Pediatric Genetics Clinic Research Articles

A family-based approach to cascade genetic testing in a pediatric cancer genetics clinic.

Hereditary cancer predisposition disorders account for up to 10% of all pediatric cancers. Genetic counseling for families of the proband includes risk assessment and recommendations for cascade genetic testing for parents and siblings, but there is no standardized method for cascade testing in place resulting in variability in how clinics approach cascade genetic testing. We explored the uptake and outcomes associated with a family-based approach to cascade testing, for non-syndromic cancer predisposition disorders, at a pediatric cancer genetics clinic serving an ethnically diverse patient population. A retrospective chart review was conducted to evaluate test uptake in the parents and siblings of 106 pediatric probands. The study included 99 mothers, 97 fathers, 116 full siblings, and 53 half siblings who were recommended testing due to genetic risk. Of these relatives, 156 (43%) had documentation of completed cascade testing within twenty-four months after the proband's result disclosure. Completion of cascade testing varied by the type of family member and degree of relatedness. 41% of mothers (41/99) were tested in comparison to 26% of fathers (26/97) and 70.6% of full siblings (82/116) were tested compared to 13.2% of half siblings (7/53). Statistical analysis using chi-squared tests revealed that siblings were more likely to have completed testing than parents (p < 0.001). Furthermore, amongst parents, mothers were more likely to complete testing than fathers (p = 0.03) and amongst siblings, full siblings were more likely to complete testing than half siblings (< 0.001). The proband's age (p = 0.008), parents' preferred language (p = 0.002), and interpreter use during visit (p = 0.004) were the factors associated with differences in test uptake amongst siblings, whereas the proband's race/ethnicity (p = 0.019) was the only factor associated with differences in test uptake amongst parents. The most common barriers noted in charts for lack of test completion included country of residence, lack of insurance, and loss to follow-up. In conclusion, we found that test uptake differed significantly among relatives of a proband with siblings being more likely to test than parents. We also found differences in the demographic and clinical factors associated with test uptake in parents and siblings. Future studies need to validate these differences and further explore the underlying cause of variation in test uptake among relatives.

Single-Center Experience in Establishing a Pediatric Kidney Genetics Clinic

Single-Center Experience in Establishing a Pediatric Kidney Genetics Clinic

Diagnostic findings and yield of investigations for children with developmental regression.

Childhood conditions that feature developmental regression are poorly understood. Phenotype-genotype characterization and diagnostic yield data are needed to inform clinical decision-making. The aim of this study was to report the conditions featuring developmental regression and assess diagnostic yields of investigations. A retrospective chart review of children presenting with developmental regression to a tertiary pediatric genetic clinic between 2018 and 2021 was performed. Of 99 children, 30% (n = 30) had intellectual disability (ID), 21% (n = 21) were autistic, 39% (n = 39) were autistic with ID, and 9% (n = 9) did not have ID or autism. Thirty-two percent (n = 32) of children received a new diagnosis, including eight molecular findings not previously reported to feature developmental regression. Of the children investigated, exome sequencing (ES) provided the highest diagnostic yield (51.1%, n = 24/47), highest (63.6%, n = 14/22) for children with ID, 50% for autistic children with ID (n = 6/12) and children without autism or ID (n = 3/6), and 14.3% (n = 1/7) for autistic children without ID. We highlight the conditions that feature developmental regression and report on novel phenotypic expansions. The high diagnostic yield of ES, regardless of autism or ID diagnosis, indicates the presence of developmental regression as an opportunity to identify the cause, including for genetic differences not previously reported to include regression.

Cardiac affection in lysosomal storage disorders and effect of enzyme replacement therapy

Background Cardiac dysfunction is a serious problem in the majority of lysosomal storage diseases (LSDs), emerges silently, and contributes significantly to early mortality. Aim To detect the cardiac affection of LSDs and to evaluate the effectiveness of enzyme replacement therapy. Patients and methods This cross-sectional study was conducted on 30 children with a confirmed diagnosis of LSDs, who were under enzyme replacement therapy at the Pediatric Metabolic and Genetic Clinic of Zagazig University Children Hospital during the period of 6 months from June 2022 to December 2022. An echocardiographic examination was conductede for all patients before and after treatment. Results Ejection fraction (EF) was significantly increased after treatment than before treatment (P value &lt;0.001). In the MPS IV (Morquio) group, valvular lesions, ventricular hypertrophy, and pulmonary pressure were insignificantly different between the studied children before and after treatment. Conclusion Ejection fraction in the MPS IV (Morquio) group was significantly improved after treatment than before treatment.

