"Good practices" in pediatric clinical care for disorders/differences of sex development.

PURPOSE: To define, benchmark, and publicize elements of quality care (i.e., "good practices") for pediatric patients with disorders/differences of sex development (DSD). METHODS: Principles of quality care were identified by literature review; consensus exists for 11 good practices and adherence was evaluated through online survey of 21 North American clinical sites. RESULTS: Strong uptake was observed for many practices, particularly specialty participation (n ≥ 17 of 21 sites for most core specialties); point of contact (n = 18); expertise in gender dysphoria/dissatisfaction (n = 20); and DSD-specific continuing medical education (n = 18). Greater variability was apparent for frequency of peer support referrals (n = 12 universally practiced); standardized questionnaires for routine assessment of psychosocial adaptation (n = 13) and gender development (n = 10); consistently clarifying patient/family values in decision-making (n = 15); genital exam protocols that exclude trainee education as primary reason (n = 15); and internal patient-tracking efforts (n = 5-10 of 20 sites). CONCLUSION: This study employed a novel approach to designate DSD good practices and identified areas of consistency and variation in these DSD clinical practices. Good practice benchmarking facilitates quality assessment within and across sites, promotes continuous improvement, and empowers stakeholders in locating and delivering high quality care.

Family Perspectives on Newborn Screening for X-Linked Adrenoleukodystrophy in California.

X-linked adrenoleukodystrophy (ALD) is caused by gene variants in the ABCD1 gene, resulting in a varied clinical spectrum. Males with ALD present with symptoms ranging from isolated adrenal insufficiency and slowly progressive myelopathy to severe cerebral demyelination. Females who are heterozygous for ALD typically develop milder symptoms by late adulthood. Treatment for adrenal insufficiency associated with ALD exists in the form of cortisol, and cerebral ALD may be treated with stem cell transplantation. Currently, there is no treatment for myelopathy. Since 2013, at least 14 states have added ALD to their newborn screening (NBS) panel, including California in 2016. We examined the impact of a positive NBS result for ALD on families in California. Qualitative interviews were conducted with mothers of 10 children who were identified via NBS for ALD. Interviews were transcribed verbatim and analyzed using thematic analysis by two coders. Mothers felt strongly that ALD should be included on California's NBS panel; however, many expressed concerns over their experience. Themes included stress at initial phone call, difficulty living with uncertainty, concerns regarding mental health support, and desire for more information on disease progression, treatments and clinical trials. Mothers exhibited diverse coping strategies, including relying on faith, information seeking, and maintaining hope. Mothers' recommendations for healthcare providers included: educating providers making the initial phone call, providing patient-friendly resources, offering information about ongoing research, and streamlining care coordination. Advice for parents of children with ALD focused on staying hopeful and appreciating the time they have with their children. As more states add ALD to their NBS panel, it is important to improve the current model to promote family resiliency and autonomy.

Genetic Counselor and Healthcare Interpreter Perspectives on the Role of Interpreters in Cancer Genetic Counseling.

Cancer genetic counseling (CGC) combines psychosocial counseling and genetic education provided by genetic counselors to patients and families who have a history of cancer and are considering or have undergone genetic testing for hereditary cancer syndromes. The quantity and complexity of information provided can be challenging for any patient, but is even more so for those with limited English proficiency (LEP). This exploratory study investigated healthcare interpreters' and genetic counselors' perspectives on the role of interpreters in providing care to LEP patients during CGC. Through a survey of 18 interpreters and conventional content analysis of semi-structured interviews with 11 interpreters and 10 GCs at two California public hospitals, we found that: 1) interpreters viewed their role as patient advocate, cultural broker, and emotional support, not simply a conduit; 2) interpreters were challenged by remote interpretation, lack of genetic knowledge, and the emotional content of encounters; 3) interpreters and GCs held conflicting views of the value of counselors' limited Spanish knowledge; and 4) trust, the foundation of the interpreter-provider dyad, was often lacking. The challenges identified here may result in poor healthcare experiences and outcomes for LEP patients. As genomics becomes more widespread and more LEP patients encounter CGC, the role of healthcare interpreters in facilitating effective communication must be further defined in order to facilitate better working relationships between interpreters and genetic counselors, and optimal communication experiences for patients.

