Prevalence and Predictors of Hereditary Hemorrhagic Telangiectasia and Capillary-Malformation Arteriovenous Malformation Syndrome Among Children with Neurovascular Malformations.

OBJECTIVE: To investigate the prevalence and predictors of hereditary hemorrhagic telangiectasia (HHT) and capillary-malformation arteriovenous malformation (CM-AVM) syndrome among children with no prior personal or family history of these diseases who presented with an arteriovenous shunt lesion. STUDY DESIGN: A retrospective chart review was completed on patients aged 0 through 21 years with arteriovenous shunt lesions evaluated at our Cerebrovascular Center. Diagnosis of definite or suspected HHT or CM-AVM was based on clinical features and genetic testing. Associations between final diagnosis and type and number of lesions, epistaxis, telangiectasias, CM, and pulmonary AVMs were assessed. RESULTS: Eighty-nine patients were included. Thirteen (14.6%) had definite HHT, 11 (12.4%) suspected HHT, and 4 (4.5%) definite CM-AVM. Having ≥2 episodes of epistaxis/year and ≥ 2 sites with telangiectasias were each associated with definite HHT (P < .001). Having ≥ 2 CM was associated with definite CM-AVM (P < .001). Pulmonary AVM was associated with increased odds of having definite HHT (OR = 6.3, 95% CI: 1.2-33.4). Multiple lesions (OR = 24.5, 95% CI: 4.5-134.8) and arteriovenous fistulas (OR = 6.2, 95% CI: 1.9-20.3) each increased the likelihood of having definite HHT or CM-AVM. Genetic testing was positive in 31% of patients tested. CONCLUSIONS: We recommend that children with neurovascular shunt lesions be offered genetic testing and undergo further evaluation for HHT and CM-AVM. Awareness and early diagnosis of these conditions is a critical step toward improving long-term outcomes and preventing disease-associated complications.

Genetic counseling clinic model expansion: Impact on access for general genetics clinic.

Cincinnati Children's Hospital Medical Center (CCHMC) implemented a Genetic Counseling Clinic (GCC), where the appointment for a general genetics indication is conducted solely by a genetic counselor (GC). We conducted a retrospective chart review of 211 patient encounters scheduled in the GCC between January 1, 2022 and June 30, 2022 and collected patient demographics, wait time, appointment characteristics, referral indication, and clinical recommendations. To study impact on patient access, we compared patient demographics and appointment characteristics with 912 patient encounters scheduled in the General Genetics Clinic with a geneticist during the same time period. We found that there were not significant differences in patient demographics scheduled in the GCC as compared with the General Genetics Clinic with the exception of insurance type, where patients scheduled in the GCC were more likely to have private insurance. Patients scheduled in the GCC had a significantly shorter wait time, were more likely to complete their appointment, were more often new to the genetics division, and were more likely to be seen via telehealth (audio plus video or audio-only) as compared with patients scheduled in the General Genetics Clinic. The most common indications for patients scheduled in the GCC were post-test counseling (36.0%) followed by pre-test counseling and coordination of testing (22.3%), and first-line testing for autism, intellectual disability, and developmental delay (13.7%). Completed appointments in the GCC often resulted in the GC ordering genetic testing (67.5%). After genetic testing results were received, most patients (72.7%) did not require subsequent follow-up with the genetics division, thereby reducing burden to the medical genetics team. Our GCC increased access to genetic services and allowed GCs and clinical geneticists to better work at the top of their scope of practice.

Discussions of personal identity in genetic counseling supervision.

