Article
Pediatrics
L. Seddon, K. Dick, S. B. Carr, I. M. Balfour-Lynn
Summary: The majority of parents in a survey conducted in a London pediatric center believed that cystic fibrosis newborn screening results should be communicated face to face rather than over the telephone. There were mixed responses regarding whether parents should be informed of the genotype and CF diagnosis before the confirmatory sweat test.
EUROPEAN JOURNAL OF PEDIATRICS
(2021)
Article
Pediatrics
Iolo Doull, Christopher William Course, Ruth E. Hanks, Kevin W. Southern, Julian T. Forton, Lena P. Thia, Stuart J. Moat
Summary: The study aimed to determine the causes of false negative cases in CF newborn screening and found that the majority of false negatives were associated with poor quality DBS samples. Improving the quality of DBS samples would be the optimal way to enhance the sensitivity of the CF NBS programme.
ARCHIVES OF DISEASE IN CHILDHOOD
(2021)
Review
Pediatrics
Ioanna Loukou, Maria Moustaki, Konstantinos Douros
Summary: The aim of this study was to familiarize clinicians with the terms cystic fibrosis transmembrane conductance regulator related metabolic syndrome (CRMS) and cystic fibrosis screen positive inconclusive diagnosis (CFSPID), and to highlight the monitoring and outcomes of children with these designations. A literature review was performed to gather relevant articles, and the results showed that despite newborn screening programs for cystic fibrosis, the diagnosis remains uncertain for some infants. CRMS/CFSPID was established as a unified definition in 2016, but longer longitudinal studies are needed to determine the appropriate follow-up for these children. It is important for pediatricians to be knowledgeable about this condition and for children to be in contact with their local CF center.
Review
Biology
Joan Kathleen DeCelie-Germana, Lynn Bonitz, Elinor Langfelder-Schwind, Catherine Kier, Barry Lawrence Diener, Maria Berdella
Summary: As of December 2009, cystic fibrosis (CF) newborn screening (NBS) is performed in all 50 US states and the District of Columbia. Widespread implementation of CF newborn screening (CFNBS) in the US and internationally has brought about new and varied challenges. Advances in genetic testing have provided an opportunity for earlier identification of babies with CF through CFTR sequencing, improving long-term outcomes through prompt treatment and intervention.
Article
Pediatrics
Heather J. Stalker, Amy R. Jonasson, Sidney M. Hopfer, Melanie Sue Collins
Summary: Genetic counseling through telemedicine was well received by families, leading to improved understanding of CF-related risks for their child and other family members. The study also showed that parents demonstrated better comprehension of the genetic implications of an abnormal CF newborn screen after receiving counseling via telemedicine. Additionally, the use of trained CF genetic counselors through telemedicine proved to be feasible and effective in improving parent understanding of CF genetics across a wide geographical area.
PEDIATRIC PULMONOLOGY
(2023)
Article
Pediatrics
Tugba Ramasli Gursoy, Pelin Asfuroglu, Tugba Sismanlar Eyuboglu, Ayse Tana Aslan, Asli Imran Yilmaz, Gokcen Unal, Busra Sultan Kibar, Sevgi Pekcan, Melih Hangul, Mehmet Kose, Isil Irem Budakoglu, Deniz Acican
Summary: This cross-sectional study aimed to evaluate the cutoff values of immunoreactive trypsinogen (IRT) and investigate the relationship between IRT values and clinical characteristics in children with cystic fibrosis (CF). The study included data from children with positive newborn screening (NBS) from 2015 to 2021. Sensitivity and specificity of IRT cutoff values were assessed, and the positive predictive value (PPV) was determined. The study found that while the sensitivity of CF NBS was high, the PPV was significantly lower than expected. Revising the NBS strategy may help overcome false-positive results.
EUROPEAN JOURNAL OF PEDIATRICS
(2023)
Article
Genetics & Heredity
Sevcan Tug Bozdogan, Cem Mujde, Ibrahim Boga, Ozge Sonmezler, Abdullah Hanta, Cagla Rencuzogullari, Dilek Ozcan, Derya Ufuk Altintas, Atil Bisgin
Summary: This study evaluates the genetic testing results of 1595 newborns in Turkey with positive CF NBS program results, showing that 35.1% of patients carried at least one CF-related variant. The most common findings included compound heterozygosity for two mutations and the identification of novel variants. The study highlights the impact of NBS on genetic diagnosis centers and the diversity of CFTR mutations in the Turkish population.
