Turner syndrome affects 25–50 per 100,000 females and can involve multiple organs through all stages of life, necessitating multidisciplinary approach to care. Previous guidelines have highlighted ...this, but numerous important advances have been noted recently. These advances cover all specialty fields involved in the care of girls and women with TS. This paper is based on an international effort that started with exploratory meetings in 2014 in both Europe and the USA, and culminated with a Consensus Meeting held in Cincinnati, Ohio, USA in July 2016. Prior to this meeting, five groups each addressed important areas in TS care: 1) diagnostic and genetic issues, 2) growth and development during childhood and adolescence, 3) congenital and acquired cardiovascular disease, 4) transition and adult care, and 5) other comorbidities and neurocognitive issues. These groups produced proposals for the present guidelines. Additionally, four pertinent questions were submitted for formal GRADE (Grading of Recommendations, Assessment, Development and Evaluation) evaluation with a separate systematic review of the literature. These four questions related to the efficacy and most optimal treatment of short stature, infertility, hypertension, and hormonal replacement therapy. The guidelines project was initiated by the European Society of Endocrinology and the Pediatric Endocrine Society, in collaboration with the European Society for Paediatric Endocrinology, the Endocrine Society, the European Society of Human Reproduction and Embryology, the American Heart Association, the Society for Endocrinology, and the European Society of Cardiology. The guideline has been formally endorsed by the European Society of Endocrinology, the Pediatric Endocrine Society, the European Society for Paediatric Endocrinology, the European Society of Human Reproduction and Embryology and the Endocrine Society. Advocacy groups appointed representatives who participated in pre-meeting discussions and in the consensus meeting.
Jerry Pethick (1935–2003) was one of the first artists to experiment with holography in the mid 1960's. He was a close friend and collaborator with Lloyd Cross of Multiplex fame. Pethick and Cross ...started the School of Holography in San Francisco California on Shotwell Street. Pethick is known for building the first sand optics isolation table and writing the first holography handbook describing how to build such a system and create holograms with it. This paper offers some of the missing history of his accomplishments.
•There is evidence of underlying neuromuscular abnormalities in PURA syndrome.•We demonstrate an irritable myopathy by electromyography in PURA syndrome.•There is a potential therapeutic role of ...pyridostigmine in PURA-related hypotonia.
PURA syndrome is a rare, clinically heterogeneous disorder characterized by a wide spectrum of neurodevelopmental problems, and occasionally congenital heart defects, urogenital malformations, skeletal abnormalities and endocrine disorders. We describe the hospital course, diagnostic evaluations as well as neurologic and neuromuscular follow up of an infant diagnosed with PURA syndrome based on a pathogenic deletion at c.697_699 (p.Phe233del) of the PURA gene identified on whole exome sequencing. Upon initial examination, fluctuation of neuromuscular tone and reflexes were noted in conjunction with hypotonia and severe apneic episodes, suggestive of neuromuscular junction involvement. A definitive role of the neuromuscular junction has not been previously reported with PURA syndrome. The infant was started on pyridostigmine, an acetylcholinesterase inhibitor, with significant improvement in neuromuscular tone and motor movements. In addition, pyridostigmine also resulted in resolution of apneas and improved respiratory status which suggests its potential therapeutic role in patients with PURA syndrome.
PURA syndrome is caused by heterozygous de novo pathogenic variants in PURA. It is characterized by moderate to severe neurodevelopmental disability with a wide clinical spectrum and an evolving ...phenotype. We present two individuals with genetically confirmed PURA syndrome who had severe neonatal signs and symptoms and a novel phenotype suggestive of neuromuscular junction pathology. We demonstrate that PURA syndrome shares features consistent with a congenital myasthenic syndrome; we thus recommend electrodiagnostic study in neonates and infants with PURA syndrome, and consideration of salbutamol as a therapeutic option.