Fieldwork supervision is integral to genetic counseling students' training and has the potential to impact how included students feel in the genetic counseling field. For example, in related counseling fields, when supervisees and supervisors discuss their personal similarities or differences in ethnicity, supervisees report a stronger supervisory working alliance (SWA) (Journal of Multicultural Counseling and Development, 2001, 29, 102-113). However, the application of these studies on identity discussions to the genetic counseling field is currently unknown. The objective of this cross-sectional questionnaire-based study was to investigate (a) if genetic counseling students report having discussions of personal identity during fieldwork supervision, (b) who initiated any such discussions, (c) if there was a difference in the supervisory relationship between those who did and did not have discussions of personal identity, and (d) how students perceived the inclusivity of the genetic counseling profession and their genetic counseling programs. Discussions of personal identity were defined in this study as "discussions happening during supervision regarding how one or more aspects of personal identity impacts the provision of genetic counseling services and/or professional interactions" where personal identity included the student or supervisor's gender, sexual orientation, race, ethnicity, religion, disability status or other aspect of identity. Almost 40% of the participants (N = 190) reported discussing personal identity with their supervisor. For students identifying as white, discussions of personal identity were related to a stronger SWA (p = 0.014). However, for those with minoritized identities there was no relationship between the SWA and discussions of personal identity. Therefore, it is unclear from the current research whether discussions of personal identity can be an effective tool in improving inclusivity in the field of genetic counseling. Additional research is needed to explore the direct impact of identity discussions on the supervisory working alliance in genetic counseling supervision.

Creation and initial validation of a genetic counseling supervisory self-efficacy scale.

Fieldwork supervision is the "signature pedagogy" for training genetic counseling students, ensuring that students have the experience necessary to become minimally competent genetic counselors. According to the National Society of Genetic Counselors 2022 Professional Status Survey, roughly 40% of genetic counselors serve as supervisors for genetic counseling graduate students. Despite fieldwork supervision being essential for training, there are currently no validated supervision skill assessment tools for genetic counseling fieldwork supervisors to use for professional development. While a self-efficacy scale for genetic counselors currently exists, a comprehensive self-efficacy scale for genetic counseling supervision skills does not. The purpose of the study was to develop and validate a genetic counseling supervisory self-efficacy scale (GCSSES). This study was comparative, quantitative, and cross-sectional, with data collected via an online questionnaire which assessed supervision self-efficacy (95 items), derived from 154 published GC supervision competencies, demographics (5), experience (9), and supervisory development (18), using the Psychotherapy Supervisory Development Scale (PSDS). A total of 119 board-certified genetic counselors completed the survey. Factor analysis eliminated 40 items due to insufficient factor loading, and item-item correlation eliminated one item with elevated inter-item correlation, leaving 54 items on the finalized GCSSES. Exploratory factor analysis derived four GCSSES factors, which accounted for 65% of the variance in the scale: (a) Goal Setting, Feedback, and Evaluation; (b) Complex Aspects of Supervision; (c) Conflict Resolution; and (d) Working Alliance. Preliminary analyses show the GCSSES has high reliability and internal consistency (Cronbach's alpha = 0.99). Positive correlations between experience variables and supervisory self-efficacy were identified. A 54 item GCSSES was developed by this study. The GCSSES may serve as a tool for genetic counseling supervisors and graduate programs to assess skills, monitor professional development, and target training. A genetic counseling supervisory self-efficacy scale can also be used in future studies regarding training of genetic counseling supervisors.

Comparison of genetic testing documentation between genetic counselors and non-genetic counselors.

Implementation of genetic testing in healthcare increases, but access to, and number of, genetics providers remain scarce. This study analyzed the impact of genetic counselor (GC) involvement on frequency of documentation of pre- and post-test counseling of genetic testing between GCs and genetics providers (GPs), and GCs and non-genetics providers (NGPs). A retrospective chart review of 467 charts from patients who had genetic testing ordered between July 2016 and June 2018 at a primarily pediatric institution was conducted. GCs were involved for 223 charts (GC group), and not involved for 244 (non-GC group). The non-GC group was further stratified into patient charts with Genetics Providers (GP group) (n = 100) involved and those with Non-Genetics Providers (NGP group) (n = 144) involved. Categorical, binomial, pre-test variables (counseling, test description, results possibilities, insurance coverage, and cost) and categorical, binomial, post-test variables (results disclosure, family testing recommendations, recurrence risk, and provided resources) were collected and compared using Fisher's exact test (p < 0.005). With the exception of test description, documentation for all variables occurred more frequently in the GC group compared to the NGP group (all p < 0.001). Documentation for the majority of variables also occurred more frequently in the GC group compared to the GP group (p < 0.005), with the exceptions of overall pre-test counseling and family testing recommendations. GC involvement was associated with increased documentation of most pre- and post-test genetic counseling variables. With increased emphasis placed on transparency, accurateness, and access for patients of the EMR, in part due to the passage of the CARES Act, documentation should reflect the content of counseling provided. The cause of the documentation discrepancy identified may have differing effects on patient care and provider education.