Article
Critical Care Medicine
Mirjam Stahl, Eva Steinke, Simon Y. Graeber, Cornelia Joachim, Christoph Seitz, Hans-Ulrich Kauczor, Monika Eichinger, Susanne Haemmerling, Olaf Sommerburg, Mark O. Wielpuetz, Marcus A. Mall
Summary: The study showed that MRI can detect the progression of lung disease and the benefits of early diagnosis using NBS in preschool children with CF. Increase in MRI global score was associated with symptoms like cough and pulmonary exacerbations. MRI is suggested as a sensitive outcome measure for diagnostic monitoring and early intervention trials in preschool children with CF.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2021)
Article
Pediatrics
Michael J. J. Rock, Mei Baker, Nicholas Antos, Philip M. M. Farrell
Summary: Using next generation sequencing (NGS) in combination with immunoreactive trypsinogen (IRT) can effectively identify infants at risk for cystic fibrosis (CF) without significantly increasing the rate of detecting carriers. NGS has the potential to enhance equity, sensitivity, and detection of more CF patients with 2 variants during the screening process.
PEDIATRIC PULMONOLOGY
(2023)
Article
Pediatrics
Annemarie G. Wolfe, Stephanie P. Gilley, Stephanie W. Waldrop, Christina Olson, Emma Harding, Kaitlin Widmer, Lindsey B. Gumer, Matthew Haemer, Jordana E. Hoppe
Summary: Universal newborn screening has changed the way CF is diagnosed, with nearly all cases being detected shortly after birth. However, clinicians should still be aware of the possibility of CF in newborns with normal screening results.
FRONTIERS IN PEDIATRICS
(2023)
Article
Respiratory System
Susanna A. McColley, Stacey L. Martiniano, Clement L. Ren, Marci K. Sontag, Karen Rychlik, Lauren Balmert, Alexander Elbert, Runyu Wu, Philip M. Farrell
Summary: This study evaluated whether the implementation of cystic fibrosis newborn screening leads to equitable timeliness of initial evaluation. The study compared the age at the first event (AFE) between infants of different races and ethnicities (Group 1) and white non-Hispanic infants (Group 2). The study found that differences in AFE for infants with CF from historically marginalized groups may exacerbate long-standing health disparities.
JOURNAL OF CYSTIC FIBROSIS
(2023)
Article
Computer Science, Information Systems
Rosario R. Ricalde, Jonathan G. Fabia, Carlos Diego A. Rozul, Maria Rina T. Reyes Quintos, Raymond Francis R. Sarmiento
Summary: The study aimed to assess the usability of the online and offline versions of the Philippine Electronic National Newborn Hearing Screening Registry (ENNHSR) and examine user perspectives and satisfaction with the training modules and system. The study involved the development of the ENNHSR systems, training modules, evaluation of the user manual, and conducting user training sessions. The results showed positive feedback from participants and identified areas for improvement.
INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS
(2022)
Article
Pediatrics
Halime Nayir Buyuksahin, Nagehan Emiralioglu, Beste Ozsezen, Dilber Ademhan Tural, Birce Sunman, Ismail Guzelkas, Basak Tezel, Didem Dayangac Erden, Ebru Yalcin, Deniz Dogru, Ugur Ozcelik, Nural Kiper
Summary: The study found low sensitivity and positive predictive value of NBS for cystic fibrosis, with infants who tested negative showing symptoms such as feeding reluctance and Pseudobartter syndrome. Early diagnosis did not significantly impact nutritional outcomes, highlighting the need for further large-scale studies to optimize care for infants diagnosed through NBS.
PEDIATRIC PULMONOLOGY
(2022)
Article
Pediatrics
Kathrine Baldwin, Erin McElroy Barker, Mary Carayannopoulos, Philip M. Farrell, Robert Zanni, Thomas F. Scanlin
Summary: The study found that some children with cystic fibrosis were missed in the 20-year IRT/DNA (F508del) algorithm, highlighting the need for quality improvement measures to prevent future delayed diagnoses.
PEDIATRIC PULMONOLOGY
(2023)
Article
Public, Environmental & Occupational Health
Felicity Boardman, Corinna Clark
Summary: This study explores the perspectives of parents who received positive results from cystic fibrosis (CF) screening and finds that the positive results have a disruptive impact on their lives. For families with CF, the results change their way of life and emphasize familial bonds. For families with uncertain results, the uncertainty becomes a barrier to entry into different social environments.
