BackgroundThere are limited reports of the use of whole exome sequencing (WES) as a clinical diagnostic tool. Moreover, there are no reports addressing the cost burden associated with genetic tests performed prior to WES.ObjectiveWe demonstrate the performance characteristics of WES in a pediatric setting by describing our patient cohort, calculating the diagnostic yield, and detailing the patients for whom clinical management was altered. Moreover, we examined the potential cost-effectiveness of WES by examining the cost burden of diagnostic workups.MethodsTo determine the clinical utility of our hospital’s clinical WES, we performed a retrospective review of the first 40 cases. We utilized dual bioinformatics analyses pipelines based on commercially available software and in-house tools.ResultsOf the first 40 clinical cases, we identified genetic defects in 12 (30%) patients, of which 47% of the mutations were previously unreported in the literature. Among the 12 patients with positive findings, seven have autosomal dominant disease and five have autosomal recessive disease. Ninety percent of the cohort opted to receive secondary findings and of those, secondary medical actionable results were returned in three cases. Among these positive cases, there are a number of novel mutations that are being reported here. The diagnostic workup included a significant number of genetic tests with microarray and single-gene sequencing being the most popular tests. Significantly, genetic diagnosis from WES led to altered patient medical management in positive cases.ConclusionWe demonstrate the clinical utility of WES by establishing the clinical diagnostic rate and its impact on medical management in a large pediatric center. The cost-effectiveness of WES was demonstrated by ending the diagnostic odyssey in positive cases. Also, in some cases it may be most cost-effective to directly perform WES. WES provides a unique glimpse into the complexity of genetic disorders.

We report on 19 individuals with a recurrent de novo c.607C>T mutation in PACS1. This specific mutation gives rise to a recognizable intellectual disability syndrome. There is a distinctive facial appearance (19/19), characterized by full and arched eyebrows, hypertelorism with downslanting palpebral fissures, long eye lashes, ptosis, low set and simple ears, bulbous nasal tip, wide mouth with downturned corners and a thin upper lip with an unusual “wavy” profile, flat philtrum, and diastema of the teeth. Intellectual disability, ranging from mild to moderate, was present in all. Hypotonia is common in infancy (8/19). Seizures are frequent (12/19) and respond well to anticonvulsive medication. Structural malformations are common, including heart (10/19), brain (12/16), eye (10/19), kidney (3/19), and cryptorchidism (6/12 males). Feeding dysfunction is presenting in infancy with failure to thrive (5/19), gastroesophageal reflux (6/19), and gastrostomy tube placement (4/19). There is persistence of oral motor dysfunction. We provide suggestions for clinical work‐up and management and hope that the present study will facilitate clinical recognition of further cases. © 2016 Wiley Periodicals, Inc.

Supervision is critical to the training of genetic counselors. Limited research exists on the influence of supervision training and experience on the development of genetic counseling supervisors. The purpose of this study was to investigate the impact of supervision training in addition to supervisory and clinical experience on supervisory identity development, and the perceived confidence and competence supervisors have in their own supervisory skills. In addition, we explored genetic counselors' (N = 291) interest in and barriers to training as well as perspectives on requirements for supervisors. Results indicated clinical experience, supervision experience, and formal supervision training are positively associated with genetic counselors' supervisory identity development as measured by the Psychotherapy Supervisory Development Scale (PSDS) (p < 0.05). Despite a moderate correlation between supervision experience and formal training (ρ = 0.42, p < 0.001), both had independent effects on PSDS scores (p < 0.04). A majority of genetic counselors were interested in receiving supervision training but noted lack of available training as a barrier. The majority of participants indicated that supervisors should be certified as genetic counselors, but there was no consensus on training requirements. Development of additional supervision training opportunities for genetic counselors should be considered.

This study evaluated the use of the Curaçao criteria for the diagnosis of HHT in the pediatric population with a family history of HHT. In those between the age of 0 and 21 years who meet 1 criterion (unlikely HHT) or 2 criteria (possible HHT), genetic testing is preferred for diagnosis. The Curaçao criteria appear to reliably diagnose HHT in children and adolescents who meet 3 or 4 criteria (definite HHT).

This study describes the development of a self-efficacy scale that is specific to genetic counseling and based both on Bandura's self-efficacy theory (2006) and the Accreditation Council for Genetic Counseling practice-based competencies (2013). The phase 1 validation compared genetic counseling students (n = 20) and genetic counselors (n = 18). Nine items were removed from the scale at this point for lack of discrimination or redundancy. The phase 2 validation included a larger cohort of genetic counseling students (n = 168). Factor analysis identified six factors accounting for 58% of the total variance. Cronbach's alpha as well as the inter-item correlations and item-total correlations of both the full scale items and underlying factors indicated that the items and factors of the scale are sufficiently related, but not redundant. The newly developed Genetic Counseling Self-Efficacy Scale (GCSES) has the potential to be used as an outcome measure in research related to training or professional development of genetic counselors as well as for a training tool.

The purpose of this study was to determine if a genetic counseling student's perception of the supervisory working alliance (SWA) is related to their self-efficacy on select clinical practice-based competencies (PBCs), evaluating the second tenet of the Reciprocal Engagement Model of Supervision (REM-S) from a student perspective. Second year genetic counseling students (N = 168) completed a survey containing demographic and clinical rotation experience questions, the Supervisory Working Alliance Inventory-Trainee Form (SWAI-T), and the Genetic Counseling Self-Efficacy Scale (GCSES). Overall, the SWAI-T was significantly associated with all factors of the GCSES. Additionally, the relationship between the SWAI-T and self-efficacy was specific to those who had only one supervisor, thus highlighting the SWA may be most important under these circumstances. This serves as an important step in being able to guide supervisors toward effective methods in supervision, which may include encouraging supervisors to build a strong relationship with their supervisee in order to help strengthen the student's confidence in their clinical skills.

Biallelic HPGD mutations are found in the majority of patients with typical PHO, and sequencing of the HPGD gene is a highly specific first-line investigation for patients presenting in this way, particularly during childhood. The c.175_176delCT frameshift mutation appears to be recurrent and to be the commonest HPGD mutation in Caucasian families.

Hereditary hemorrhagic telangiectasia (HHT), the second most common inherited bleeding disorder, is associated with the development of malformed blood vessels. Abnormal blood vessels may be small and cutaneous or mucosal (telangiectasia), with frequent complications of bleeding, or large and visceral (arteriovenous malformations [AVMs]), with additional risks that can lead to significant morbidity and even mortality. HHT can present in many different ways and can be difficult to recognize, particularly in younger patients in the absence of a known family history of disease or epistaxis, its most common manifestation. HHT is commonly diagnosed using the established Curaçao clinical criteria, which include (1) family history, (2) recurrent epistaxis, (3) telangiectasia, and (4) visceral AVMs. Fulfillment of 3 or more criteria provides a definite diagnosis of HHT, whereas 2 criteria constitute a possible diagnosis of HHT. However, these criteria are insufficient in children to rule out disease due to the age-dependent development of some of these criteria. Genetic testing, when positive, can provide definitive diagnosis of HHT in all age groups. Clinical course is often complicated by significant epistaxis and/or gastrointestinal bleeding, leading to anemia in half of adult patients with HHT. The management paradigm has recently shifted from surgical approaches to medical treatments aimed at control of chronic bleeding, such as antifibrinolytic and antiangiogenic agents, combined with aggressive iron replacement with intravenous iron. Guidelines for management of HHT, including screening and treatment, were determined by expert consensus and originally published in 2009 with updates and new guidelines in 2020.