How we approach genetics in the diagnosis and management of vascular anomalies.

Vascular anomalies are a heterogeneous group of disorders that are currently classified based on their clinical and histological characteristics. Over the past decade, there have been significant advances in molecular genetics that have led to identification of genetic alterations associated with vascular tumors, vascular malformations, and syndromes. Here, we describe known genetic alterations in vascular anomalies, discuss when and how to test, and examine how identification of causative genetic mutations provides for better management of these disorders through improved understanding of their pathogenesis and increasing use of targeted therapeutic agents in order to achieve better outcomes for our patients.

Impact of vascular anomalies on the PTEN phenotype in children and young adults.

Germline PTEN (phosphatase and tensin homolog) mutations lead to inappropriate cell survival and growth, and a predisposition to multiple cancers. Some patients also have vascular anomalies (VAs), and it is unclear whether these patients have different phenotypes or oncologic risks. We conducted a two-institution retrospective cohort study to better understand the phenotypes of children and young adults with PTEN mutations, and to compare individuals with VA to those without. Almost half of the patients had thyroid tumors and nearly one quarter developed gastrointestinal tumors before 30 years of age. The presence of VA was positively associated with bulky overgrowth but did not appear to modify oncologic risk.

Further validation of the Genetic Counseling Self-Efficacy Scale (GCSES): Its relationship with personality characteristics.

Demonstrating validity of a tool for genetic counseling self-efficacy could help determine if this is a useful tool for training outcomes or other purposes in the field. The purpose of the current study was to describe the relationship between genetic counseling self-efficacy, measured by scores on the Genetic Counseling Self-Efficacy Scale (GCSES), personality characteristics, clinical characteristics, and performance on the American Board of Genetic Counselors (ABGC) board certification examination. Genetic counselors, recruited via email through the National Society of Genetic Counselors (NSGC) Student Research Survey Program, completed an online questionnaire that included the GCSES, work locus of control (WLOC) scale, trait subscale of the State-Trait Anxiety Inventory (STAI), and questions related to board examination performance. Higher genetic counseling self-efficacy factor scores for four of six factors were significantly associated with lower WLOC scores indicative of internal locus of control (p's < .05); higher genetic counseling self-efficacy factor scores for all six factors were significantly associated with lower trait anxiety scores (p's < .05). In addition, increased years of experience and providing direct patient care were found to be significantly related to higher scores for all six-factor scores on the GCSES (p's ≤ .05). Multiple linear regression models were performed to assess combined effects of predictor and demographic variables and demonstrated that professional factors were most significantly associated with GCSES factor scores. Findings from the current study provide additional validation for the GCSES and add clarity to the relationships between genetic counseling self-efficacy, personality characteristics, and professional factors. Validation of the GCSES supports the usefulness of this tool as an outcome for genetic counseling training purposes. In addition, the GCSES could be used for self-reflective practice for genetic counselors. Further studies are needed to investigate the relationship between genetic counseling self-efficacy and genetic counselor competency.

Comparison of medical management and genetic counseling options pre- and post-whole exome sequencing for patients with positive and negative results.

