Monique M Ryan

Publications (72)258.94 Total impact

• Article: Childhood Chronic Inflammatory Demyelinating Polyneuropathy: An Overview of 10 Cases in the Modern Era.

  Tyson L Ware, Andrew J Kornberg, M Victoria Rodriguez-Casero, Monique M Ryan
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  ABSTRACT: Chronic inflammatory demyelinating polyneuropathy is a rare condition in children. In this article, we report our experience in the management of 10 cases of childhood chronic inflammatory demyelinating polyneuropathy in a single center, in the era of contrast-enhanced magnetic resonance imaging (MRI), genetic microarray, and chronic inflammatory demyelinating polyneuropathy disease activity status. Robust neurophysiologic abnormalities were present in all cases and both MRI and lumbar puncture were useful adjuncts in diagnosis. Genetic microarray is a simple technique useful in excluding the most common hereditary demyelinating neuropathy. Intravenous immunoglobulin was an effective first-line therapy in most cases, with refractory cases responding to corticosteroids and rituximab. We found the chronic inflammatory demyelinating polyneuropathy disease activity status useful for assessing outcome at final follow-up, whereas the modified Rankin score was better for assessing peak motor disability.
  Journal of child neurology 01/2013; · 1.59 Impact Factor
• Article: A New Locus for X-linked Dominant Charcot Marie Tooth Disease (CMTX6) is Caused by Mutations in the Pyruvate Dehydrogenase Kinase Isoenzyme 3 (PDK3) Gene.

  Marina L Kennerson, Eppie M Yiu, David T Chuang, Aditi Kidambi, Shih-Chia Tso, Carolyn Ly, Rabia Chaudhry, Alexander P Drew, Gary Rance, Martin B Delatycki, Stephan Zuchner, Monique M Ryan, Garth A Nicholson
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  ABSTRACT: Hereditary motor and sensory disorders of the peripheral nerve form one of the most common groups of human genetic diseases collectively called Charcot-Marie-Tooth (CMT) neuropathy. Using linkage analysis in a three generation kindred we have mapped a new locus for X-linked dominant CMT to chromosome Xp22.11. A microsatellite scan of the X chromosome established significant linkage to several markers including DXS993 (Zmax=3.16; θ=0.05). Extended haplotype analysis refined the linkage region to a 1.43-Mb interval flanked by markers DXS7110 and DXS8027. Whole exome sequencing identified a missense mutation c.G473A (p.R158H) in the pyruvate dehydrogenase kinase isoenzyme 3 (PDK3) gene. The change localised within the 1.43-Mb linkage interval, segregated with the affected phenotype, and was excluded in ethnically matched control chromosomes. PDK3 is one of 4 isoenzymes regulating the pyruvate dehydrogenase complex (PDC), by reversible phosphorylation and is a nuclear-coded protein located in the mitochondrial matrix. PDC catalyzes the oxidative decarboxylation of pyruvate to acetyl CoA and is a key enzyme linking glycolysis to the energy-producing Krebs cycle and lipogenic pathways. We found that the R158H mutation confers enzyme hyperactivity and binds with stronger affinity than the wild-type to the inner-lipoyl (L2) domain of the E2p chain of PDC. Our findings suggest a reduced pyruvate flux due to R158H mutant PDK3-mediated hyper-phosphorylation of the PDC as the underlying pathogenic cause of peripheral neuropathy. The results highlight an important causative link between peripheral nerve degeneration and an essential bioenergetic or biosynthetic pathway required for the maintenance of peripheral nerves.
  Human Molecular Genetics 01/2013; · 7.64 Impact Factor
• Article: Pontocerebellar hypoplasia type 1: Clinical spectrum and relevance of EXOSC3 mutations.

