Differences in genetic counseling student responses to intense patient affect: A study of students in North American programs.

Research indicates genetic counseling patients often experience intense emotions. No studies, however, have investigated how genetic counseling students respond to patient affect. This survey study investigated student responses to patient emotions and select factors affecting their responses. One-hundred fifty-one genetic counseling students in North American programs wrote a response to each of three hypothetical prenatal scenarios, identical except for the patient affect expressed (anger, fear, or sadness). They also completed measures of empathy tendency and tolerance of negative affect and demographic questions. Multivariate analysis of covariance (MANCOVA), used to analyze the effects of major study variables on the types of responses given by participants, was significant. Follow-up univariate ANCOVAs indicated small to moderate effect sizes for student clinical experience, race/ethnicity, and relationship status within and across scenarios. For example, as number of patients counseled increased, participants used more feeling reflections and fewer self-involving statements. There were no significant differences in responses due to empathy tendency or affect tolerance. Most common responses were information provision and feeling reflections for the Anger scenario, information provision for the Fear scenario, and influencing responses for the Sadness scenario. Responses to each scenario typically involved multiple thoughts (range: 1-14; means ranged from 3.25 in the Sadness scenario to 3.62 in the Fear scenario). Most students (82%) reported the Anger scenario was the most difficult. Thematic analysis of reasons a scenario was difficult yielded four themes: Discomfort with situation/emotion, Positive countertransference, Uncertain how to respond, and Negative countertransference. Findings that clinical experience affects how participants responded to patient affect support the essential role of applied experience. Findings also support training and supervision to help genetic counseling students in North America learn ways to respond to strong patient emotions and recognize and manage countertransference.

Rare presentation of FDX2-related disorder and untargeted global metabolomics findings.

We present the case of a 20-year-old male with a history of myopathy and multiple episodes of rhabdomyolysis, and lactic acidosis. He needed hemodialysis for severe rhabdomyolysis-related acute renal failure at the time of initial presentation (age 10 years). Exome sequencing detected a homozygous likely pathogenic variant in FDX2 (c.12G>T, p.M4I). The FDX2 gene encodes a mitochondrial protein, ferredoxin 2, that is involved in the biogenesis of Fe-S clusters. Biallelic pathogenic variants in FDX2 have previously been associated with episodic mitochondrial myopathy with or without optic atrophy and reversible leukoencephalopathy. Only two cases with FDX2-related rhabdomyolysis as a predominant feature have been reported in medical literature. Here, we report a third patient with FDX2-related recurrent, severe episodes of rhabdomyolysis and lactic acidosis. He does not have optic atrophy or leukoencephalopathy. This is the oldest patient reported with FDX2-related disorder and he has significantly elevated CK during episodes of rhabdomyolysis. In addition, we describe untargeted global metabolomic findings during an episode of metabolic decompensation, shedding light on the biochemical pathway perturbation associated with this ultra-rare genetic disorder.

Genetic counselor use of self-involving responses in a clinical setting: A qualitative investigation.

Self-involving responses are direct expressions of genetic counselors' here-and-now feelings about/reactions to patients. Strategic, sparing use of self-involving responses may enhance practitioner genuineness, likeability, and trustworthiness, decrease patient anxiety, and increase patient trust and engagement. Conversely, they may threaten patients who are uncomfortable with emotional expression or confuse them about the counselor's intentions. Despite theorized benefits and risks, no study has explored genetic counselor self-involving responses. This study explored whether clinical genetic counselors use self-involving responses with their patients, reasons for doing so, and their perceptions of when and why the responses work well versus poorly. Two-hundred sixty-eight genetic counselors, invited via a National Society of Genetic Counselors e-blast, completed an online screening survey. Eighty-nine percent reported using self-involving responses with patients, and 17 were purposively selected to participate in semi-structured phone interviews. Thematic analysis yielded themes regarding potential benefits, risks, counselor factors and context, and patient factors related to using self-involving responses. Benefits include conveying counselor conditions for facilitating counseling process (e.g., genuineness, building rapport, focusing the session, and encouraging the patient to open-up), and counseling outcomes by validating decision-making. Risks of use include hindering counseling processes and outcomes by misperceiving patient feelings, boundary crossing, and being unduly directive. Factors, both from the counselor and the context of the session, include comfort with the technique, mastery of clinical skills, minimal knowledge of patient emotions, type of counseling session, and counselor practice specialty. Patient factors include prior rapport with the counselor, and patient emotionality and cultural background. Findings underscore the need for training about this technique. Future research could examine patients' perceptions of self-involving statements and differences in self-involvement across practice specialties and counseling modalities.

Genetic developmental disability diagnosed in adulthood: a case report.