Abstract
Constitutional mismatch repair deficiency (CMMRD) is a rare inherited cancer predisposition syndrome caused by bi-allelic mutations in one of four mismatch repair genes.1 Individuals with ...CMMRD are at increased risk for childhood-onset brain tumors, hematologic malignancies, gastrointestinal tumors and often have café-au-lait macules (CALMS).2,3 Diagnosis is frequently delayed due to overlapping phenotype with neurofibromatosis 1 (NF1).4,5,6 Additionally, molecular diagnosis and medical management can be challenging when variants of uncertain significance (VUS) are found.7,8,9,10,11 We present an 11-month-old infant, initially evaluated at an outside facility for multiple CALMs and diagnosed with NF1. He subsequently presented with a posterior fossa mass and subtotal resection was performed. Final pathology was desmoplastic medulloblastoma (DM), SHH with P53 genotype. Following chemotherapy, he underwent near total resection. Pathology revealed gangliocytic/gangliomatous differentiation. He subsequently progressed and received radiation and chemotherapy. Due to patient and family history of CALMs, germline mutation analysis was performed and revealed pathogenic variant in one copy of PMS2 (deletion of exon 12) and a VUS in the other copy of PMS2 (p.Ser815Leu). The second copy was felt to be pathogenic based on review of databases and missense change causing a large change in a well conserved area of the gene, diagnostic of CMMRD. The VUS was confirmed paternal and consistent with father’s family history of colon cancer. The pathogenic variant was maternal. CALMs can be indicative of a cancer predisposition syndrome, thus when a child has multiple CALMs or has CALMs and malignancy, clinicians should consider testing for CMMRD and overlapping disorders.
Turner syndrome affects 50 per 100,000 females, affects multiple organs through all stages of life, necessitating multidisciplinary care. This guideline extends previous ones and includes important ...new advances, within diagnostics and genetics, estrogen treatment, fertility, co-morbidities, and neurocognition and neuropsychology. Exploratory meetings were held in 2021 in Europe and US culminating with a consensus meeting in Aarhus, Denmark in June 2023. Prior to this, eight groups addressed important areas in TS care: 1) diagnosis and genetics, 2) growth, 3) puberty and estrogen treatment, 4) cardiovascular health, 5) transition, 6) fertility assessment, monitoring, and counselling, 7) health surveillance for comorbidities throughout the lifespan, and 8) neurocognition and its implications for mental health and well-being. Each group produced proposals for the present guidelines, which were meticulously discussed by the entire group. Four pertinent questions were submitted for formal GRADE (Grading of Recommendations, Assessment, Development and Evaluation) evaluation with systematic review of the literature. The guidelines project was initiated by the European Society for Endocrinology and the Pediatric Endocrine Society, in collaboration with members from the European Society for Pediatric Endocrinology, the European Society of Human Reproduction and Embryology, the European Reference Network on Rare Endocrine Conditions, the Society for Endocrinology, and the European Society of Cardiology, Japanese Society for Pediatric Endocrinology, Australia and New Zealand Society for Pediatric Endocrinology and Diabetes, Latin American Society for Pediatric Endocrinology, Arab Society for Pediatric Endocrinology and Diabetes, and the Asia Pacific Pediatric Endocrine Society. Advocacy groups appointed representatives for pre-meeting discussions and the consensus meeting.
At the Third Turner Resource Network Symposium, a working group presented the results of collaborative discussions about the importance of autopsy in Turner syndrome (TS). Considerable gaps in ...understanding the causes of death in TS can only be closed by more frequent death investigations and autopsies. The presentation included an overview of autopsy methods, strategies for utilizing autopsy, and biobanking to address research questions about TS, and the role of palliative care in the context of autopsy. This review highlights strategies to promote autopsy and tissue donation, culminating with an action plan to increase autopsy rates in the TS community.
To address knowledge gaps about Turner syndrome (TS) associated disease mechanisms, the Turner Syndrome Society of the United States created the Turner Syndrome Research Registry (TSRR), a ...patient-powered registry for girls and women with TS. More than 600 participants, parents or guardians completed a 33-item foundational survey that included questions about demographics, medical conditions, psychological conditions, sexuality, hormonal therapy, patient and provider knowledge about TS, and patient satisfaction. The TSRR platform is engineered to allow individuals living with rare conditions and investigators to work side-by-side. The purpose of this article is to introduce the concept, architecture, and currently available content of the TSRR, in anticipation of inviting proposals to utilize registry resources.
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