  Sabine Rudnik-Schöneborn, Jan Senderek, Joanna C Jen, Gunnar Houge, Pavel Seeman, Alena Puchmajerová, Luitgard Graul-Neumann, Ulrich Seidel, Rudolf Korinthenberg, Janbernd Kirschner, [......], Knut Brockmann, Lionel Van Maldergem, Manuel Schiff, Andreas Holzinger, Peter Barth, William Reardon, Michael Yourshaw, Stanley F Nelson, Thomas Eggermann, Klaus Zerres
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  ABSTRACT: OBJECTIVES: Pontocerebellar hypoplasia with spinal muscular atrophy, also known as PCH1, is a group of autosomal recessive disorders characterized by generalized muscle weakness and global developmental delay commonly resulting in early death. Gene defects had been discovered only in single patients until the recent identification of EXOSC3 mutations in several families with relatively mild course of PCH1. We aim to genetically stratify subjects in a large and well-defined cohort to define the clinical spectrum and genotype-phenotype correlation. METHODS: We documented clinical, neuroimaging, and morphologic data of 37 subjects from 27 families with PCH1. EXOSC3 gene sequencing was performed in 27 unrelated index patients of mixed ethnicity. RESULTS: Biallelic mutations in EXOSC3 were detected in 10 of 27 families (37%). The most common mutation among all ethnic groups was c.395A>C, p.D132A, responsible for 11 (55%) of the 20 mutated alleles and ancestral in origin. The mutation-positive subjects typically presented with normal pregnancy, normal birth measurements, and relative preservation of brainstem and cortical structures. Psychomotor retardation was profound in all patients but lifespan was variable, with 3 subjects surviving beyond the late teens. Abnormal oculomotor function was commonly observed in patients surviving beyond the first year. Major clinical features previously reported in PCH1, including intrauterine abnormalities, postnatal hypoventilation and feeding difficulties, joint contractures, and neonatal death, were rarely observed in mutation-positive infants but were typical among the mutation-negative subjects. CONCLUSION: EXOSC3 mutations account for 30%-40% of patients with PCH1 with variability in survival and clinical severity that is correlated with the genotype.
  Neurology 01/2013; · 8.31 Impact Factor
• Article: Venlafaxine ingestion in a 4-year-old girl.

  Tyson L Ware, Kate McCloskey, Monique M Ryan, Noel Cranswick
  Journal of Paediatrics and Child Health 11/2012; 48(11):1047-8. · 1.28 Impact Factor
• Article: Juvenile Parkinsonism.

  Tyson L Ware, Jayasri Srinivasan, Linda Gonzalez, Winita Hardikar, Adam M Scheinberg, Louise Baker, Chidambaram Prakash, Monique M Ryan
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  ABSTRACT: We present the case of a 14-year-old boy presented with a recent history of progressive neurologic decline and extrapyramidal features. The history and findings with illustrative figures are detailed, and a diagnostic approach to the presentation is considered. The therapeutic options and broader management issues are briefly reviewed.
  Journal of Paediatrics and Child Health 09/2012; · 1.28 Impact Factor
• Article: Binaural speech processing in individuals with auditory neuropathy.

  G Rance, M M Ryan, P Carew, L A Corben, E Yiu, J Tan, M B Delatycki
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  ABSTRACT: Auditory neuropathy disrupts the neural representation of sound and may therefore impair processes contingent upon inter-aural integration. The aims of this study were to investigate binaural auditory processing in individuals with axonal (Friedreich ataxia) and demyelinating (Charcot-Marie-Tooth disease type 1A) auditory neuropathy and to evaluate the relationship between the degree of auditory deficit and overall clinical severity in patients with neuropathic disorders. Twenty-three subjects with genetically confirmed Friedreich ataxia and 12 subjects with Charcot-Marie-Tooth disease type 1A underwent psychophysical evaluation of basic auditory processing (intensity discrimination/temporal resolution) and binaural speech perception assessment using the Listening in Spatialized Noise test. Age, gender and hearing-level-matched controls were also tested. Speech perception in noise for individuals with auditory neuropathy was abnormal for each listening condition, but was particularly affected in circumstances where binaural processing might have improved perception through spatial segregation. Ability to use spatial cues was correlated with temporal resolution suggesting that the binaural-processing deficit was the result of disordered representation of timing cues in the left and right auditory nerves. Spatial processing was also related to overall disease severity (as measured by the Friedreich Ataxia Rating Scale and Charcot-Marie-Tooth Neuropathy Score) suggesting that the degree of neural dysfunction in the auditory system accurately reflects generalized neuropathic changes. Measures of binaural speech processing show promise for application in the neurology clinic. In individuals with auditory neuropathy due to both axonal and demyelinating mechanisms the assessment provides a measure of functional hearing ability, a biomarker capable of tracking the natural history of progressive disease and a potential means of evaluating the effectiveness of interventions.
  Neuroscience 09/2012; 226C:227-235. · 3.38 Impact Factor
• Article: Genetic axonal neuropathies and neuronopathies of pre-natal and infantile onset.