Lessons Learned from the Point-of-Care Use of a Facial Analysis Technology

Purpose: We aimed to evaluate the utility of facial analysis technology for genetic diagnoses in a typical pediatric genetic clinic. Methods: A retrospective review identified children (aged &lt;18 years) who had not previously received a definitive genetic diagnosis and underwent a comprehensive genetic evaluation. Their photographs and relevant clinical non-facial features were uploaded to the CLINIC application of the Face2Gene web interface, and the resulting analysis was accessed and correlated to the molecular diagnosis. Results: Of the 23 children included, the overall diagnostic yield in this study was 60.9% (14/23). In total, 64.3% of patients had the correct condition suggested in the top 10 differential diagnoses. The gestalt similarity was only 55.6%, but the phenotypic features added by the clinician showed a similarity of more than the medium level in all patients. Conclusion: Our data underscore the usefulness of facial analysis technology as an auxiliary point-of-care tool in pediatric genetic clinics, and we also present some considerations to increase accuracy.

Spectrum of congenital and inherited ocular disorders seen in a genetic clinic: Experience of a developing ocular genetic service.

Hereditary causes are an important etiological category of childhood blindness. This study reports the real-world experience of a developing ocular genetic service. The study was carried out from Jan 2020 to Dec 2021 jointly by the Pediatric Genetic Clinic and the Department of Ophthalmology of a tertiary care hospital in North-West India. Children presenting to the genetic clinic with congenital or late-onset ocular disorder(s) and any individual (irrespective of age) suffering from an ophthalmic disorder and referred by an ophthalmologist for genetic counseling for himself/herself and/or his/her family member(s) were included. Genetic testing (exome sequencing/panel-based sequencing/chromosomal microarray) was outsourced to third-party laboratories with the cost of the test being borne by the patient. Exactly 8.6% of the registered patients in the genetic clinic had ocular disorders. Maximum number of patients belonged to the category of anterior segment dysgenesis, followed by microphthalmia anophthalmia coloboma spectrum, lens disorders, and inherited retinal disorders in decreasing numbers. The ratio of syndromic ocular to isolated ocular disorders seen was 1.8:1. Genetic testing was accepted by 55.5% of families. The genetic testing was clinically useful for ~35% of the tested cohort, with the opportunity for prenatal diagnosis being the most useful application of genetic testing. Syndromic ocular disorders are seen at a higher frequency compared to isolated ocular disorders in a genetic clinic. Opportunity for prenatal diagnosis is the most useful application of genetic testing in ocular disorders.

Access to clinically indicated genetic tests for pediatric patients with Medicaid: Evidence from outpatient genetics clinics in Texas

Little is known about how Medicaid coverage policies affect access to genetic tests for pediatric patients. Building upon and extending a previous analysis of prior authorization requests (PARs), we describe expected coverage of genetic tests submitted to Texas Medicaid and the PAR and diagnostic outcomes of those tests. We retrospectively reviewed genetic tests ordered at 3 pediatric outpatient genetics clinics in Texas. We compared Current Procedural Terminology (CPT) codes with the Texas Medicaid fee-for-service schedule (FFSS) to determine whether tests were expected to be covered by Medicaid. We assessed completion and diagnostic yield of commonly ordered tests. Among the 3388 total tests submitted to Texas Medicaid, 68.9% (n= 2336) used at least 1 CPT code that was not on the FFSS and 80.7% (n= 2735) received a favorable PAR outcome. Of the tests with a CPT code not on the FFSS, 60.0% (n= 1400) received a favorable PAR outcome and were completed and 20.5% (n= 287) were diagnostic. The diagnostic yield of all tests with a favorable PAR outcome that were completed was 18.7% (n= 380/2029). Most PARs submitted to Texas Medicaid used a CPT code for which reimbursement from Texas Medicaid was not guaranteed. The frequency with which clinically indicated genetic tests were not listed on the Texas Medicaid FFSS suggests misalignment between genetic testing needs and coverage policies. Our findings can inform updates to Medicaid policies to reduce coverage uncertainty and expand access to genetic tests with high diagnostic utility.

