Pediatric Geneticists Research Articles

Evaluating the impact of accessible low-cost pediatric genetic testing on underserved communities in the United States.

Genetic testing is at the forefront of medical diagnosis, management, and preventative care particularly within the field of nephrology, but such testing can be prohibitively expensive for patients from disadvantaged backgrounds. This study is aimed at exploring how use of a low-cost, comprehensive commercial panel could increase availability of genetic testing to patients served by an inner-city American hospital and overcome many of the obstacles faced by these patients, including lack of availability of pediatric geneticist and genetic counselors, leading to delay in care and management, cost of genetic testing, and inaccessibility of genetic testing to underserved populations. Single-center retrospective analysis patients who underwent genetic testing with NATERA Renasight Kidney Gene Panels run between November 2020 and October 2021. Genetic testing was offered to 208 patients, with 193 tests performed, 10 pending, and 4 deferred. Seventy-six patients were found to have results of clinical significance; 117 patients were found to have a negative result, of which 79 were found to have a variant of unknown significance (VUS); and 8 of these 79 VUS were later determined to be clinically significant leading to a change in management. Patient payment data breakdown showed that of 173, 68% used public insurance coverage, 27% used commercial or private insurance, and 5% were unknown. Genetic testing with the NATERA Renasight Panel provided a high positivity rate for genetic testing using next generation sequencing. It also allowed us to provide access to genetic testing to a larger population, specifically underserved and underrepresented patients. A higher resolution version of the Graphical abstract is available as Supplementary information.

The experience of one pediatric geneticist with telemedicine-based clinical diagnosis.

Telemedicine has long been considered as an attractive alternative methodology in clinical genetics to improve patient access and convenience. Given the importance of the dysmorphology physical examination and anthropometric measurement in clinical genetics, many have wondered if lost information would hamper diagnosis. We previously addressed this question by analyzing thousands of diagnostic encounters in a single practice involving multiple practitioners and found no evidence for a difference in new molecular diagnosis rates. However, our previous study design resulted in variability in providers between in-person and telemedicine evaluation groups. To address this in our present study, we expanded our analysis to 1104 new patient evaluations seen by one highly experienced clinical geneticist across two 10-month periods before and after the start of the COVID-19 pandemic. Comparing patients seen in-person to those seen by telemedicine, we found significant differences in race and ethnicity, preferred language, and home zip code median income. The clinical geneticist intended to send more genetic testing for those patients seen by telemedicine, but due to issues with test authorization and sample collection, there was no difference in ultimate completion rate between groups. We found no significant difference in new molecular diagnosis rate. Overall, we find telemedicine to be an acceptable alternative to in-person evaluation for routine pediatric clinical genetics care.

Evaluation of social cognition, autistic traits, and dysmorphology in comorbid specific learning disorder and attention-deficit/hyperactivity disorder.

Research on areas such as social cognition, autistic traits, and minor physical anomalies in comorbid Specific Learning Disorder (SLD) and attention-deficit/hyperactivity disorder (ADHD) is limited. In this study, we compared these areas in children aged between 8 and 14 with comorbid SLD and ADHD and their typically developed peers. Emotion recognition and social cognition were evaluated by Faces Test, Reading the Mind in the Eyes Test, Comprehension Test, and Difficulties in Emotion Regulation Scale. Autism Spectrum Screening Questionnaire and Social Responsiveness Scale were used for screening of autism spectrum disorder in children. Furthermore, autistic traits in parents were measured by Autism-Spectrum Quotient. The MPAs of all the subjects were determined by pediatric geneticists. We detected that children with comorbid SLD and ADHD performed worse than controls in all social cognition tests and maternal AQ score had a strong correlation with the Faces Test, DERS, and SRS scores. Also, the total ASSQ score in the comorbid SLD and ADHD group was significantly higher than controls. Finally, MPAs were significantly more frequent in the comorbid SLD and ADHD group. Impairment in social cognition and evaluation of autistic traits and dysmorphology in children with comorbid SLD and ADHD may provide useful information on neurodevelopmental disorders.

EP249: Practical implementation of inpatient rapid comprehensive sequencing for critically ill pediatric patients

The utility of inpatient rapid exome and genome sequencing has been well documented, but implementation continues to be hampered by inadequate insurance reimbursement, clinical genetics support availability, and high costs. Since late 2019, CS Mott Children’s Hospital at the University of Michigan has implemented a process through which critically ill pediatric patients can be evaluated with rapid comprehensive sequencing. After consideration of pre-determined criteria, each case is proposed by a consulting Pediatric Geneticist and then promptly evaluated by a multi-disciplinary committee (including Pediatric Geneticists, Cardiologist, Pediatric and Neonatal intensivists, and Neurologist).