  Eppie M Yiu, Monique M Ryan
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  ABSTRACT: The infantile-onset axonal neuropathies and neuronopathies are an uncommon and heterogeneous group of conditions causing weakness, wasting, and developmental delay in early childhood. Many are associated with central nervous system or other systemic manifestations and cause early mortality. We review the axonal Charcot-Marie-Tooth subtypes with onset in infancy, spinal muscular atrophy, and related syndromes of early infancy, giant axonal neuropathy, infantile neuroaxonal dystrophy, hereditary motor and sensory neuropathy with agenesis of the corpus callosum, early-onset neuropathies associated with mitochondrial disorders, and other less well-delineated clinical entities. Useful clinical and neuropathologic features in the diagnostic work-up of these conditions are also presented.
  Journal of the Peripheral Nervous System 09/2012; 17(3):285-300. · 2.80 Impact Factor
• Article: A family with 2 X-linked disorders: Charcot-Marie-Tooth disease and hemophilia A.

  Nortina Shahrizaila, Khean Jin Goh, Azlina Ahmad-Annuar, Rabia Chaudhry, Carolyn Ly, Monique M Ryan, Garth Nicholson, Marina Kennerson
  Muscle & Nerve 09/2012; 46(3):454-5. · 2.37 Impact Factor
• Article: Mutations in the RNA exosome component gene EXOSC3 cause pontocerebellar hypoplasia and spinal motor neuron degeneration

  Jijun Wan, Michael Yourshaw, Hafsa Mamsa, Sabine, Manoj P Menezes, Ji Eun Hong, Derek W Leong, Jan Senderek, Michael S Salman, David Chitayat, [......], Masafumi Sanefuji, Perry B Shieh, Noriko Salamon, Ronald C Kim, Harry V Vinters, Zugen Chen, Klaus Zerres, Monique M Ryan, Stanley F Nelson, Joanna C Jen
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  ABSTRACT: RNA exosomes are multi-subunit complexes conserved throughout evolution and are emerging as the major cellular machinery for processing, surveillance and turnover of a diverse spectrum of coding and noncoding RNA substrates essential for viability. By exome sequencing, we discovered recessive mutations in EXOSC3 (encoding exosome component 3) in four siblings with infantile spinal motor neuron disease, cerebellar atrophy, progressive microcephaly and profound global developmental delay, consistent with pontocerebellar hypoplasia type 1 (PCH1; MIM 607596). We identified mutations in EXOSC3 in an additional 8 of 12 families with PCH1. Morpholino knockdown of exosc3 in zebrafish embryos caused embryonic maldevelopment, resulting in small brain size and poor motility, reminiscent of human clinical features, and these defects were largely rescued by co-injection with wild-type but not mutant exosc3 mRNA. These findings represent the first example of an RNA exosome core component gene that is responsible for a human disease and further implicate dysregulation of RNA processing in cerebellar and spinal motor neuron maldevelopment and degeneration.
  Nature Genetics 04/2012; 44(6):704-708. · 35.53 Impact Factor
• Article: Auditory function in children with Charcot-Marie-Tooth disease.

  Gary Rance, Monique M Ryan, Kristen Bayliss, Kathryn Gill, Caitlin O'Sullivan, Marny Whitechurch
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  ABSTRACT: The peripheral manifestations of the inherited neuropathies are increasingly well characterized, but their effects upon cranial nerve function are not well understood. Hearing loss is recognized in a minority of children with this condition, but has not previously been systemically studied. A clear understanding of the prevalence and degree of auditory difficulties in this population is important as hearing impairment can impact upon speech/language development, social interaction ability and educational progress. The aim of this study was to investigate auditory pathway function, speech perception ability and everyday listening and communication in a group of school-aged children with inherited neuropathies. Twenty-six children with Charcot-Marie-Tooth disease confirmed by genetic testing and physical examination participated. Eighteen had demyelinating neuropathies (Charcot-Marie-Tooth type 1) and eight had the axonal form (Charcot-Marie-Tooth type 2). While each subject had normal or near-normal sound detection, individuals in both disease groups showed electrophysiological evidence of auditory neuropathy with delayed or low amplitude auditory brainstem responses. Auditory perception was also affected, with >60% of subjects with Charcot-Marie-Tooth type 1 and >85% of Charcot-Marie-Tooth type 2 suffering impaired processing of auditory temporal (timing) cues and/or abnormal speech understanding in everyday listening conditions.
  Brain 04/2012; 135(Pt 5):1412-22. · 9.46 Impact Factor
• Article: Demyelinating prenatal and infantile developmental neuropathies.

