The Genetics Journey: A Case Report of a Genetic Diagnosis Made 30 Years Later

Mandibulofacial dysostosis with microcephaly (MFDM) is a rare autosomal dominant condition that was first described in 2006. The causative gene, EFTUD2, identified in 2012. We report on a family that initially presented to a pediatric genetics clinic in the 1980s for evaluation of multiple congenital anomalies. Re‐evaluation of one member thirty years later resulted in a phenotypic and molecularly confirmed diagnosis of MFDM. This family’s clinical histories and the novel EFTUD2 variant identified, c.1297_1298delAT (p.Met433Valfs*17), add to the literature about MFDM. This case presented several genetic counseling challenges and highlights that “the patient” can be multiple family members. We discuss testing considerations for an unknown disorder complicated by the time constraint of the patient’s daughter’s pregnancy and how the diagnosis changed previously provided recurrence risks. Of note, 1) the 1980s clinic visit letters provided critical information about affected family members and 2) the patient’s husband’s internet search of his wife’s clinical features also yielded the MFDM diagnosis, illustrating the power of the internet in the hands of patients. Ultimately, this case emphasizes the importance of re‐evaluation given advances in genetics and the value of a genetic diagnosis for both patient care and risk determination for family members.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147210/1/jgc40894.pd

Neural Substrates of Spontaneous Musical Performance: An fMRI Study of Jazz Improvisation

To investigate the neural substrates that underlie spontaneous musical performance, we examined improvisation in professional jazz pianists using functional MRI. By employing two paradigms that differed widely in musical complexity, we found that improvisation (compared to production of over-learned musical sequences) was consistently characterized by a dissociated pattern of activity in the prefrontal cortex: extensive deactivation of dorsolateral prefrontal and lateral orbital regions with focal activation of the medial prefrontal (frontal polar) cortex. Such a pattern may reflect a combination of psychological processes required for spontaneous improvisation, in which internally motivated, stimulus-independent behaviors unfold in the absence of central processes that typically mediate self-monitoring and conscious volitional control of ongoing performance. Changes in prefrontal activity during improvisation were accompanied by widespread activation of neocortical sensorimotor areas (that mediate the organization and execution of musical performance) as well as deactivation of limbic structures (that regulate motivation and emotional tone). This distributed neural pattern may provide a cognitive context that enables the emergence of spontaneous creative activity

Prospective teachers navigating intersecting communities of practice: early school placement

An issue of particular concern in mathematics teacher education is the relationship between theory and practice, and the nature of university–school partnerships. We report here on results from a research project answering the call for a more systematic understanding of the practice learning context. The study focuses on the new Norwegian elementary teacher education programme and highlights the difficulties involved in connecting theory and practice and how prospective teachers may be supported in this respect. Focus group interviews involving 51 first-year prospective teachers and 25 teacher–mentors investigated early school placements, specifically prospective teachers’ positions in the classroom as teachers of mathematics, and the ways in which the mentoring relationship supported their developing role. Taking a communities of practice perspective, we found that the idea of movement across intersecting and sometimes conflicting communities of practice is helpful in aiding our understanding of the difficulty of connecting theory and practice. Additionally, variations in mentoring styles and perceptions of prospective teachers’ mathematics and pedagogic knowledge competencies play a part in some prospective teachers’ difficulties in taking up a role as legitimate peripheral participant in the school. We conclude by considering ways in which prospective teachers might be better supported to cope with school placement

Noninvasive Assessment of Preclinical Atherosclerosis

Initially considered as a semipermeable barrier separating lumen from vessel wall, the endothelium is now recognised as a complex endocrine organ responsible for a variety of physiological processes vital for vascular homeostasis. These include the regulation of vascular tone, luminal diameter, and blood flow; hemostasis and thrombolysis; platelet and leucocyte vessel-wall interactions; the regulation of vascular permeability; and tissue growth and remodelling. The endothelium modulates arterial stiffness, which precedes overt atherosclerosis and is an independent predictor of cardiovascular events. Unsurprisingly, dysfunction of the endothelium may be considered as an early and potentially reversible step in the process of atherogenesis and numerous methods have been developed to assess endothelial status and large artery stiffness. Methodology includes flow-mediated dilatation of the brachial artery, assessment of coronary flow reserve, carotid intimamedia thickness, pulse wave analysis, pulse wave velocity, and plethysmography. This review outlines the various modalities, indications, and limitations of available methods to assess arterial dysfunction and vascular risk

At the bottom of the differential diagnosis list: unusual causes of pediatric hypertension