PH Roundtable: Genetics and Pulmonary Hypertension

PH Roundtable: Genetics and Pulmonary Hypertension

What is a Pediatric Geneticist?

Patient Education| 2021 What is a Pediatric Geneticist? Connected Content Translation: ¿Qué es un Geneticista Pediátrico?: (What is a Pediatric Geneticist?) Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Share Icon Share Facebook Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation What is a Pediatric Geneticist?. Pediatric Patient Education 2021; 10.1542/peo_document156 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search nav search search input Search input auto suggest search filter All AAP SitesAll PublicationsPediatric Patient Education Search Advanced Search Subjects: Pediatric Specialist Handouts Topics: academic medical centers, academic performance, achondroplasia, brain development, congenital abnormality, congenital heart disease, cystic fibrosis, disability, down syndrome, fetal alcohol syndrome Fortunately, most children are born healthy with no medical problems or birth defects. However, some children are born with differences in body structure, brain development, or body chemistry that can lead to problems with health, development, school performance, and/or social interaction. Pediatric Geneticists are trained to identify the causes and natural history of these disorders. They may suggest tests and treatments that can help in understanding and caring for your child's condition. Pediatric geneticists also can help families understand whether some conditions are hereditary (coming from the genes) and offer testing to family members who may be at risk for having children with similar problems. Pediatric geneticists are medical doctors who have had Four years of medical schoolAt least 2 years of residency training in pediatricsAt least 2 years of additional specialty training in medical geneticsCertification from the American... Copyright © 20022002American Academy of Pediatrics You do not currently have access to this content.

Redeployment: Tales of a pediatric geneticist in a COVID-19 combat zone.

The author has no conflicts of interest to disclose. Data sharing is not applicable to this article as no new data were created or analyzed in this study.

Organisation de la prise en charge d’une maladie osseuse constitutionnelle lors de la transition de l’enfance à l’âge adulte

Rare skeletal dysplasias concern more than 400 different entities (more than 364 genes involved), and affect one person in 5000 all etiologies combined. Transitional care is an intentional, progressive, and coordinated process to accompany patients from pediatric care to an adult medical system. It must be distinguished from transfer, which refers to the exact point in time when the responsibility for patient care shifts from the pediatrician to the adult's physician and is only part of the transition. The absence of carefully planned transition may lead to loss of care. The transition to a new care system is particularly important in patients with skeletal dysplasias, characterized by various degrees of skeletal deformities, joint limitations, scoliosis, and bone fragility, which need specialized care in order to prevent a decrease in function level and potentially severe complications in adulthood, and to maintain patients’ health status. To improve the continuity of medical and surgical care from a pediatric to an adult system were created in 2005 transitional consultations with pediatric geneticist–orthopedic binomials in adult sites and a national protocol of care was developed by the skeletal dysplasias reference center. The referent pediatrician or orthopedic surgeon prepares patients to the transition phase and chooses the appropriate timing for the transfer consultation. Success depends on appropriate timing, and progressive transfer involving both pediatric and adult physicians. New strategies are necessary to avoid loss of care.

Inherited Epidermolysis Bullosa – A Case Report of Several Family Members in Three Generations

Abstract Inherited epidermolysis bullosa (IEB) is a genodermatosis transmitted in either autosomal dominant or autosomal recessive manner. The disease is characterized by the development of blisters, erosions, scars, nail dystrophy and scalp abnormalities. Our case report has included four members of one family in three generations with manifested disease. Our 25-year-old female patient presented with a few eroded, crusted, nummular lesions localized on the dorsal plate of interphalangeal joints of fingers, elbow and knee skin, while anonychia was found on her digits. Our youngest patient (her 3.5-year-old son) presented with the lesions in the form of blisters filled with serous fluid, erosions, recent scars and atrophy. Some atrophic scars on the elbow and knee skin were found in our patient′s younger brother, aged 16. The 46-year-old mother of our female patient had nail dystrophy on her hands accompanied by the toenails absence. Pediatric geneticist created the pedigree chart which showed autosomal dominant inheritance pattern with complete expressivity and penetrance. Further diagnostics was not done because the family was not interested.

