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Dive into the research topics where Robert McWilliam is active.

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Featured researches published by Robert McWilliam.


Annals of Neurology | 2000

Clinical, genetic, and expression studies of mutations in the potassium channel gene KCNA1 reveal new phenotypic variability.

Louise H Eunson; Ruth Rea; Sameer M. Zuberi; S. Youroukos; C. P. Panayiotopoulos; R. Liguori; P. Avoni; Robert McWilliam; John Stephenson; Michael G. Hanna; Dimitri M. Kullmann; A Spauschus

Episodic ataxia type 1 (EA1) is an autosomal dominant central nervous system potassium channelopathy characterized by brief attacks of cerebellar ataxia and continuous interictal myokymia. Point mutations in the voltage‐gated potassium channel gene KCNA1 on chromosome 12p associate with EA1. We have studied 4 families and identified three new and one previously reported heterozygous point mutations in this gene. Affected members in Family A (KCNA1 G724C) exhibit partial epilepsy and myokymia but no ataxic episodes, supporting the suggestion that there is an association between mutations of KCNA1 and epilepsy. Affected members in Family B (KCNA1 C731A) exhibit myokymia alone, suggesting a new phenotype of isolated myokymia. Family C harbors the first truncation to be reported in KCNA1 (C1249T) and exhibits remarkably drug‐resistant EA1. Affected members in Family D (KCNA1 G1210A) exhibit attacks typical of EA1. This mutation has recently been reported in an apparently unrelated family, although no functional studies were attempted. Heterologous expression of the proteins encoded by the mutant KCNA1 genes suggest that the four point mutations impair delayed‐rectifier type potassium currents by different mechanisms. Increased neuronal excitability is likely to be the common pathophysiological basis for the disease in these families. The degree and nature of the potassium channel dysfunction may be relevant to the new phenotypic observations reported in this study. Ann Neurol 2000;48:647–656


Annals of Neurology | 2008

Brain involvement in muscular dystrophies with defective dystroglycan glycosylation

Emma Clement; Eugenio Mercuri; Caroline Godfrey; Janine Smith; S. Robb; Maria Kinali; Volker Straub; Kate Bushby; Adnan Y. Manzur; Beril Talim; Frances Cowan; R. Quinlivan; Andrea Klein; Cheryl Longman; Robert McWilliam; Haluk Topaloglu; Rachael Mein; Stephen Abbs; Kathryn N. North; A. James Barkovich; Mary A. Rutherford; Francesco Muntoni

To assess the range and severity of brain involvement, as assessed by magnetic resonance imaging, in 27 patients with mutations in POMT1 (4), POMT2 (9), POMGnT1 (7), Fukutin (4), or LARGE (3), responsible for muscular dystrophies with abnormal glycosylation of dystroglycan (dystroglycanopathies).


American Journal of Medical Genetics Part A | 2008

Extreme phenotypic diversity and nonpenetrance in families with the LMNA gene mutation R644C

Julia Rankin; Michaela Auer-Grumbach; Warwick Bagg; Kevin Colclough; Nguyen Thuy Duong; Jane Fenton-May; Andrew T. Hattersley; Judith Hudson; Philip Jardine; Dragana Josifova; Cheryl Longman; Robert McWilliam; Katharine R. Owen; M. Walker; Manfred Wehnert; Sian Ellard

Mutations in the LMNA gene result in diverse phenotypes including Emery Dreifuss muscular dystrophy, limb girdle muscular dystrophy, dilated cardiomyopathy with conduction system disease, Dunnigan type familial partial lipodystrophy, mandibulo acral dysplasia, Hutchinson Gilford progeria syndrome, restrictive dermopathy and autosomal recessive Charcot Marie Tooth type 2. The c.1930C > T (R644C) missense mutation has previously been reported in eight unrelated patients with variable features including left ventricular hypertrophy, limb girdle muscle weakness, dilated cardiomyopathy and atypical progeria. Here we report on the details of nine additional patients in eight families with this mutation. Patients 1 and 2 presented with lipodystrophy and insulin resistance, Patient 1 having in addition focal segmental glomerulosclerosis. Patient 3 presented with motor neuropathy, Patient 4 with arthrogryposis and dilated cardiomyopathy with left ventricular non‐compaction, Patient 5 with severe scoliosis and contractures, Patient 6 with limb girdle weakness and Patient 7 with hepatic steatosis and insulin resistance. Patients 8 and 9 are brothers with proximal weakness and contractures. Nonpenetrance was observed frequently in first degree relatives. This report provides further evidence of the extreme phenotypic diversity and low penetrance associated with the R644C mutation. Possible explanations for these observations are discussed.