SOCIAL SCIENCE & MEDICINE
(2022)
Article
Psychology, Developmental
Emma K. Baker, Sheena Arora, David J. Amor, Perrin Date, Meagan Cross, James O'Brien, Chloe Simons, Carolyn Rogers, Stephen Goodall, Jennie Slee, Chris Cahir, David E. Godler
Summary: This study compared the costs associated with raising a child with four rare disorders (Prader-Willi, Angelman, Chromosome 15q Duplication, and fragile X syndromes) and examined the relationship between these costs and clinical severity. The study found that intellectual functioning negatively predicted total costs, and the impact of intellectual functioning on total costs was significantly different in individuals with Angelman syndrome compared to other syndromes.
JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
(2023)
Article
Ethics
Hilary Bowman-Smart, Christopher Gyngell, Cara Mand, David J. Amor, Martin B. Delatycki, Julian Savulescu
Summary: The article discusses the potential use of noninvasive prenatal testing (NIPT) for testing non-medical traits, presenting arguments against and in favor of permitting such use. The objections to permitting these uses include practical problems and negative impacts on the child, family, and society, while the arguments for permitting them include reproductive liberty and autonomy, as well as the principle of procreative beneficence.
AMERICAN JOURNAL OF BIOETHICS
(2023)
Article
Obstetrics & Gynecology
Karin Hammarberg, Jane Halliday, Joanne Kennedy, David P. Burgner, David J. Amor, Lex W. Doyle, Markus Juonala, Sarath Ranganathan, Liam Welsh, Michael Cheung, Robert McLachlan, John McBain, Sharon Lewis
Summary: The study explores the impact of assisted reproductive technology (ART) conception and psychosocial factors on the quality of life of adults. It finds that being ART-conceived can confer advantages in quality of life in adulthood.
Article
Genetics & Heredity
Lottie D. Morison, Elisabeth Meffert, Miriam Stampfer, Irene Steiner-Wilke, Brigitte Vollmer, Katrin Schulze, Tracy Briggs, Ruth Braden, Adam Vogel, Daisy Thompson-Lake, Chirag Patel, Edward Blair, Himanshu Goel, Samantha Turner, Ute Moog, Angelika Riess, Frederique Liegeois, David A. Koolen, David J. Amor, Tjitske Kleefstra, Simon E. Fisher, Christiane Zweier, Angela T. Morgan
Summary: Disruptions of FOXP2 can cause severe speech disorder known as childhood apraxia of speech (CAS). This study examined individuals with pathogenic FOXP2-only variants and found that speech disorders, including CAS, were prevalent in these cases. Other comorbidities such as feeding difficulties, motor impairment, anxiety, depression, and sleep disturbance were also observed. The study emphasizes the importance of FOXP2 in understanding the neurobiological basis of speech disorder.
JOURNAL OF MEDICAL GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Antony Kaspi, Michael S. Hildebrand, Victoria E. Jackson, Ruth Braden, Olivia van Reyk, Tegan Howell, Simone Debono, Mariana Lauretta, Lottie Morison, Matthew J. Coleman, Richard Webster, David Coman, Himanshu Goel, Mathew Wallis, Gabriel Dabscheck, Lilian Downie, Emma K. Baker, Bronwyn Parry-Fielder, Kirrie Ballard, Eva Harrold, Shaun Ziegenfusz, Mark F. Bennett, Erandee Robertson, Longfei Wang, Amber Boys, Simon E. Fisher, David J. Amor, Ingrid E. Scheffer, Melanie Bahlo, Angela T. Morgan
Summary: This study identified new candidate genes associated with childhood apraxia of speech (CAS) through genome sequencing and bioinformatic analysis. The findings highlight the roles of chromatin organization and gene regulation in CAS, and confirm co-expression of CAS-related genes during brain development.
MOLECULAR PSYCHIATRY
(2023)
Article
Genetics & Heredity
Emma K. Baker, Marta Arpone, Minh Bui, Claudine M. Kraan, Ling Ling, David Francis, Mathew F. Hunter, Carolyn Rogers, Michael J. Field, Lorena Santa Maria, Victor Faundes, Bianca Curotto, Paulina Morales, Cesar Trigo, Isabel Salas, Angelica M. Alliende, David J. Amor, David E. Godler
Summary: This study found significant associations between FMR1 methylation levels in blood and buccal epithelial cells and FMR1 mRNA levels and intellectual functioning in males with FXS, with stronger relationships seen using MS-QMA compared to mSB.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Genetics & Heredity
Melanie Leffler, Louise Christie, Anna Hackett, Bruce Bennetts, Himanshu Goel, David J. Amor, Greg B. Peters, Michael Field, Tracy Dudding-Byth
Summary: The low copy tandem repeat area at Xq28 is prone to recurrent copy number gains, including the K/L mediated duplications of 300 kb size (herein described as the K/L mediated Xq28 duplication syndrome). We describe five families, including nine males with K/L mediated Xq28 duplications, some with regions of greater copy number variation (CNV). We summarise findings in 25 affected males reported to date.