Whole exome sequencing (WES) is expected to impact patient management, but data surrounding the types of downstream effects and how frequently these effects are observed depending on the type of WES results received is limited. This study investigated changes to medical management and genetic counseling (GC) options following WES for individuals with positive and negative results. Electronic medical records of patients who had positive (n = 37) or negative (n = 41) WES results from Cincinnati Children's Hospital were retrospectively reviewed. Pre- and post-WES management and GC options were analyzed as were differences between positive and negative results. Almost all participants (97%) were observed to have at least one difference in medical management and/or GC options following WES. Comparing pre- and post-WES detected significant differences (p ≤ 0.05) in genetic testing, imaging, and metabolic testing regardless of WES results. Participants with positive results also had significant differences in recurrence risk, reproductive options, testing for family members, and support groups. Pre- to post-WES differences were significantly different between participants with positive and negative results in specialist referrals, lifestyle recommendations, recurrence risk, and all GC options (p ≤ 0.05); specifically, participants with positive results were more likely to have differences in these categories. Overall, differences in medical management and/or GC options were observed for participants with both types of WES results (positive and negative). Results from this study may contribute to the understanding of how WES impacts patients and their care and thus improve its utilization.

The relationship between genetic counseling student self-efficacy and clinical training.

Clinical experience is an important part of the training required in genetic counseling graduate programs, but little evidence exists for the number of clinical cases a student may need in order to confidently perform skills. The purpose of this study was to further describe the relationship between genetic counseling student self-efficacy and the number of core cases students log during their training. In this study, second year genetic counseling students nearing the end of their training completed a questionnaire that included the Genetic Counseling Self-efficacy Scale (GCSES) and questions related to the students' clinical experiences. Genetic counseling student self-efficacy was found to be positively associated with the number of core cases the student accumulated during training, with a plateau in GCSES scores between 80 and 100 core cases. These data suggest that 50 cases may not be enough for the average student, but over 100 may be more than needed in order to feel confident in their skills. Genetic counseling programs may benefit from increased flexibility in clinical training to meet the different needs of their trainees. Further studies characterizing the relationship between genetic counseling student self-efficacy and clinical competency, and well as the effectiveness of clinical training by genetic counseling programs, may aid in better understanding the clinical training specifications that best meet the needs of genetic counseling trainees.

Applicability of the Curaçao Criteria for the Diagnosis of Hereditary Hemorrhagic Telangiectasia in the Pediatric Population.

OBJECTIVE: To evaluate the accuracy of the clinical Curaçao criteria in the diagnosis of hereditary hemorrhagic telangiectasia (HHT) in children and adolescents. STUDY DESIGN: This was a retrospective, multicenter chart review of 673 patients evaluated between 2002 and 2016; 290 were eligible for the study. Genetic testing for a pathogenic mutation was considered the gold standard against which the clinical Curaçao criteria were compared. Patients were divided into 4 age categories: 0-5, 6-10, 11-15, and 16-21-years. Sensitivity and specificity were calculated for each age group, and for the overall population. RESULTS: Overall the Curaçao criteria had a sensitivity of 68% (95% CI 60%-76%) and a specificity of 98% (95% CI 91%-100%). Sensitivity was lowest in the 0- to 5-year group, and increased with advancing age. The Curaçao criteria had the highest sensitivity in the 16- to 21-year-olds. Specificity was 100% in all age groups except for the 11- to 15-year-olds. CONCLUSIONS: 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).

Development and Validation of the Genetic Counseling Self-Efficacy Scale (GCSES).

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 Relationship Between the Supervisory Working Alliance and Student Self-Efficacy in Genetic Counseling Training.

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.

Clinical delineation of the PACS1-related syndrome--Report on 19 patients.

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.

Measuring the Effectiveness of a Genetic Counseling Supervision Training Conference.

Genetic counselors who receive formal training report increased confidence and competence in their supervisory roles. The effectiveness of specific formal supervision training has not been assessed previously. A day-long GC supervision conference was designed based on published supervision competencies and was attended by 37 genetic counselors. Linear Mixed Model and post-hoc paired t-test was used to compare Psychotherapy Supervisor Development Scale (PSDS) scores among/between individuals pre and post conference. Generalized Estimating Equation (GEE) model and post-hoc McNemar's test was used to determine if the conference had an effect on GC supervision competencies. PSDS scores were significantly increased 1 week (p < 0.001) and 6 months (p < 0.001) following the conference. For three supervision competencies, attendees were more likely to agree they were able to perform them after the conference than before. These effects remained significant 6 months later. For the three remaining competencies, the majority of supervisors agreed they could perform these before the conference; therefore, no change was found. This exploratory study showed this conference increased the perceived confidence and competence of the supervisors who attended and increased their self-reported ability to perform certain supervision competencies. While still preliminary, this supports the idea that a one day conference on supervision has the potential to impact supervisor development.