Cancer Counseling of Low-Income Limited English Proficient Latina Women Using Medical Interpreters: Implications for Shared Decision-Making.

In cancer genetic counseling (CGC), communication across language and culture challenges the model of practice based on shared decision-making. To date, little research has examined the decision-making process of low-income, limited English proficiency (LEP) patients in CGC. This study identified communication patterns in CGC sessions with this population and assessed how these patterns facilitate or inhibit the decision-making process during the sessions. We analyzed 24 audio recordings of CGC sessions conducted in Spanish via telephone interpreters at two public hospitals. Patients were referred for risk of hereditary breast and ovarian cancer; all were offered genetic testing. Audio files were coded by two bilingual English-Spanish researchers and analyzed using conventional content analysis through an iterative process. The 24 sessions included 13 patients, 6 counselors, and 18 interpreters. Qualitative data analyses identified three key domains - Challenges Posed by Hypothetical Explanations, Misinterpretation by the Medical Interpreter, and Communication Facilitators - that reflect communication patterns and their impact on the counselor's ability to facilitate shared decision-making. Overall, we found an absence of patient participation in the decision-making process. Our data suggest that when counseling LEP Latina patients via medical interpreter, prioritizing information with direct utility for the patient and organizing information into short- and long-term goals may reduce information overload and improve comprehension for patient and interpreter. Further research is needed to test the proposed counseling strategies with this population and to assess how applicable our findings are to other populations.

Lynch syndrome patients' views of and preferences for return of results following whole exome sequencing.

Whole exome sequencing (WES) uses next generation sequencing technology to provide information on nearly all functional, protein-coding regions in an individual's genome. Due to the vast amount of information and incidental findings that can be generated from this technology, patient preferences must be investigated to help clinicians consent and return results to patients. Patients (n = 19) who were previously clinically diagnosed with Lynch syndrome, but received uninformative negative Lynch syndrome genetic results through traditional molecular testing methods participated in semi-structured interviews after WES testing but before return of results to explore their views of WES and preferences for return of results. Analyses of interview results found that nearly all participants believed that the benefits of receiving all possible results generated from WES outweighed the undesirable effects. The majority of participants conveyed that relative to coping with a cancer diagnosis, information generated from WES would be manageable. Importantly, participants' experience with Lynch syndrome influenced their notions of genetic determinism, tolerance for uncertain results, and family communication plans. Participants would prefer to receive WES results in person from a genetic counselor or medical geneticist so that an expert could help explain the meaning and implications of the potentially large quantity and range of complicated results. These results underscore the need to study various populations with regard to the clinical use of WES in order to effectively and empathetically communicate the possible implications of this new technology and return results.

International genetic counseling students' perspective on their training experience in the United States.

International students face social, psychological and academic challenges upon moving to a foreign country to pursue higher education. Clinical disciplines such as genetic counseling present additional challenges adapting to an unfamiliar health care system and different interactions and expectations with patients and colleagues. This study used semi-structured interviews to identify challenges that international genetic counseling students face during training in the United States. Eight international genetic counseling alumni who graduated from U.S.-accredited programs were interviewed. Participants stated that the U.S. academic system was unfamiliar-class participation and paper-writing required the greatest adjustment. There was a need for help in understanding social norms in academic settings. Clinically, they were unfamiliar with the dynamics and communication style of U.S. families. Non-native English speakers experienced greater difficulty in all areas. Most participants reported that they were uncomfortable asking for help in transitioning to life, study and work. Participants identified mentorship programs for international students as potentially useful in clarifying expectations in academic and clinical settings. These results may assist international students preparing to study genetic counseling in the U.S. and may help genetic counseling training programs identify the academic and clinical challenges faced by international students.

Genotype-phenotype association studies of chromosome 8p inverted duplication deletion syndrome.