Article
Biochemistry & Molecular Biology
Miya St John, Olivia van Reyk, David A. Koolen, Bert B. A. de Vries, David J. Amor, Angela T. Morgan
Summary: This study provides a detailed characterization of speech and language impairment in Koolen-de Vries syndrome (KdVS). It defines the medical and neurodevelopmental phenotype in the largest cohort of KdVS individuals to date, highlighting the core features of intellectual disability, eye anomalies, structural brain anomalies, and dental problems. While most individuals with KdVS can speak, some use augmentative and alternative communication methods. The study also reveals relative weaknesses in language, literacy, and social skills, and relative strengths in social competence and coping skills.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Biochemistry & Molecular Biology
David I. Francis, Zornitza Stark, Ingrid E. Scheffer, Tiong Yang Tan, Krithika Murali, Lyndon Gallacher, David J. Amor, Himanshu Goel, Lilian Downie, Chloe A. Stutterd, Emma I. Krzesinski, Anand Vasudevan, Ralph Oertel, Vida Petrovic, Amber Boys, Vivian Wei, Trent Burgess, Karen Dun, Karen L. Oliver, Anne Baxter, Anna Hackett, Samantha Ayres, Sebastian Lunke, Paul Kalitsis, Meaghan Wall
Summary: This study aimed to compare the diagnostic yield of saliva and blood for pathogenic copy number variants (CNVs). The results showed that saliva microarray testing had increased diagnostic utility over blood testing in individuals with syndromic intellectual disability (ID). Mosaic pathogenic CNVs or aneuploidy were detected in saliva but not in blood.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Review
Biochemistry & Molecular Biology
Erin Crellin, Melissa Martyn, Belinda McClaren, Clara Gaff
Summary: Patient care experiences play a crucial role in the successful implementation of genomics in paediatric care. A scoping review was conducted to understand parents' experiences and needs regarding genetic testing for rare diseases in their children. The review revealed that parents valued feeling cared for, consistent relationships with clinicians, empathic communication, updated information during the waiting period for test results, and access to support resources following result disclosure. Strategies to address unmet needs were proposed, but evidence on their effectiveness was limited. This emphasizes the need for rigorous interventions and the integration of genomics into paediatric care.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Article
Genetics & Heredity
Amy Nisselle, Emily King, Bronwyn Terrill, Belinda Davey, Belinda McClaren, Kate Dunlop, Debra Graves, Sylvia Metcalfe, Clara Gaff
Summary: Genomic medicine is being implemented globally, and a genomic-competent health workforce is needed. A survey of Australian non-genetics physicians revealed that confidence and engagement with genomic medicine were influenced by factors such as specialty, continuing genomics education, and genomics research experience. Respondents who had completed genomics education and were engaged in genomic medicine reported higher confidence and were more likely to prefer genomic testing with genetics services support. A progression of genomic competence aligned with service delivery models and workplace learning could facilitate the adoption of genomic tests.
NPJ GENOMIC MEDICINE
(2023)
Article
Clinical Neurology
Renee Smyth, Susan M. Reid, Kate Paton, Angela T. Guzys, Claire E. Wakefield, David J. Amor
Summary: The aim of this study was to understand parents' beliefs about the causes of cerebral palsy (CP) and the emotions related to those beliefs. A survey was conducted on 226 parents of children with CP aged 1 to 18 years. The majority of participants expressed the importance of understanding the causes of CP, but there was also uncertainty about the causes. The most commonly endorsed causal factors were intrapartum hypoxia, brain damage, and preterm birth, and parents often experienced feelings of anger, sadness, guilt, and confusion.
DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY
(2023)
Article
Genetics & Heredity
Linda M. Reis, David J. Amor, Raad A. Haddad, Catherine B. Nowak, Kim M. Keppler-Noreuil, Smith Ann Chisholm, Elena V. Semina
Summary: Axenfeld-Rieger anomaly is an ocular disorder associated with other systemic abnormalities. This study identified pathogenic variants in nine families affecting five different genes/regions. USP9X and JAG1 were the most commonly mutated genes associated with the disorder. Variants in CDK13, BCOR, and an X chromosome deletion were also found to be linked with Axenfeld-Rieger syndrome.