Clinical Characteristics of Children with Neurodevelopmental Delay and Pathogenic Copy Number Variations in Chromosomal Microarray Analysis

Objective: In this study, we report the clinical characteristics of a small cohort of children with neurodevelopmental delay and pathogenic copy number variations (CNV) in chromosomal microarray. Materials and Methods: We retrospectively analyzed children aged 0-18 years with neurodevelopmental delay and a pathogenic CNV in the chromosomal microarray analysis, who had been evaluated in the pediatric genetics and pediatric neurology outpatient clinics of a tertiary hospital between August 2017 and March 2021. Results: Twenty-four patients were included, 15 (62.5%) of them were girls. The mean age at diagnosis was 47.0±42.0 months (age range: 4-133 months). Most of the children (n=17, 70.8%) were diagnosed with welldefined microdeletion/microduplication syndromes. Of 28 CNVs in 24 patients; 21 (75%) were deletions, 7 (25%) were duplications. Fifteen (62.5%) of them had GDD, seven (29.2%) had ID, and three (12.5%) had ASD. A history of preterm birth and small birth weight for gestational age were present in four and five children, respectively. Neuroimaging was compatible with hypoxic-ischemic injury in two children and hypoglycemic sequel in one child. Facial dysmorphism was present in 19 (79.2%), hypotonicity in 14 (58.3%), epilepsy in eight (33.3%), microcephaly in seven (29.2%), macrocephaly in two (8.3%), hearing impairment in two (8.3%), and visual impairment in three (12.5%) children. Conclusion: Chromosomal microarray analysis is a valuable tool in patients with unexplained neurodevelopmental delay. Even in children with brain injury secondary to perinatal asphyxia and neonatal hypoglycemia, microarray analysis should be performed in cases with concomitant dysmorphism and/or multisystem involvement.

Genetic Basis of Childhood Cardiomyopathy.

The causes of cardiomyopathy in children are less well described than in adults. We evaluated the clinical diagnoses and genetic causes of childhood cardiomyopathy and outcomes of cascade genetic testing in family members. We recruited children from a pediatric cardiology service or genetic heart diseases clinic. We performed Sanger, gene panel, exome or genome sequencing and classified variants for pathogenicity using American College of Molecular Genetics and Genomics guidelines. Cardiomyopathy was diagnosed in 221 unrelated children aged ≤18 years. Children mostly had hypertrophic cardiomyopathy (n=98, 44%) or dilated cardiomyopathy (n=89, 40%). The highest genetic testing diagnostic yields were in restrictive cardiomyopathy (n=16, 80%) and hypertrophic cardiomyopathy (n=65, 66%), and lowest in dilated cardiomyopathy (n=26, 29%) and left ventricular noncompaction (n=3, 25%). Pathogenic variants were primarily found in genes encoding sarcomere proteins, with TNNT2 and TNNI3 variants associated with more severe clinical outcomes. Ten children (4.5%) had multiple pathogenic variants. Genetic test results prompted review of clinical diagnosis in 14 families with syndromic, mitochondrial or metabolic gene variants. Cascade genetic testing in 127 families confirmed 24 de novo variants, recessive inheritance in 8 families, and supported reclassification of 12 variants. Genetic testing of children with cardiomyopathy supports a precise clinical diagnosis, which may inform prognosis.