The Time-Consuming Demands of the Practice of Medical Genetics in the Era of Advanced Genomic Testing

Clinical genetics services are time- and labor-intensive. With increasing pressure for cost-effective medical care, the means of providing medical genetics services need to be evaluated in the current era of new genomic technologies.An anonymous online survey regarding activities linked to medical genetics practice was administered to an international cohort of professionals. Among 151 responses, the reported average time required for pediatric, oncogenetic, pregnancy with a malformed fetus, and preamniocentesis counseling sessions was 48, 37, 40, and 18 min, respectively. The time required to prepare a summary letter followed a similar pattern. Professionals with less experience needed more time for specific activities. The time required for the total workup of a pediatric patient ranged from 1 h and 48 min to 4 h, most of which was associated with indirect activities. Professionals performing one type of consultation (74% pediatric geneticists) perform fewer consultations per week. Respondents’ narrative comments reflected the complexity of the work and challenges faced.Clinical genetics is a time-consuming profession with increased demands related to advanced genetic and genomic testing.We will discuss further consideration to suggest how to adapt these changes to the demands of cost-effectiveness without compromising the quality of patient care.

Role of Pediatric Geneticists in Craniofacial Teams: The Identification of Craniofacial Conditions with Cancer Predisposition

Journal of Pediatrics, The - In Press.Proof corrected by the author Available online since jeudi 9 juin 2016

The time-consuming demands of the practice of medical genetics in the era of advanced genomic testing.

Clinical genetics services are time- and labor-intensive. With increasing pressure for cost-effective medical care, the means of providing medical genetics services need to be evaluated in the current era of new genomic technologies. An anonymous online survey regarding activities linked to medical genetics practice was administered to an international cohort of professionals. Among 151 responses, the reported average time required for pediatric, oncogenetic, pregnancy with a malformed fetus, and preamniocentesis counseling sessions was 48, 37, 40, and 18 min, respectively. The time required to prepare a summary letter followed a similar pattern. Professionals with less experience needed more time for specific activities. The time required for the total workup of a pediatric patient ranged from 1 h and 48 min to 4 h, most of which was associated with indirect activities. Professionals performing one type of consultation (74% pediatric geneticists) perform fewer consultations per week. Respondents' narrative comments reflected the complexity of the work and challenges faced. Clinical genetics is a time-consuming profession with increased demands related to advanced genetic and genomic testing. Further consideration is required to determine how to adapt these changes to the demands of cost-effectiveness without compromising the quality of patient care.Genet Med 18 4, 372-377.

Abstract 08: Clinical exome sequencing in the diagnosis of pediatric cancer predisposition

Abstract Background: Currently, there are few guidelines on genetic testing of pediatric patients for cancer predisposition and on appropriate cancer surveillance recommendations once a genetic cancer predisposition is diagnosed. Previous research studies estimated that only about 5-10% of pediatric cancers are due to a heritable cause. However, this may be an underestimation of the true incidence in the pediatric population where most patients being diagnosed with cancer do not have a significant history of environmental risk exposures, such as smoking or ultra-violet sun exposure. Methods: We have created a multi-disciplinary Pediatric Cancer Predisposition Clinic at the University of California, Los Angeles (UCLA) that serves dual research and clinical missions of taking care of pediatric patients at an increased risk of cancer due to a genetic condition and advancing our understanding of cancer predisposition. Each family meets with a pediatric geneticist, pediatric oncologist, and genetic counselor for pre- and post- test counseling. We also consider the medical and psychosocial effects of these analyses on not only the patient, but also the parents of our patients, as well as direct relatives, who are affected and may need cancer surveillance. When indicated, we use Clinical Exome Sequencing (CES) through the UCLA Clinical Genomics Center, as our first-line diagnostic test due to the unusual presentation of the many inherited cancer susceptibility genes in childhood. This single test assays 95% of all protein-coding sequence of current clinically offered disease genes and is usually more efficient and cost-effective than single-gene or panel testing, and data are saved for re-interpretation. We then formulate individualized cancer surveillance recommendations and coordinate all tests with the family and general pediatrician. Results: There were 32 patients evaluated in the first 14 months. The average age of the patients was 10 years. Thirty-one referrals were from within our institution. Two patients had a history of cancer and presented with known familial cancer predisposition syndromes (Rhabdoid tumor predisposition and Hereditary paraganglioma-pheochromocytoma syndromes). Six additional patients presented without a personal history of cancer but with a known genetic syndrome associated with an increased cancer risk (Gorlin, Bannayan-Riley-Ruvalcaba, Cowden, Li-Fraumeni, Beckwith-Wiedemann, and Von Hippel-Lindau syndromes). Four patients were referred with known familial mutations in the family and had positive confirmatory testing (Li-Fraumeni, Familial adenomatous polyposis, and two with Neurofibromatosis Type 1). One patient was referred with a known mutation in the family and had negative testing (Hyperparathyroidism-jaw tumor syndrome). Nineteen patients had a family history indicative of familial early-onset cancer as well as a personal history of cancer and had CES was ordered. Of these, CES resulted in two reportable, likely pathogenic mutations in PTEN and NF-1. Four patients had no clinically significant genetic variants identified, 11 patients had variants of uncertain clinical significance, and two patients' results are pending. Conclusion: More thorough and broad scale germline analyses are needed to accurately inform patients of inherited risk to cancer, as it is not always obvious based on clinical presentation or family history. Our findings demonstrate a significant number of genomic variants with uncertain but potentially relevant clinical significance that warrant further study. CES is already a routinely used tool for mendelian genetic syndromes, and its routine use in testing the germline genomes of children with cancer holds the promise to augment diagnosis, treatment, and screening, and to permit the exploration of early initiation of cancer prevention strategies of patients with high risk of cancer. Citation Format: Vivian Chang, Hane Lee, Tom Davidson, Naghmeh Dorrani, Erin O'Leary, Patricia A. Ganz, Stanley F. Nelson, Julian A. Martinez-Agosto. Clinical exome sequencing in the diagnosis of pediatric cancer predisposition. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Susceptibility and Cancer Susceptibility Syndromes; Jan 29-Feb 1, 2014; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(23 Suppl):Abstract nr 08. doi:10.1158/1538-7445.CANSUSC14-08