Article
Biochemistry & Molecular Biology
David E. Godler, Yoshimi Inaba, Minh Q. Bui, David Francis, Cindy Skinner, Charles E. Schwartz, David J. Amor
Summary: This study characterizes the specific DNA methylation patterns of fragile X syndrome in blood and brain tissues, providing a novel avenue for the detection of the syndrome through DNA methylation analysis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Erin Turbitt, Meg Bourne, Alison McEwen, David J. Amor
Summary: This study investigated parents' preferences and motivations for acquiring and discussing prognostic genetic test results. The findings showed that parents had varying levels of tolerance for prognostic uncertainty and focused more on their child's potential and challenges. However, they also expressed concerns about the potential loss of hope and societal stigma associated with prognostic information.
DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY
(2023)
Article
Genetics & Heredity
Katerina S. Kucera, Beth Lincoln Boyea, Brooke Migliore, Sarah Nelson Potter, Veronica R. Robles, Oksana Kutsa, Heidi Cope, Katherine C. Okoniewski, Anne Wheeler, Catherine W. Rehder, Edward C. Smith, Holly L. Peay
Summary: Screening for elevated CK-MM levels in dried blood spots is a feasible method to identify newborns with DMD. Including specific cutoffs, repeat testing, and genetic sequencing can improve the accuracy and sensitivity of screening.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Madeline Currey, Ilana Solomon, Sarah Mcgraw, Jenny Shen, Francisco Munoz, Ernesto Sosa, Vanessa Puello-Lozano, Sam Wing, Lisa Lopez, Michelle Afkhami, Janine Lobello, Szabolcs Szelinger, Stacy W. Gray
Summary: This study conducted qualitative interviews with cancer patients and providers to identify gaps in clinical care and propose care delivery solutions for the return of secondary germline findings. The responses of patients varied depending on the amount of pre-test counseling they received, and providers identified insufficient clinic time as a major barrier to pretest education. Online support tools and standardized pre-test education models were favored by providers. There were differing perspectives on how pre-test education should be integrated into clinical workflows, but agreement on the inclusion of differences between somatic and germline testing, likelihood of medically actionable findings, and the possibility of being referred to a genetics provider.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Kiely N. James, Shimul Chowdhury, Yan Ding, Sergey Batalov, Kelly Watkins, Yong Hyun Kwon, Lucitia Van Der Kraan, Katarzyna Ellsworth, Stephen F. Kingsmore, Lucia Guidugli
Summary: This study used genome sequencing to detect a wide range of copy-number variants (CNVs) and other non-single nucleotide variant/indel variant types. These genetic alterations accounted for 15.8% of reported variants, with deletions being the most common type. The study also found that additional genetic tests were ordered in some cases, but failed to report the variants detected by genome sequencing.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Asem Berkalieva, Nicole R. Kelly, Ashley Fisher, Samuel F. Hohmann, Monisha Sebastin, Miranda Di Biase, Katherine E. Bonini, Priya Marathe, Jacqueline A. Odgis, Sabrina A. Suckiel, Michelle A. Ramos, Rosamond Rhodes, Noura S. Abul-Husn, John M. Greally, Carol R. Horowitz, Melissa P. Wasserstein, Eimear E. Kenny, Bruce D. Gelb, Bart S. Ferket
Summary: The study aims to understand the effects of returning diagnostic sequencing results on clinical actions and economic outcomes for pediatric patients with suspected genetic disorders. The results showed that patients with positive findings were more likely to receive specialist consultation, but there were no significant increases in overall physician services and costs. More large-scale studies are needed to confirm these findings.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Kirstine Stochholm, Camilla Holmgard, Shanlee M. Davis, Claus H. Gravholt, Agnethe Berglund
Summary: This study assessed the incidence, prevalence, and age at diagnosis of individuals with 45,X/46,XY mosaicism and described the associated mortality pattern. The study found an increasing incidence of 45,X/46,XY mosaicism in males and a stable incidence in females. Males were diagnosed at an older age than females. Additionally, 45,X/46,XY mosaicism was associated with increased all-cause mortality.
GENETICS IN MEDICINE
(2024)
Article
Genetics & Heredity
Yunjia Chen, Ender Karaca, Nathaniel H. Robin, Dana Goodloe, Ali Al-Beshri, S. Joy Dean, Anna C. E. Hurst, Andrew J. Carroll, Fady M. Mikhail
Summary: This study confirms the association between DLG2 intragenic deletions and neurodevelopmental disorders, supports the haploinsufficiency of the DLG2 gene, and suggests a potential association between these deletions and congenital anomalies and dysmorphism.
GENETICS IN MEDICINE
(2024)