Clinical, demographic and genetic features of patients with congenital heart disease : A single center experience

Objective: We aimed to evaluate the demographic and clinical characteristics of children with congenital heart disease (CHD) in a private pediatric cardiovascular genetics clinic in Istanbul from January 2016 to July 2018 and increase the awareness and emphasize the importance of genetic counseling in CHD. Patients and Methods: One hundred and seventeen patients (50 female, 67 male) from 3 days of age to 25 years of age in 17 months period ( January 2016 to July 2018) were retrospectively analyzed. Data included age, sex, echocardiography results, extracardiac features, genetic test results, consanguinity and any family member with heart disease. Pearson’s chi-squared test with 1 degree of freedom and 5% significance was used for correlations. Results: Consanguinity rate was 23.9%. Most common diagnosis was Tetralogy of Fallot (TOF) followed by atrial septal defect (ASD) and ventricular septal defect (VSD) equally. 30 patients had genetic testing which revealed a diagnosis in 36.6 % of the patients. 6 patients had DiGeorge, one had Renpenning,one had Kabuki syndrome. We had one NODAL, one MYH7 and one MYH6 variant. Conclusion: Genetic testing in CHD has a high diagnostic yield. Genetic counseling can help diagnostic, prognostic, and therapeutic and family planning decision making.

EP297: Overview of pediatric genetic counseling clinic models and genetic counselors' perceptions of them

eP297: Overview of pediatric genetic counseling clinic models and genetic counselors' perceptions of them

EP517: Differences in genetic testing uptake in a large metropolitan pediatric outpatient genetics clinic over time

Genetic testing is an important diagnostic tool in pediatric genetics that can end a diagnostic odyssey and help a patient receive prompt and appropriate medical care. Historically, prior authorizations and approvals for genetic tests often occurred and were initiated by the clinic directly and testing could only be completed on peripheral blood samples. It often took several weeks to months to obtain prior authorization. This introduced barriers to completing the recommended testing. More recently, commercial genetic testing laboratories work directly with payers to obtain prior authorizations for genetic tests rather than the clinic. In addition, buccal swabs and saliva samples are widely utilized and accepted as an alternative, non-invasive sample type for a majority of genetic tests. This has allowed our genetics clinic at Texas Children's Hospital (TCH) to send genetic tests for patients during the clinical encounter or shortly after. In the context of updates to commercial laboratory billing and specimen type updates, we sought to describe genetic tests completed and compare the difference in uptake of genetic testing in our outpatient genetics clinic between 2018 and 2021. We completed a retrospective review of all genetic tests recommended for pediatric patients seen in the outpatient Genetics Clinic at TCH from March 1, 2021 through August 31, 2021. All patients had private or public insurance accepted in Texas or the United States. Data was compared to similar, previously collected genetic testing data in the same period in 2018 at TCH including type of payer, genetic tests recommended, and outcomes of completed genetic tests. In 2018, 1,173 unique tests were recommended; 702 (59.8%) tests were sent on patients with a public payer and 471 (40.2%) tests had private payers. All tests had prior authorizations completed by the institution and required a peripheral blood sample. The 2021 data included 903 unique recommended genetic tests of which 403 (44.6%) of the tests were sent on patients who had a private payer and 500 (55.4%) had a public payer. Buccal samples were collected during the clinical encounter for 293/903 (32.4%) tests. Of those, four tests were not completed and eight tests were sponsored and not billed to a payer. The remaining 281 tests were billed directly to the performing genetic testing laboratory. Tests billed to public payers were more likely (p<0.0001) to have been completed in 2021 compared to 2018. Tests billed to private payers were not more likely to be completed in the same period (p=0.83). In 2021, 791 (87.6%) of the recommended tests were billed directly to the performing commercial laboratory. Of those, 645 (81.5%) were completed. In 2018, when prior authorizations were obtained by the institution, 665 (57.6%) were completed (p<0.0001). Genetic testing uptake has improved in our pediatric outpatient genetics clinic between 2018 and 2021. Increased uptake in genetic testing can shorten the diagnostic odyssey for pediatric patients and help them more quickly and efficiently access necessary medical care. The improved uptake in genetic testing in our clinic may be attributed to recent updates to billing practices and the use of alternative sample types accepted at commercial genetic testing laboratories. Some genetic tests can now be completed the same day as the clinical encounter or at home with buccal swabs. This reduces the potential barriers patients may face related to limited transportation, availability during business hours, financial constraints, and invasive testing. Additional investigation into alternative billing practices and how it impacts genetic testing and patient satisfaction should be completed.

