system disease caused by pathogenic variants in DNA repair genes. We report a novel variant in an infant with FA whose tracheobronchomalacia has not been described in FA. His severe presentation expands the phenotype of -associated FA, reported only in three patients previously.

Benefits of tailored disease management in improving tremor, white matter hyperintensities, and liver enzymes in a child with heterozygous X-linked ornithine transcarbamylase deficiency.

We report the case of a 19-month-old girl with late-onset ornithine transcarbamylase (OTC) deficiency initially referred to gastroenterology for intermittent vomiting lasting a year and abnormal liver enzymes (AST 730 U/L [reference range 26-55 U/L]; ALT 1213 U/L [reference range 11-30 U/L]) without hepatomegaly. While the patient was hospitalized for liver biopsy, intermittent tremors of the upper extremities with varying severity were noted. The patient was presumed to have hyperammonemia secondary to acute liver failure and was discharged after 5 days; follow-up monitoring led to readmission 7 days later.