Mitochondrial replacement therapy: Genetic counselors' experiences, knowledge, and opinions.

Mitochondrial disorders affect at least 1 in 5,000 individuals worldwide and are often incurable and fatal. Mitochondrial replacement therapy (MRT) is an in vitro fertilization technique used to prevent the transmission of mitochondrial disorders. Currently, MRT is the only approach that provides mothers who carry a pathogenic variant in their mitochondrial DNA (mtDNA), the opportunity to have a biological child without a mitochondrial disease. MRT involves the combination of nuclear DNA from the egg of the carrier mother and the cytoplasm from an oocyte donor, which contains healthy mitochondria. While MRT was approved for use in the UK in 2015, the ban on congressional funding for research on 'heritable genetic modification' has made MRT unavailable within the US borders. This survey-based study aimed to describe genetic counselors' experience, knowledge, and opinions about MRT. Additionally, we also assessed whether genetic counselors' comfort discussing MRT with patients, and feelings about clinical use of MRT in the United States changed after providing information about MRT compared with baseline. Responses were received from 139 genetic counselors in North America. Findings indicate low awareness and knowledge about MRT among participants. However, more participants expressed comfort with discussing MRT with patients and more participants were able to form opinions about statements about MRT after they were provided with information about MRT. This study is the first to assess genetic counselors' opinions toward MRT and suggests the need for more education about novel technologies such as MRT among genetic counselors.

Genetic counselor perceptions of genetic counseling session goals: a validation study of the reciprocal-engagement model.

Although some researchers have attempted to define genetic counseling practice goals, no study has obtained consensus about the goals from a large sample of genetic counselors. The Reciprocal-Engagement Model (REM; McCarthy Veach, Bartels & LeRoy, 2007) articulates 17 goals of genetic counseling practice. The present study investigated whether these goals could be generalized as a model of practice, as determined by a larger group of clinical genetic counselors. Accordingly, 194 genetic counselors were surveyed regarding their opinions about the importance of each goal and their perceptions of how frequently they achieve each goal. Mean importance ratings suggest they viewed every goal as important. Factor analysis of the 17 goals yielded four factors: Understanding and Appreciation, Support and Guidance, Facilitative Decision-Making, and Patient-Centered Education. Patient-Centered Education and Facilitative Decision-Making goals received the highest mean importance ratings. Mean frequency ratings were consistently lower than importance ratings, suggesting genetic counseling goals may be difficult to achieve and/or not applicable in all situations. A number of respondents provided comments about the REM goals that offer insight into factors related to implementing the goals in clinical practice. This study presents preliminary evidence concerning the validity of the goals component of the REM.

Four new patients with Gomez-Lopez-Hernandez syndrome and proposed diagnostic criteria.

Gomez-Lopez-Hernandez syndrome (GLHS) is a rare neurocutaneous disorder. We are aware of thirty previously reported cases. We present four additional patients with this condition. Previously reported patients have shown the hallmark triad of rhombocephalosynapsis, trigeminal anesthesia, and bilateral parietal or parieto-occipital alopecia. Rhombencephalosynapsis consists of agenesis of the cerebellar vermis, fusion of the cerebellar hemispheres, and the dentate nuclei. The gene or genes responsible for GLHS remain unknown. Alopecia is seen in all previously reported cases of GLHS. Additional craniofacial findings such as low-set and posteriorly rotated ears, midface retrusion, craniosynostosis, and brachyturricephaly are also very common in this syndrome. Trigeminal anesthesia, reported in the original three patients, is seen in just over half of reported patients. Most patients with GLHS have motor delays, intellectual disability, and hypotonia. Unusual stereotypic movements of the head are seen in many patients with GLHS. Neuroimaging of patients with GLHS shows rhombencephalosynapsis is universally present, with ventriculomegaly/hydrocephalus and cerebellar hypoplasia being common. We propose that rhombencephalosynapsis and scalp alopecia are necessary, but by themselves not sufficient, for a diagnosis of GLHS. Additional findings of trigeminal anesthesia or one of two major craniofacial findings (brachycephaly and/or turricephaly or midface retrusion) are sufficient to make a diagnosis of GLHS. Additional categories of probable and possible GLHS are proposed for patients whose examination may be compatible with a diagnosis of GLHS, but CNS imaging has not yet been obtained. © 2013 Wiley Periodicals, Inc.

Late-onset ornithine transcarbamylase deficiency: An under recognized cause of metabolic encephalopathy.

INTRODUCTION: Ornithine transcarbamylase deficiency is the most common inherited disorder of the urea cycle, has a variable phenotype, and is caused by mutations in the OTC gene. We report three cases of ornithine transcarbamylase deficiency to illustrate the late-onset presentation of this disorder and provide strategies for diagnosis and treatment. The patients were maternal first cousins, presenting with hyperammonemia and obtundation. Urea cycle disorder was not initially suspected in the first patient, delaying diagnosis. RESULTS: Sequencing of the OTC gene showed a novel missense mutation, c.563G > C (p.G188A). Numerous family members were found to carry this mutation, which shows a trend toward later onset. Each urea cycle disorder has its own unique pattern of biochemical abnormalities, which differ from non-metabolic causes of critical illness. CONCLUSION: Regardless of age, clinical suspicion of a urea cycle disorder is important in encephalopathic patients to ensure quick diagnosis and definitive treatment of the underlying inborn error of metabolism.