Anesthetic management of comprehensive dental restoration in a child with glutaric aciduria type 1 using volatile sevoflurane

Glutaric aciduria type 1 (GA1) is a rare, inherited mitochondrial disorder that results from deficiency of mitochondrial glutaryl-CoA dehydrogenase. Most patients develop neurological dysfunction early in life, which leads to severe disabilities. We present a 37-month-old girl with GA1 manifested as macrocephaly and hypotonia who received comprehensive dental restoration surgery under general anesthesia with sevoflurane. She was placed on specialized fluid management during a preoperative fasting period and anesthesia was administered without complications. All the physiological parameters, including glucose and lactate blood levels and arterial blood gas were carefully monitored and maintained within normal range perioperatively. Strategies for anesthetic management should include prevention of pulmonary aspiration, dehydration, hyperthermia and catabolic state, adequate analgesia to minimize surgical stress, and avoidance of prolonged neuromuscular blockade. We administered general anesthesia with sevoflurane uneventfully, which was well tolerated by our patient with GA1. Additionally, communication with a pediatric geneticist and surgeons should be undertaken to formulate a comprehensive anesthetic strategy in these patients.

New technologies pave way for fetal personalized medicine

New technologies pave way for fetal personalized medicine

Geneticist to head NICHD

Geneticist to head NICHD

Cleft Palate

Cleft Palate

BEGIN Partnership: Using Problem-Based Learning To Teach Genetics & Bioethics

A science education center at a university medical school had grant funding to develop a genetics curriculum unit but needed a dissemination plan. A statewide science teacher organization that provided professional development training was facing decreased funding. These two groups combined their efforts, and created a unique partnership, called BEGIN (Biotechnology, Ethics and Genetics Instructional Network) that has brought together university medical and science faculty and high school biology teachers. The main goal of this partnership is to provide high school biology teachers with new instructional tools to face the challenges of teaching genetics and bioethics in a manner that is content-rich, research and standards-based, and relevant to students' lives. This article describes the BEGIN partnership and summarizes the tiered approach used for designing, pilot-testing, and disseminating a new problem-based learning (PBL) curriculum module on the bioethics of DNA testing for Huntington's disease. The article also provides some preliminary data on the effectiveness of this approach in transforming teacher practice. BEGIN: A Unique Partnership Between University Faculty & Science Teachers BEGIN was launched in 2003 using grant funding from the National Institutes of Health's National Human Genome Research Institute (NHGRI). This collaborative partnership brings together faculty and staff of the Life Sciences Learning Center (a hands-on science education laboratory located at the University of Rochester School of Medicine and Dentistry) and science educators from the New York State Biology-Chemistry Professional Development Network. The goal of this project is to develop and disseminate PBL-based activities that introduce high school students to the ethical, legal, and social implications (ELSI) of genetic testing. BEGIN focuses on curriculum and professional development, working primarily with high school teachers who teach biology courses based on the New York State Living Environment core curriculum (NYSED). In order to increase the likelihood that teachers will adopt new curricula and instructional practices, BEGIN uses an ongoing, multi-year process of curriculum development and professional development with teachers from the New York State Biology-Chemistry Professional Development Network. The process introduces PBL and other instructional strategies that are based on current educational research on effective, best practices. The centerpiece of the BEGIN partnership is a five-part PBL curriculum module called Family Secrets (Markowitz et al., 2006). This module engages students in constructing knowledge about DNA testing, Huntington's disease, and the bioethics of genetic testing. Using PBL strategies, students access and interpret relevant scientific information and data, collaborate with other students, and develop ownership of their solution to a real-life problem. These skills are all key characteristics of science inquiry, and correlate with the inquiry skills found in the National Science Education Standards (NRC, 1996). Family Secrets is the result of a three-year process of curriculum development, statewide pilot-testing, dissemination, and feedback. Family Secrets was created by a Development Team of master teachers from the New York State BiologyChemistry Professional Development Network, and scientists, a pediatric geneticist, and a bioethicist from the University of Rochester. A group of ten biology Pilot Mentors from throughout New York State pilot-tested the initial version of Family Secrets in their classrooms, and provided year-long feedback to the Development Team. A revised version of Family Secrets was then introduced to 62 statewide Biology Mentors at a four-day summer institute at the University of Rochester Medical Center. Mentors field-tested the revised curriculum, and provided the Development Team with preliminary evaluation data to assess the impact of Family Secrets and the PBL process on classroom instruction and student learning. …