Brain | 2014

Epilepsy due to PNPO mutations: genotype, environment and treatment affect presentation and outcome

Philippa B. Mills; Stephane Camuzeaux; Emma Footitt; Kevin Mills; Paul Gissen; Laura Fisher; Krishna B. Das; Sophia Varadkar; Sameer M. Zuberi; Robert McWilliam; Tommy Stödberg; Barbara Plecko; Matthias R. Baumgartner; Oliver Maier; Sophie Calvert; Kate Riney; Nicole I. Wolf; John H. Livingston; Pronab Bala; Chantal Morel; François Feillet; Francesco Raimondi; Ennio Del Giudice; W. Kling Chong; Matthew Pitt; Peter Clayton

Mutations in PNPO are a known cause of neonatal onset seizures that are resistant to pyridoxine but responsive to pyridoxal phosphate (PLP). Mills et al. show that PNPO mutations can also cause neonatal onset seizures that respond to pyridoxine but worsen with PLP, as well as PLP-responsive infantile spasms.


Neuromuscular Disorders | 1999

Muscle ultrasound in the assessment of suspected neuromuscular disease in childhood

S.M. Zuberi; N Matta; S Nawaz; J.B.P Stephenson; Robert McWilliam; A Hollman

One hundred paediatric, muscle ultrasound examinations performed in the evaluation of suspected neuromuscular disease were reviewed. The results were related to the presence or absence of neuromuscular disease in each child assessed. The group comprised 66 males and 34 females, age range 2 months to 16 years (mean 5.3 years). Scans were graded I-IV, according to muscle echogenicity, using Heckmatts criteria. Thirty-two children had a final diagnosis of neuromuscular disease. The sensitivity of ultrasound in detecting neuromuscular disease was 78% with 91% specificity. The test was more reliable in the sub-group of > 3 years with a sensitivity of 81% and specificity of 96%. There was a significant difference in disease status, (with and without neuromuscular disease), between children with a normal, grade I, scan and those with an abnormal, grade II, III, IV, image (chi-square, P < 0.001, 95% confidence limits 0.54-0.86). Muscle ultrasound is a specific and sensitive investigation for suspected neuromuscular disease in children.


European Journal of Paediatric Neurology | 2010

Pyruvate dehydrogenase E2 deficiency: A potentially treatable cause of episodic dystonia

Catherine McWilliam; Cheryl K. Ridout; Ruth M. Brown; Robert McWilliam; John Tolmie; Garry K. Brown

The association of progressive episodic dystonia and learning disability with distinctive neuroimaging findings may lead to consideration of atypical Pantothenate Kinase Associated Neurodegeneration (PKAN) and investigations directed towards that diagnosis. Recent reports indicate that deficiency of dihydrolipoamide acetyltransferase, the E2 component of the pyruvate dehydrogenase complex, may present similarly, and that this disorder should also be considered in the differential diagnosis. We describe two sisters with early onset episodic dystonia and pyruvate dehydrogenase deficiency caused by defects in the E2 subunit. Both have neuroimaging features similar to previously described patients and have mutations in the DLAT gene. As this condition is potentially treatable with a ketogenic diet, the possibility of this diagnosis should be considered in similar cases.


Neuromuscular Disorders | 2014

Congenital myopathies with secondary neuromuscular transmission defects; A case report and review of the literature

Pedro M. Rodríguez Cruz; C. Sewry; David Beeson; Sandeep Jayawant; Waney Squier; Robert McWilliam; Jacqueline Palace

Congenital myopathies are a clinically and genetically heterogeneous group of disorders characterized by early onset hypotonia, weakness and characteristic, but not pathognomonic, structural abnormalities in muscle fibres. The clinical features overlap with muscular dystrophies, myofibrillar myopathies, neurogenic conditions and congenital myasthenic syndromes. We describe a case of cap myopathy with myasthenic features due to a mutation in the TPM2 gene that responded to anticholinesterase therapy. We also review other published cases of congenital myopathies with neuromuscular transmission abnormalities. This report expands the spectrum of congenital myopathies with secondary neuromuscular transmission defects. The recognition of these cases is important since these conditions can benefit from treatment with drugs enhancing neuromuscular transmission.