Individuals diagnosed with chromosome 8p inverted duplication deletion (invdupdel(8p)) manifest a wide range of clinical features and cognitive impairment. The purpose of this study is to employ array CGH technology to define more precisely the cytogenetic breakpoints and regions of copy number variation found in several individuals with invdupdel(8p), and compare these results with their neuropsychological characteristics. We examined the cognitive-behavioral features of two male and two female children, ages 3-15 years, with invdupdel(8p). We noted cognitive deficits that ranged from mild to severe, and adaptive behavior composites that ranged from significantly to substantially lower than adequate levels. CARS scores, a measure of autistic behavior, identified three children with autism or autistic-like features. Three of the four children exhibited attention deficits and hyperactivity consistent with a DSM-IV-TR diagnosis of ADHD. One child showed extreme emotional lability. Interestingly, intellectual disability was not correlated with deletion size, nor was the deletion location associated with the autistic phenotype. On the other hand, the duplication length in 8p21.1/8p22 was associated with cognitive deficit. In addition, a small locus of over-expression in 8p21.3 was common for all three participants diagnosed as autistic. A limitation of the study is its small sample size. Further analyses of the deleted and over-expressed regions are needed to ascertain the genes involved in cognitive function and, possibly, autism.

Cognitive-behavioral features of Wolf-Hirschhorn syndrome and other subtelomeric microdeletions.

Wolf-Hirschhorn syndrome (WHS) is a complex congenital malformation produced by a loss of genomic material at the locus 4p16.3. In addition to its dysmorphic features, the deletion produces a range of intellectual disability (ID). Many clinical aspects of WHS are well-characterized; however, the cognitive-behavioral characteristics have been rarely examined in a systematic fashion. The purpose of our study was to examine the cognitive-behavioral features of WHS and to compare them to children with other subtelomeric deletions that also produce ID. We recruited 45 children with subtelomeric deletions and examined their cognitive-behavioral abilities using a neuropsychological assessment battery composed of standardized instruments. Nineteen children were diagnosed with WHS and 26 children with one of three other subtelomeric deletions-11q25 (Jacobsen syndrome), deletion 2q37, and inversion duplication deletion 8p21-23. We found children with WHS to be more severely impacted cognitively than children from any of the other groups. Their overall adaptive behavior was lower as well. However, children with WHS exhibit strengths in socialization skills comparable to the levels attained by the other groups we assessed. Importantly, the proportion of children with WHS with autism or autistic-like features is significantly lower than the rates of autism found in the other subtelomeric disorders we examined.

Cognitive-behavioral features of children with Wolf-Hirschhorn syndrome: preliminary report of 12 cases.

As a subset of genetic abnormalities, subtelomeric deletions have been found in 7-10% of individuals with mental retardation (MR). One subtelomeric deletion, Wolf-Hirschhorn syndrome (WHS), causes mild to severe MR, but the cognitive-behavioral features of individuals with WHS have not been studied systematically. To that end, we administered a comprehensive cognitive-behavioral battery to 12 children with WHS, ages 4-17 years, who also had some expressive language. Using the Stanford-Binet (4th Edition), we found cognitive deficits ranged from mild to severe, with mean IQ = 44.1. Interviewing parents with the Vineland Adaptive Behavior Scales, we found mean adaptive behavior score (DQ) = 37.3, with females exhibiting slightly higher scores than males. Cognitive profiles indicated relative strengths in Verbal and Quantitative Reasoning. Adaptive behavior profiles noted significant relative strengths in the Socialization Domain. These cognitive-behavioral profiles differed from children with other subtelomeric deletion syndromes, 2q37 or 8p23. Attention deficits and hyperactivity (ADHD) were observed in 7/12 (58%) of the children we tested. One child attained a score on the Child Autism Rating Scale (CARS) suggestive of mild autism. We conclude that different genetic disorders, which cause MR, produce diverse cognitive-behavioral profiles. Consequently, cognitive-behavioral profiles of children with MR need to be assessed more comprehensively.

TelePresence Confocal Laser Scanning Microscopy.

The advent of the Internet has allowed the development of remote access capabilities to a growing variety and number of microscopy systems. To date, the confocal microscope has not been included among these systems. At the California State University (CSU) Confocal Microscopy Core Facility, we have established a remote access confocal laser scanning microscope facility that allows users with virtually any type of computer platform to connect to our system. Our Leica TCS NT confocal system is accessible to any authorized user via the Internet by using a free software program called VNC (Virtual Network Computing). Once connectivity is established, remote users are able to control virtually all the functions to conduct real-time image analysis and quantitative assessments of their specimen. They can also move the motorized stage to view different regions of their specimen by using a software program associated with the stage. At the end of the session, all files generated during the session can be downloaded to the user's computer from a link on the CSU confocal website. A number of safeguard features have been developed to ensure security and privacy of data acquired during a remote session.