The Relationship between the Supervision Role and Compassion Fatigue and Burnout in Genetic Counseling.

Many genetic counselors provide supervision to students during their career. Previous studies have shown genetic counselors, in general, are at increased risk for developing compassion fatigue. The purpose of this study was to determine if there was a difference in compassion fatigue and burnout levels in genetic counselors who currently supervise compared to genetic counselors who do not. Genetic counselors who currently practice in a clinical setting (N = 391) completed an online survey containing demographic questions, the Professional Quality of Life Scale, the State-Trait Anxiety Inventory, and questions specific to the genetic counselor's experiences with supervision. Overall, when controlling for trait-anxiety, the supervision role by itself was not independently associated with the risk for compassion fatigue and burnout among genetic counselors. Within supervisors, however, there were several factors which were associated with this risk. Those with less supervision experience reported more secondary traumatic stress. Those supervisors reporting less confidence had decreased compassion satisfaction. Those with less experience or less confidence in their supervision role were most likely to be at increased risk for developing compassion fatigue. Training in supervision and support for dealing with compassion fatigue and burnout may be beneficial to supervisors with less experience.

Barriers impacting the utilization of supervision techniques in genetic counseling.

Clinical supervision is an essential element in training genetic counselors. Although live supervision has been identified as the most common supervision technique utilized in genetic counseling, there is limited information on factors influencing its use as well as the use of other techniques. The purpose of this study was to identify barriers supervisors face when implementing supervision techniques. All participants (N = 141) reported utilizing co-counseling. This was most used with novice students (96.1%) and intermediate students (93.7%). Other commonly used techniques included live supervision where the supervisor is silent during session (98.6%) which was used most frequently with advanced students (94.0%), and student self-report (64.7%) used most often with advanced students (61.2%). Though no barrier to these commonly used techniques was identified by a majority of participants, the most frequently reported barriers included time and concern about patient's welfare. The remaining supervision techniques (live remote observation, video, and audio recording) were each used by less than 10% of participants. Barriers that significantly influenced use of these techniques included lack of facilities/equipment and concern about patient reactions to technique. Understanding barriers to implementation of supervisory techniques may allow students to be efficiently trained in the future by reducing supervisor burnout and increasing the diversity of techniques used.

The impact of supervision training on genetic counselor supervisory identity development.

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.

Hereditary hemorrhagic telangiectasia (HHT): a practical guide to management.

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.

Common and recurrent HPGD mutations in Caucasian individuals with primary hypertrophic osteoarthropathy.

OBJECTIVE: Homozygous recessive germline mutations of the 15-hydroxyprostaglandin dehydrogenase (HPGD) gene, encoding 15-hydroxyprostaglandin dehydrogenase, result in persistent elevation of circulating PGE(2) levels, causing the syndrome of primary hypertrophic osteoarthropathy (PHO). Homozygous HPGD mutations have so far been reported in 10 families, all but one displaying parental consanguinity. Only two of these families were of European origin. We wished to determine the role of HPGD in causing PHO in non-consanguineous European families. METHODS: Five previously unreported families of Caucasian European origin, with one or more individuals affected with typical PHO, were characterized clinically and by complete sequencing of the HPGD coding exons. RESULTS: Biallelic HPGD mutations were identified in affected individuals in all the five families, confirming a very specific association of this phenotype with HPGD mutations. The previously described c.175_176delCT frameshift mutation was observed in association with two different alleles of an adjacent single nucleotide polymorphism. CONCLUSIONS: 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.