Abstract- Poster

BACKGROUND:Sanfilippo syndrome, one of mucopolysaccharidoses is neuro developmental disorder characterised by severe degeneration of the central nervous system, resulting in mental retardation and hyperactivity, typically commencing during childhood. Visual changes, difficulty in breathing and swallowing, respiratory infections, heart disease, enlarged liver and spleen, hernias are also present along with musculoskeletal abnormalities of spine, hip and knee limiting the overall life expectancy to late teens or early twenties. Multi system involvement in neurodevelopmental disorders like Sanfilippo syndrome demands a multi modal approach.CASE REPORT:A 7-year-old, girl, studying kindergarten, coming from a middle socio-economic status, living in a nuclear family set-up was diagnosed with Sanfillipo syndrome with co-morbid ADHD and moderate intellectual disability. Born to third degree consanguineous parents her ante-natal, natal and immediate post-natal period was uneventful. In 2019 she presented to us referred from our Paediatric orthopaedic department with incidental finding for mucopolysaccharidoses. She presented to us with complaints of hyperactivity and poor scholastic performance. She was initially seen in our Child health Clinic and later was evaluated and diagnosed as Sanfilippo syndrome is one of mucopolysaccharidoses in Pediatric neurology and Medical genetics clinic. After assessment of for the concerns of referral under ACTeRS she was diagnosed with co-morbid ADHD. She was treated with low dose anti-psychotic and had no response. Hence as a multi-modal treatment approach for her co-morbid ADHD with Sanfillipo syndrome - she was started on T.Atomoxetine and had 3 months training program for NDD in our Nambikkai Nilayam (NN) with surgical corrections for skeletal deformities in our Pediatric ortho department prior to her admission in NN. With these multi -modality measures she improved in her symptoms overall.CONCLUSION:With increasing awareness and health care facility there has been an outburst in incidence of neuro developmental and genetic disorders. Though a number of genetic and biochemical diagnostic methods have been developed to confirm the diagnosis, there is no effective therapy available for neuro developmental and genetic disorders – in this patient it was MPS III. Multi system involvement demanding multi-disciplinary approach – involving multiple specialities is needed to improve the quality of life in these children and to reduce the care giver burden.

Evaluating the clinical utility of early exome sequencing in diverse pediatric outpatient populations in the North Carolina Clinical Genomic Evaluation of Next-generation Exome Sequencing (NCGENES) 2 study: a randomized controlled trial

BackgroundExome sequencing (ES) has probable utility for shortening the diagnostic odyssey of children with suspected genetic disorders. This report describes the design and methods of a study evaluating the potential of ES as a routine clinical tool for pediatric patients who have suspected genetic conditions and who are in the early stages of the diagnostic odyssey.MethodsThe North Carolina Clinical Genomic Evaluation by Next-generation Exome Sequencing (NCGENES) 2 study is an interdisciplinary, multi-site Phase III randomized controlled trial of two interventions: educational pre-visit preparation (PVP) and offer of first-line ES. In this full-factorial design, parent-child dyads are randomly assigned to one of four study arms (PVP + usual care, ES + usual care, PVP + ES + usual care, or usual care alone) in equal proportions. Participants are recruited from Pediatric Genetics or Neurology outpatient clinics in three North Carolina healthcare facilities. Eligible pediatric participants are < 16 years old and have a first visit to a participating clinic, a suspected genetic condition, and an eligible parent/guardian to attend the clinic visit and complete study measures. The study oversamples participants from underserved and under-represented populations. Participants assigned to the PVP arms receive an educational booklet and question prompt list before clinical interactions. Randomization to offer of first-line ES is revealed after a child’s clinic visit. Parents complete measures at baseline, pre-clinic, post-clinic, and two follow-up timepoints. Study clinicians provide phenotypic data and complete measures after the clinic visit and after returning results. Reportable study-related research ES results are confirmed in a CLIA-certified clinical laboratory. Results are disclosed to the parent by the clinical team. A community consultation team contributed to the development of study materials and study implementation methods and remains engaged in the project.DiscussionNCGENES 2 will contribute valuable knowledge concerning technical, clinical, psychosocial, and health economic issues associated with using early diagnostic ES to shorten the diagnostic odyssey of pediatric patients with likely genetic conditions. Results will inform efforts to engage diverse populations in genomic medicine research and generate evidence that can inform policy, practice, and future research related to the utility of first-line diagnostic ES in health care.Trial registrationClinicalTrials.govNCT03548779. Registered on June 07, 2018.

