Multidisciplinary Care for Moebius Syndrome and Related Disorders: Building a Management Protocol.

Moebius syndrome is a collection of orofacial anomalies with highly variable features affecting many different systems but characterised by bilateral facial palsy and absent eye abduction. We largely regard Moebius syndrome as a diagnosis of exclusion. Lack of awareness and knowledge means that children often fall between services, leading to treatment delays and difficulty interfacing with social care and schools, with long-term impact on physical health and psychosocial development.

Risdiplam in Spinal Muscular Atrophy: Safety Profile and Use Through The Early Access to Medicine Scheme for the Paediatric Cohort in Great Britain.

Background: Spinal muscular atrophy (SMA) is a progressive neuromuscular disease caused by mutations in Survival motor neuron 1 (SMN1) gene, leading to reduction in survival motor neuron protein (SMN), key for motor neuron survival and function in the brainstem and spinal cord. Risdiplam is an orally administered SMN2-splicing modifier which increases production of functional SMN protein. Risdiplam was offered in the UK under early access to medicines scheme (EAMS) to SMA type 1 and 2 patients aged 2 months and older, not suitable for authorised treatments from September 2020 to December 2021.

Safety and efficacy of tamoxifen in boys with Duchenne muscular dystrophy (TAMDMD): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.

Background: Drug repurposing could provide novel treatment options for Duchenne muscular dystrophy. Because tamoxifen-an oestrogen receptor regulator-reduced signs of muscular pathology in a Duchenne muscular dystrophy mouse model, we aimed to assess the safety and efficacy of tamoxifen in humans as an adjunct to corticosteroid therapy over a period of 48 weeks.

Methods: We did a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 12 study centres in seven European countries.

Communicating hydrocephalus and raised intracranial pressure in association with multi-systemic smooth muscle dysfunction syndrome (MSMDS).

Multi-systemic smooth muscle dysfunction syndrome (MSMDS) is extremely rare and can manifest in multiple ways. Associated hydrocephalus has not yet been reported. Here, we report a three-year-old girl with communicating hydrocephalus and raised intracranial pressure secondary to MSMDS.

Preventing Cardiomyopathy in DMD: A Randomized Placebo-Controlled Drug Trial.

Objective: To determine whether a combination of 2 heart medications would be tolerated and could prevent/delay the onset of cardiomyopathy in boys with Duchenne muscular dystrophy (DMD) compared with placebo.

Methods: This multicenter, parallel group, 1:1 patient randomized, placebo-controlled study of prophylactic perindopril and bisoprolol recruited boys with DMD aged 5-13 years, with normal ventricular function. Repeat assessments of left ventricular (LV) function, electrocardiogram, and adverse event reporting were performed 6 monthly.

Utility and safety of plasma exchange in paediatric neuroimmune disorders.

Aim: Our aim was to ascertain the indications, side effects, and outcomes in children receiving therapeutic plasma exchange (TPE) for neurological disorders.

Method: Medical records were retrospectively reviewed for 58 consecutive children (age ≤16y) undergoing 67 courses of TPE across four tertiary centres. Patient characteristics, treatment schedules, complications, and outcomes were analysed.

A Phase 1b Trial to Assess the Pharmacokinetics of Ezutromid in Pediatric Duchenne Muscular Dystrophy Patients on a Balanced Diet.

Ezutromid (SMT C1100) is a small-molecule utrophin modulator that was developed to treat Duchenne muscular dystrophy (DMD). Previous clinical trials of this agent revealed lower exposure in DMD patients compared with healthy volunteers, which may reflect differences in diet. This study evaluated the pharmacokinetics of ezutromid in patients with DMD who followed a balanced diet.

Randomised placebo-controlled trial of combination ACE inhibitor and beta-blocker therapy to prevent cardiomyopathy in children with Duchenne muscular dystrophy? (DMD Heart Protection Study): a protocol study.

Introduction: Although cardiologists were 'late-comers' to the multidisciplinary team-contributing to the complex care of patients with Duchenne muscular dystrophy (DMD), they now recognise the importance of systematic cardiac surveillance and timely therapy to prolonged survival in patients with DMD. Empirical deployment of cardioactive medications has already improved outcomes, but the evidence base for clinical decision making is weak. Fundamental questions remain as to whether prophylactic therapy is justified and convincingly superior to prompt deployment of the same therapies once left ventricular (LV) dysfunction is detected.

A checklist for clinical trials in rare disease: obstacles and anticipatory actions-lessons learned from the FOR-DMD trial.

Background: Trials in rare diseases have many challenges, among which are the need to set up multiple sites in different countries to achieve recruitment targets and the divergent landscape of clinical trial regulations in those countries. Over the past years, there have been initiatives to facilitate the process of international study set-up, but the fruits of these deliberations require time to be operationally in place. FOR-DMD (Finding the Optimum Steroid Regimen for Duchenne Muscular Dystrophy) is an academic-led clinical trial which aims to find the optimum steroid regimen for Duchenne muscular dystrophy, funded by the National Institutes of Health (NIH) for 5 years (July 2010 to June 2015), anticipating that all sites (40 across the USA, Canada, the UK, Germany and Italy) would be open to recruitment from July 2011.

Development of a consensus core dataset in juvenile dermatomyositis for clinical use to inform research.

Objectives: This study aimed to develop consensus on an internationally agreed dataset for juvenile dermatomyositis (JDM), designed for clinical use, to enhance collaborative research and allow integration of data between centres.

Methods: A prototype dataset was developed through a formal process that included analysing items within existing databases of patients with idiopathic inflammatory myopathies. This template was used to aid a structured multistage consensus process.

Safety, Tolerability, and Pharmacokinetics of SMT C1100, a 2-Arylbenzoxazole Utrophin Modulator, following Single- and Multiple-Dose Administration to Pediatric Patients with Duchenne Muscular Dystrophy.

Purpose: SMT C1100 is a utrophin modulator being evaluated as a treatment for Duchenne muscular dystrophy (DMD). This study, the first in pediatric DMD patients, reports the safety, tolerability and PK parameters of single and multiple doses of SMT C1100, as well as analyze potential biomarkers of muscle damage.

Methods: This multicenter, Phase 1 study enrolled 12 patients, divided equally into three groups (A-C).

Pain experience, expression and coping in boys and young men with Duchenne Muscular Dystrophy - A pilot study using mixed methods.

Unlabelled: There is limited research exploring the pain experience of boys and young men with Duchenne Muscular Dystrophy.

Methods: We conducted a mixed-methods pilot study to assess the feasibility of using particular measures of pain, pain coping and quality of life within semi-structured interviews with boys and young men with Duchenne Muscular Dystrophy and a postal survey of their parents. Non-probability, convenience sampling was used.

Novel compound heterozygous mutations in the desmoplakin gene cause hair shaft abnormalities and culminate in lethal cardiomyopathy.

A 2-month-old white girl born to nonconsanguineous parents presented to the dermatology department with hair loss that had commenced a few months after birth. Although her hair loss later stabilized, it remained sparse. By the age of 2 years, she was noted to have developed focal keratoderma over pressure points of the soles.

Phenytoin dosing and serum concentrations in paediatric patients requiring 20 mg/kg intravenous loading.

Introduction: Phenytoin has complex pharmacokinetics. The intravenous loading dose of phenytoin for children in status epilepticus has recently been increased from 18 to 20 mg/kg. There are no data on the clinical effectiveness and safety of this new dose.