Brain Injury | 2011

Health-related quality-of-life and behavioural outcome in survivors of childhood meningitis.

Ruth E. Sumpter; Andreas Brunklaus; Robert McWilliam; Liam Dorris

Objective: To describe behavioural and health-related quality-of-life (HRQoL) outcomes in survivors of childhood meningitis and identify variables predictive of psychosocial outcome. Methods: Psychosocial outcomes were measured via parent and teacher report using the Strengths and Difficulties Questionnaire (SDQ) and the Paediatric Quality of Life Inventory (PedsQL Core & Fatigue versions). Participants were 334 consecutive survivors admitted to a regional childrens hospital (1991–2007). One hundred and twelve of 346 (34%) returned postal questionnaires and file review confirmed diagnosis in 100 cases. Results: At a mean of 8 years post-illness 32% of parents and 19% of teachers reported clinically significant behavioural difficulties on the SDQ; along with significantly lowered HRQoL on PedsQL measures. Later sequelae such as learning disability and hearing/visual impairment, along with socioeconomic status, independently predicted behavioural and HRQoL outcome on regression analysis. Acute disease complications were associated with later occurrence of epilepsy, learning disability and visual impairment, but not directly with psychosocial outcomes at time of follow-up. Conclusions: Survivors with these sequelae should be screened for emotional and behavioural difficulties during key developmental transitions such as school entry. These findings strongly support recent UK clinical guidelines (NICE and SIGN) proposing that parents be made aware of possible psychological complications on discharge.


Developmental Medicine & Child Neurology | 2000

Reduced accommodative function in dyskinetic cerebral palsy: a novel management strategy

Linda M Ross; Gordon Heron; Roisin Mackie; Robert McWilliam; Gordon N. Dutton

A9‐year‐old boy with dyskinetic cerebral palsy secondary to neonatal encephalopathy is described. He presented with blurring of near vision which had begun to impact on his school work. Objective assessment of accommodation showed that very little was present, although convergence was almost normal. The near‐vision symptoms were completely removed and reading dramatically improved with the provision of varifocal spectacles. Varifocal lenses provide an optimal correction for far, intermediate (i.e. for computer screens), and near distances (i.e. for reading). Managing this type of patient with varifocal spectacles has not been previously reported. It is clearly very important to prescribe an optimal spectacle correction to provide clear vision to optimize learning.


Technology and Health Care | 2012

A combination of Botulinum Toxin A therapy and Functional Electrical Stimulation in children with cerebral palsy --A pilot study

Sujay Galen; Laura Wiggins; Robert McWilliam; Malcolm H. Granat

BACKGROUND Among the ambulant population of children with spastic cerebral palsy (CP), dynamic equinus is one of the most common form of gait deviation that is encountered. OBJECTIVE To investigate the combined effects of Functional Electrical Stimulation (FES) and Botulinum Toxin A (BTXA) therapy in children with spastic CP, and to demonstrate the feasibility of this combination therapy. METHODS A single-subject design with repeated measures was adopted. Eight children (six males, two females; mean age 7 y 9 mo, SD 1 y 5 mo; range 7 y to 11 y) diagnosed with hemiplegic (n=6) or diplegic (n=2) spastic CP completed the study. Each subject participated in the study for twenty weeks. This period consisted of baseline (one week), BTXA phase (three weeks), first FES phase (four weeks), first control phase (four weeks), second FES phase (four weeks) and second control phase (four weeks). Subjects were assessed at the end of each phase. The ankle angle at the end of swing phase was selected as the primary outcome measure. The secondary outcome measure recorded was the foot contact pattern. RESULTS There was an increase in ankle dorsiflexion at the end of the combined intervention in most subjects (n=6), accompanied by an improvement in foot contact pattern. CONCLUSIONS This pilot study demonstrated that it is feasible to combine BTXA therapy with FES in ambulant children with spastic CP.

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Cheryl Longman

Southern General Hospital

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John Tolmie

Royal Hospital for Sick Children

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A Spauschus

University College London

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John B.P. Stephenson

Royal Hospital for Sick Children

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Louise H Eunson

University College London

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Aline Russell

Southern General Hospital

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J Tolmie

Southern General Hospital

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John Stephenson

University of Huddersfield

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