Hypertension affects 1–5% of children and adolescents, and the incidence has been increasing in association with obesity. However, secondary causes of hypertension such as renal parenchymal diseases, congenital abnormalities and renovascular disorders still remain the leading cause of pediatric hypertension, particularly in children under 12 years old. Other less common causes of hypertension in children and adolescents, including immobilization, burns, illicit and prescription drugs, dietary supplements, genetic disorders, and tumors will be addressed in this review

All-sky search for gravitational-wave bursts in the second joint LIGO-Virgo run

We present results from a search for gravitational-wave bursts in the data collected by the LIGO and Virgo detectors between July 7, 2009 and October 20, 2010: data are analyzed when at least two of the three LIGO-Virgo detectors are in coincident operation, with a total observation time of 207 days. The analysis searches for transients of duration < 1 s over the frequency band 64-5000 Hz, without other assumptions on the signal waveform, polarization, direction or occurrence time. All identified events are consistent with the expected accidental background. We set frequentist upper limits on the rate of gravitational-wave bursts by combining this search with the previous LIGO-Virgo search on the data collected between November 2005 and October 2007. The upper limit on the rate of strong gravitational-wave bursts at the Earth is 1.3 events per year at 90% confidence. We also present upper limits on source rate density per year and Mpc^3 for sample populations of standard-candle sources. As in the previous joint run, typical sensitivities of the search in terms of the root-sum-squared strain amplitude for these waveforms lie in the range 5 10^-22 Hz^-1/2 to 1 10^-20 Hz^-1/2. The combination of the two joint runs entails the most sensitive all-sky search for generic gravitational-wave bursts and synthesizes the results achieved by the initial generation of interferometric detectors.Comment: 15 pages, 7 figures: data for plots and archived public version at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=70814&version=19, see also the public announcement at http://www.ligo.org/science/Publication-S6BurstAllSky

Caracterização etiológica e clínica das neurites ópticas infecciosas

As neurites ópticas infecciosas (NOI) foram estudadas em relação aos aspectos etiológicos, epidemiológicos e clínicos, com o intuito de detectar características que possam diferencia-las das neurites ópticas desmielinizantes (NOD), que apresentam nítida tendência para conversão em esclerose múltipla. Entre 105 casos de NOI, 51 não apresentavam qualquer evidência de envolvimento da coróide ou retina e poderiam ser confundidos com NOD. Envolvimento bilateral foi encontrado em 23 pacientes (45,1%), sendo simultâneo em 18 (78,3%) casos. A relação entre sexos foi 2M: IF. As idades variaram ente 1 a 82 anos, com mediana de 34,8 anos. Um terço dos pacientes tinha idades até 20 anos, e em um terço dos pacientes as idades eram igual ou maior que 50 anos. Sífilis foi encontrada em 19 pacientes sendo a causa mais comum das NOI, enquanto infecções virais diversas foram responsabilizadas em 41,2%. A acuidade visual foi gravemente afetada na maioria dos casos, sendo pior que 20/200 em 57,3% dos olhos acometidos. Distúrbios da visão cromática foram encontrados em 91,8%, enquanto o exame do campo visual revelou anormalidades em 92,6% dos olhos, predominando os defeitos centrais (40,7%). O disco óptico estava anormal em 90,5% dos olhos examinados, sendo atrofia óptica o principal achado fundoscópico. O presente estudo demonstra que a maior tendência a bilateralidade e simultaneidade das NOI, sua maior prevalência no sexo masculino, na infância e em adultos após os 50 anos de idade, assim como a maior severidade do comprometimento das funções visuais diferem substancialmente das características relatadas nas NOD. O conhecimento destas diferenças pode auxiliar na diferente abordagem terapêutica e prognostica das duas distintas condições.Fifty-one patients with infectious optic neuritis (ION) with no associated choroidal or retinal involvement were studied in relation to the etiologic agents, and to the epidemiological and clinical features to look up features which could be used to distinct them from the demyelinating optic neuritis (DON) which have a well-known tendency to convert to multiple sclerosis. Bilateral involvement was found in 23 patients (45.1 %), simultaneously in 18 cases. Sex distribution was 2M:1F. The ages ranged from 1 to 82 years (median 34.8); 1/3 of the patients were younger than 20 and 1/3 were 50 years of age or older. Syphilis was found in 19 patients being the single most common etiology, whereas viral infetions were found in 41.2% of the cases. Visual acuity was severely damaged in most patients and was worse than 20/200 in 57.3% of the involved eyes. Color vision was affected in 91.8%. Visual field defects were found in 92.2%, with predominance of the central defects (40.7%). The optic disc was abnormal in 90.5% of the eyes. This study clearly demonstrates that ION and DON have distinct epidemiological and clinical features. The awareness of these differences may help clinicians to follow different paths for the correct diagnosis and appropriate treatment and prognostic orientation of their patients