BACKGROUND: Developmental disabilities (DD) are an umbrella term for conditions associated with functional impairments in physical, learning, language, or behavior areas. Intellectual disability (ID) is a type of developmental disability that results in delays in cognitive or intellectual functioning, such as reasoning, learning, and problem-solving, and adaptive behaviors including social and practical life skills. DD can be due to a variety of factors, ranging from environmental exposures to genetic mutations, and studies suggest that up to 40% of DDs may be caused by genetic issues. CASE PRESENTATION: In this case study, we present an 18-year-old internationally adopted female Chinese American patient with a known history of developmental delay, intellectual disability, strabismus, and a congenital heart defect who had not been tested for genetic causes of her delay prior to presentation. When evaluated with chromosomal microarray, the patient demonstrated a deletion on the short arm of chromosome 5, an area associated with Cri-du-chat syndrome. This chromosomal deletion was a likely explanation for her history of developmental delays, intellectual disability, and congenital heart defect, in addition to her history of institutionalization and the trauma of multiple caregiver transitions in early childhood. The patient was referred for further evaluation by a geneticist and genetic counselor. CONCLUSIONS: This case highlights that the underlying cause of developmental delay is often multifactorial, and underscores the importance of a full medical evaluation, including genetic testing, for children with intellectual disability. Using this approach, healthcare professionals can identify potential diagnoses and provide more targeted resources to families.

Dual Molecular Effects of Dominant RORA Mutations Cause Two Variants of Syndromic Intellectual Disability with Either Autism or Cerebellar Ataxia.

RORα, the RAR-related orphan nuclear receptor alpha, is essential for cerebellar development. The spontaneous mutant mouse staggerer, with an ataxic gait caused by neurodegeneration of cerebellar Purkinje cells, was discovered two decades ago to result from homozygous intragenic Rora deletions. However, RORA mutations were hitherto undocumented in humans. Through a multi-centric collaboration, we identified three copy-number variant deletions (two de novo and one dominantly inherited in three generations), one de novo disrupting duplication, and nine de novo point mutations (three truncating, one canonical splice site, and five missense mutations) involving RORA in 16 individuals from 13 families with variable neurodevelopmental delay and intellectual disability (ID)-associated autistic features, cerebellar ataxia, and epilepsy. Consistent with the human and mouse data, disruption of the D. rerio ortholog, roraa, causes significant reduction in the size of the developing cerebellum. Systematic in vivo complementation studies showed that, whereas wild-type human RORA mRNA could complement the cerebellar pathology, missense variants had two distinct pathogenic mechanisms of either haploinsufficiency or a dominant toxic effect according to their localization in the ligand-binding or DNA-binding domains, respectively. This dichotomous direction of effect is likely relevant to the phenotype in humans: individuals with loss-of-function variants leading to haploinsufficiency show ID with autistic features, while individuals with de novo dominant toxic variants present with ID, ataxia, and cerebellar atrophy. Our combined genetic and functional data highlight the complex mutational landscape at the human RORA locus and suggest that dual mutational effects likely determine phenotypic outcome.

Infantile gangliosidoses: Mapping a timeline of clinical changes.

BACKGROUND: Infantile gangliosidoses include GM1 gangliosidosis and GM2 gangliosidosis (Tay-Sachs disease, Sandhoff disease). To date, natural history studies in infantile GM2 (iGM2) have been retrospective and conducted through surveys. Compared to iGM2, there is even less natural history information available on infantile GM1 disease (iGM1). There are no approved treatments for infantile gangliosidoses. Substrate reduction therapy using miglustat has been tried, but is limited by gastrointestinal side effects. Development of effective treatments will require identification of meaningful outcomes in the setting of rapidly progressive and fatal diseases. OBJECTIVES: This study aimed to establish a timeline of clinical changes occurring in infantile gangliosidoses, prospectively, to: 1) characterize the natural history of these diseases; 2) improve planning of clinical care; and 3) identify meaningful future treatment outcome measures. METHODS: Patients were evaluated prospectively through ongoing clinical care. RESULTS: Twenty-three patients were evaluated: 8 infantile GM1, 9 infantile Tay-Sachs disease, 6 infantile Sandhoff disease. Common patterns of clinical change included: hypotonia before 6months of age; severe motor skill impairment within first year of life; seizures; dysphagia and feeding-tube placement before 18months of age. Neurodevelopmental testing scores reached the floor of the testing scale by 20 to 28months of age. Vertebral beaking, kyphosis, and scoliosis were unique to patients with infantile GM1. Chest physiotherapy was associated with increased survival in iGM1 (p=0.0056). Miglustat combined with a low-carbohydrate ketogenic diet (the Syner-G regimen) in patients who received a feeding-tube was associated with increased survival in infantile GM1 (p=0.025). CONCLUSIONS: This is the first prospective study of the natural history of infantile gangliosidoses and the very first natural history of infantile GM1. The homogeneity of the infantile gangliosidoses phenotype as demonstrated by the clinical events timeline in this study provides promising secondary outcome measure candidates. This study indicates that overall survival is a meaningful primary outcome measure for future clinical trials due to reliable timing and early occurrence of this event. Combination therapy approaches, instead of monotherapy approaches, will likely be the best way to optimize clinical outcomes. Combination therapy approaches include palliative therapies (e.g., chest physiotherapy) along with treatments that address the underlying disease pathology (e.g. miglustat or future gene therapies).