A Surprising Postnatal Diagnosis

CASE: A1-week-oldinfantwasreferredtothe pediatric genetics clinic for evaluationof hypotonia and dysmorphic facial fea-tures. She was accompanied by her 37-year-old mother and 52-year-old father.The infant was her parents’ first child. Sheweighed 2,600 g at birth and was deliv-ered after a full-term uncomplicated preg-nancy. According to the mother, at 18weeks of gestation, a quadruple screenwas performed, which was interpreted as“within normal limits.” At the time, themother stated that she reviewed her resultswith her obstetrician and felt reassured,decidingagainstundergoinganamniocen-tesis. “He told me ‘The results came backfine, so there is no need to worry,’” sheexplained. A routine ultrasound examina-tion at 20 weeks revealed no apparentabnormalities.Thedeliverywasunremark-able. In the newborn period, the pediatri-ciannotedhypotoniaanddysmorphicfea-tures, but the baby was otherwise healthyand was discharged home after 2 days.Onphysicalexamination,atthetimeofthe visit, the infant had the typical physicalfeatures of Down syndrome: brachyceph-aly; midface hypoplasia with bilateral epi-canthal folds, and upslanting obliquity ofthe palpebral fissures. No heart murmurwas auscultated. On neurological exami-nation, the infant was diffusely hypotonicwith poor head control.The history of poor feeding, diffuse hy-potonia, and the distinct facial appearanceraised our concerns that the infant hadDown syndrome. A karyotype confirmedthe diagnosis of trisomy 21 (Fig. 1). Theechocardiogram was normal, with no evi-dence of an endocardial cushion defect orother heart abnormality in keeping withthe normal targeted prenatal sonogram.The pediatric geneticist discussed theclinicalimpressionwiththemother,whoexpressed complete shock. She said thather provider had called her “normal”quad screen reassuring, and after theirdiscussion, she felt confident in her de-cision to decline amniocentesis. Whywas the diagnosis of Down syndromemissed?

Differential Detection of Deletion 22q11.2 Syndrome by Specialty and Indication

This study identified cytogenetic abnormalities in a population screened for deletion 22q11.2 syndrome (D22S) by fluorescence in situ hybridization (FISH) and G-banding and correlated these abnormalities to referring specialty and submitted indications. Requests for the D22S FISH assay were retrospectively reviewed over a 29-month period in our institution. Positive test results for D22S FISH and other abnormalities found by other FISH assays and G-banding were correlated to submitting specialist and indication. Thirteen medical services ordered D22S FISH testing on 297 patients over 29 months. The detection rate for all cytogenetic aberrations was 9.4% (28 of 297) including 5.4% (16 of 297) for D22S detection by FISH and 2.7% (8 of 297) for detection of additional cytogenetic anomalies by G-banding cytogenetics. Sixty-six of 297 patients negative by D22S FISH and G-banding were screened using other FISH assays and 3 of 47 (6.4%) patients screened using subtelomeric probes were positive for deletion and 1 of 3 (33%) patients screened for Prader-Willi syndrome was positive for deletion. Pediatric geneticists requested 53.9% (160 of 297) of the tests, yielding 60.7% (17 of 28) of positive test results. Tetralogy of Fallot and developmental delay were the indications associated with the most positive test results. In our institution, pediatric geneticists identify the largest spectrum of indications with D22S and appear most aware of the association of developmental delay with D22S. Performing conventional cytogenetics and other FISH assays, in addition to FISH for D22S, is important because there is considerable overlap between D22S and the phenotype of several other syndromes.