Outcomes of prior authorization requests for genetic testing in outpatient pediatric genetics clinics

PurposeGenetic testing is an important diagnostic tool in pediatric genetics clinics, yet many patients face barriers to testing. We describe the outcomes of prior authorization requests (PARs) for genetic tests, one indicator of patient access to clinically recommended testing, in pediatric genetics clinics. MethodsWe retrospectively reviewed PARs for genetic tests (n = 4,535) recommended for patients <18 years of age (n = 2,798) by pediatric medical geneticists at two children’s hospitals in Texas, 2017–2018. We described PAR outcomes, accompanying diagnostic codes, and diagnostic yield. ResultsThe majority (79.9%) of PARs received a favorable outcome. PARs submitted to public payers were more likely to receive a favorable outcome compared with private payers (85.5% vs. 70.3%, respectively; p < 0.001). No diagnostic codes were associated with higher likelihood of PAR approval for exome sequencing. Among the 2,685 tests approved and completed, 522 (19.4%) resulted in a diagnosis. ConclusionThough there was a high PAR approval rate, our findings suggest that insurance coverage remains one barrier to genetic testing. When completed, genetic testing had a high yield in our sample. Further evidence of clinical utility and development of clinical practice guidelines may inform payer medical policy development and improve access to testing in the future.

Effectiveness of Promoting Mothers’ Caring Practices Regarding Their Down Syndrome Children on the Family Coping

Down Syndrome is a lifelong chromosomal disorder caused by an extra copy of chromosome number 21 inside each of the body’s cells. This genetic disorder, causes mental retardation and developmental delays. Aim of this study was to determine the effect of promoting mothers’ caring practices regarding their children with Down Syndrome on the family coping. Subjects and Method: A quasi-experimental research design used for sixty mothers and their children with Down Syndrome at Pediatric Outpatient Genetic Clinic of Tanta University Hospital. Three tools were used for data collection: Structured Interview Schedule to assess socio-demographic and mothers, knowledge about Down Syndrome, Mothers, Care Reporting Sheet and Family Crisis Oriented Personal Scales. Results: The total scores of knowledge for more than three quarters of mothers were low before educational program while, more than half of them had moderate level of knowledge and less than half of them had high level immediately after program. The total scores of most mothers, reported care were unsatisfactory before educational program while, the majority of them had satisfactory care immediately and one month after program. Family adaptation for nearly two thirds of caregivers was fair before program while, all of them had good adaptation immediately after program. Conclusion: There was a significant improvement of mothers, knowledge, reported care and family adaptation towards crises. Recommendations: Continuous health education program should be applied to mothers of children with Down Syndrome in health care facilities to improve their knowledge and practice that affect family adaptation.

Germline mutation in POLR2A: a heterogeneous, multi-systemic developmental disorder characterized by transcriptional dysregulation.

De novo germline variation in POLR2A was recently reported to associate with a neurodevelopmental disorder. We report twelve individuals harboring putatively pathogenic de novo or inherited variants in POLR2A, detail their phenotypes, and map all known variants to the domain structure of POLR2A and crystal structure of RNA polymerase II. Affected individuals were ascertained from a local data lake, pediatric genetics clinic, and an online community of families of affected individuals. These include six affected by de novo missense variants (including one previously reported individual), four clinical laboratory samples affected by missense variation with unknown inheritance—with yeast functional assays further supporting altered function—one affected by a de novo in-frame deletion, and one affected by a C-terminal frameshift variant inherited from a largely asymptomatic mother. Recurrently observed phenotypes include ataxia, joint hypermobility, short stature, skin abnormalities, congenital cardiac abnormalities, immune system abnormalities, hip dysplasia, and short Achilles tendons. We report a significantly higher occurrence of epilepsy (8/12, 66.7%) than previously reported (3/15, 20%) (p value = 0.014196; chi-square test) and a lower occurrence of hypotonia (8/12, 66.7%) than previously reported (14/15, 93.3%) (p value = 0.076309). POLR2A-related developmental disorders likely represent a spectrum of related, multi-systemic developmental disorders, driven by distinct mechanisms, converging at a single locus.