Clearing the Air: A Qualitative Investigation of Genetic Counselors' Experiences of Counselor-Focused Patient Anger.

Patient anger is challenging for healthcare professionals to manage, particularly when it is directed at them. This study comprises the first in-depth investigation of genetic counselors' experiences with patient anger. Using a brief survey and interview methods, this study explored prevalence and context of patient anger directed at the genetic counselor, how genetic counselors manage patient anger directed at them, and possible thematic differences due to genetic counseling experience. Individuals enrolled in the National Society of Genetic Counselors (NSGC) listserv were invited to participate in a study of their experiences with patient anger directed at them. A majority of survey respondents (95.7 %, 243/254) reported experiencing patient anger directed at them, and 19.4 % reported having feared for their safety because of patient anger. Twenty-two survey respondents were purposively selected to participate in individual interviews. Inductive and cross case analysis yielded prevalent themes concerning patient triggers for anger, including bad news, logistical mishaps, and perceived counselor characteristics. Interview results further suggest unaddressed patient anger negatively affected patient and counselor emotional well-being and hindered genetic counseling goals. Prevalent challenges included genetic counselor attempts to accurately recognize, understand, and effectively manage patient anger without taking it personally. Commonly recommended strategies for addressing anger were empathy (i.e., understanding origins of patient anger), anticipating and acknowledging anger, maintaining personal, professional and legal protection, and debriefing with colleagues. Themes were quite similar across counselor experience levels. The findings underscore the importance of training and continuing education regarding patient anger. Additional findings, practice implications, and research recommendations are presented.

Neuroblastoma in a 17-week fetus: a stimulus for investigation of tumors in a series of 2786 stillbirth and late miscarriages.

Although tumors are an occasional cause of neonatal death and have been reported in stillbirths, there are no studies specifically evaluating the frequency or types of tumors in stillborn infants. We observed metastatic neuroblastoma in a fetus miscarried at 17 weeks of gestational age. Fetal death was attributed to endocrine effects of the tumor causing fetal hypertension, arrhythmia, and/or placental dysfunction. This case, which is the earliest report of a pathologically confirmed neuroblastoma, prompted review of all tumors in the Wisconsin Stillbirth Service Program database. There were 10 lethal and two incidental tumors among the 2,786 stillbirths and second trimester miscarriages in the database for an overall incidence of 1/232, which is about 50 times the incidence of clinically recognized tumors in liveborn infants. The most frequent tumors were teratoma and hemangioma that, while benign, caused death due to high output cardiac failure, hemorrhage into the tumor, or obstruction of vital organs. Only three tumors were malignant, and except for the index case, mechanisms of death were similar to those of the benign tumors. Except for the index case, all were found in the third trimester, suggesting that congenital tumors rarely become lethal until the third trimester. However, it is also possible that tumors may be missed in younger fetuses. The possibility of detecting an unsuspected tumor is yet another reason for autopsy in stillbirths and late miscarriages.

Radiographic evaluation of stillbirth: what does it contribute?

Despite advances in perinatal care, stillbirth is relatively common (1/160 births) and frequently remains unexplained. Most recent protocols for etiologic evaluation of stillbirth either omit radiography or reserve it for infants with obvious skeletal disproportion. Over the past 30 years, the Wisconsin Stillbirth Service Program has collected radiographic images from 2,032 stillbirths and second trimester losses, of which about 25% (517) showed abnormalities. Review of these images by a medical geneticist showed that radiographs yielded a diagnosis in 45% of the infants with abnormalities (11.5% of all radiographs obtained) and were critical, yielding a diagnosis that would otherwise have been missed or incomplete in 1.5% of the total infants. The probability of a diagnosis was not significantly different between miscarriages <20 weeks and stillbirths. Diagnoses were mainly fetal, most commonly sporadic birth defects, idiopathic hydrops, chromosome abnormalities, and skeletal dysplasias, but chorioamnionitis with fetal sepsis, complications of twinning, and cord accidents were also diagnosed radiographically. Radiographs may help direct the use of newer technologies such as chromosomal microarray or gene sequencing. Limiting radiographs to infants with obvious skeletal disproportion would have resulted in many of these diagnoses, including 4/24 skeletal dysplasias, being overlooked. We recommend at least an anterior/posterior babygram film as part of the permanent record of all second trimester losses and stillbirths.