Crafting an Amish biomedical landscape

Within their pluralistic system of health care, the Amish make medical decisions influenced by cultural practice: a call for adherents to separate themselves from the outside world and to yield to the group. Using ethnographic research, this article discusses one aspect of the relationship between Amish communities near Lancaster, Pennsylvania, and a pediatric genetics clinic that has reformed the ways it mobilizes biomedicine in order to engage this community. Despite local Amish reticence to participate in biomedical systems, three elements discussed here are among those that help shape successful relationships between Amish families and the clinic: a carefully crafted physical space, a conceptualization of genetic medicine as skilled work, and a consideration for culturally appropriate use of time. Amish spaces of practice open to incorporate the clinic as biomedical spaces labor to incorporate Amish practice. The result is an emergent therapeutic landscape developing as a response to group social practice.

40 years and beyond for the National Society of Genetic Counselors: Reflections on genetic counseling practice.

The National Society of Genetic Counselors (NSGC) was established in 1979 and has grown from a small dedicated group of genetic counselors to over 5,000 certified genetic counselors in 2019. During this time period, there have been tremendous advances in the practice of genetic counseling, the availability of genetic testing, and the use of technology. These advances have significantly changed our roles and responsibilities and have contributed to the expansion and diversification of our field in clinical and non-clinical work settings. The launch of genetic counseling services in prenatal, pediatric, and adult genetics clinics has expanded to many medical specialties. Genetic counselors are also working in industry, public health, policy, education, research, and other work settings. With growth into new areas and the significant increase in the number of practitioners, genetic counselors have established themselves professionally and created opportunities where they can not only contribute to the delivery of quality genetic services, but lead the way. The counseling skills that are a core part of training as genetic counselors will continue to have broad application in diverse work settings and roles. Looking to the future, genetic counselors need to proactively consider tasks that artificial intelligence and other technologies can accomplish so that genetic counselors have the bandwidth to use their expertise to successfully and efficiently meet the growing demands for genetic counseling services. During the 40th anniversary celebration at the 2019 NSGC Annual Conference, three of NSGC's past presidents reflected on the early years of NSGC and clinical practice, recognized key accomplishments and where the profession stands today, and shared thoughts about the future of genetic counseling. Videos of the actual talks can be accessed by internet search 'NSGC Celebrates 40 Years' (https://www.nsgc.org/p/bl/et/blogid=53&blogaid=1162). A timeline of the genetic counseling profession is available at https://www.nsgc.org/page/nsgc-timeline.

Molecular genetics of phenylketonuria and tetrahydrobiopterin deficiency in Jordan.

BackgroundInformation regarding the prevalence of PKU in the Middle East in comparison to other world regions is scarce, which might be explained by difficulties in the implementation of national newborn screening programs.ObjectiveThis study seeks for the first time to genotype and biochemically characterize patients diagnosed with hyperphenylalaninemia (HPA) at the Pediatric Metabolic Genetics Clinic at the King Hussein Medical Center, Amman, Jordan.MethodsA total of 33 patients with HPA and 55 family members were investigated for pterins (neopterin and biopterin) and dihydropteridine reductase (DHPR) activity in dried blood spots. Patients with HPA were genotyped for phenylketonuria (PKU) and the genes involved in tetrahydrobiopterin (BH4) metabolism.ResultsIn total 20 patients were diagnosed with PKU due to phenylalanine hydroxylase (PAH) deficiency, 2 with GTP cyclohydrolase I (GTPCH) deficiency, 6 with DHPR deficiency, and 3 with the 6‐pyruvoyl‐tetrahydropterin synthase (PTPS) deficiency. Diagnosis was not possible in 2 patients. This study documents a high percentage of BH4 deficiencies within HPA patients. With one exception, all patients were homozygous for particular gene variants.ConclusionsThis approach enables differentiation between PKU and BH4 deficiencies and, thus, allows for critical selection of a specific treatment strategies.