  Eppie M Yiu, Monique M Ryan
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  ABSTRACT: The prenatal and infantile neuropathies are an uncommon and complex group of conditions, most of which are genetic. Despite advances in diagnostic techniques, approximately half of children presenting in infancy remain without a specific diagnosis. This review focuses on inherited demyelinating neuropathies presenting in the first year of life. We clarify the nomenclature used in these disorders, review the clinical features of demyelinating forms of Charcot-Marie-Tooth disease with early onset, and discuss the demyelinating infantile neuropathies associated with central nervous system involvement. Useful clinical, neurophysiologic, and neuropathologic features in the diagnostic work-up of these conditions are also presented.
  Journal of the Peripheral Nervous System 03/2012; 17(1):32-52. · 2.80 Impact Factor
• Article: Muscle cramp in pediatric Charcot-Marie-Tooth disease type 1A: prevalence and predictors.

  Fiona Blyton, Monique M Ryan, Robert A Ouvrier, Joshua Burns
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  ABSTRACT: To identify correlates of calf cramp in children with Charcot-Marie-Tooth disease type 1A (CMT1A). Throughout Australia, 81 children aged 2-16 years with CMT1A were recruited. Measures of strength, ankle range, foot posture, balance, agility, endurance, gait, and neurophysiology were collected. Post hoc logistic regression analyses were performed to identify independent predictors of calf cramp. Of the 81 children, 26 (32%) reported calf cramp, and 1 child each reported toe, quadriceps, or arm cramp. Calf cramp was associated (p < 0.05) with older age; the presence of hand tremor; stronger foot inversion, eversion, dorsiflexion, and plantarflexion; and better performance in long-jump and 9-hole peg tests. Logistic regression analysis revealed only increasing age (odds ratio [OR] 1.32, 95% confidence interval [CI] 1.11-1.58; p = 0.002) and the presence of hand tremor (OR 3.81, 95% CI 1.18-12.56; p = 0.028) as independent predictors of calf cramp. Calf cramps are common in children with CMT1A and worsen with age. This study revealed a previously unrecognized link between cramp and hand tremor in children with CMT1A. Further investigation of proposed mechanisms and risk factors common to both cramp and tremor will contribute to our understanding of these common complications of CMT1A.
  Neurology 11/2011; 77(24):2115-8. · 8.31 Impact Factor
• Article: Autoimmune myasthenia gravis, immunotherapy and thymectomy in children.

  Tyson L Ware, Monique M Ryan, Andrew J Kornberg
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  ABSTRACT: Autoimmune myasthenia gravis is a rare condition in children. Identifying antibodies directed against the acetylcholine receptor is helpful in making the diagnosis. However, seronegative cases do exist and need to be distinguished from congenital forms of myasthenia. There is little published experience to inform the judicious management of autoimmune myasthenia gravis in children. In this article, we report our experience in the management of 12 cases of autoimmune myasthenia gravis in children in the modern era of medical immunotherapy and thymectomy.
  Neuromuscular Disorders 09/2011; 22(2):118-21. · 2.80 Impact Factor
• Article: Extended treatment of childhood Charcot-Marie-Tooth disease with high-dose ascorbic acid.

  Joshua Burns, Robert A Ouvrier, Eppie M Yiu, Monique M Ryan
  Journal of the Peripheral Nervous System 09/2011; 16(3):272-4. · 2.80 Impact Factor
• Source

  Available from: Alfred Klausegger

  Article: Epidermolysis bullosa with late-onset muscular dystrophy and plectin deficiency.

  Eppie M Yiu, Alfred Klausegger, Leigh B Waddell, Nikolaus Grasern, Lyn Lloyd, Kim Tran, Kathryn N North, Johann W Bauer, Penelope McKelvie, C W Chow, Monique M Ryan, Dedee F Murrell
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  ABSTRACT: Epidermolysis bullosa associated with muscular dystrophy is a rare, autosomal recessive form of epidermolysis bullosa simplex caused by mutations in the plectin gene, PLEC1. We describe a phenotypically mild case due to compound heterozygous mutations in PLEC1 (2677_2685del and the novel mutation Q1644X). Clinical features included mild skin blistering since birth, slowly progressive and late-onset upper limb-predominant weakness, facial weakness, ptosis, incomplete ophthalmoplegia, and paroxysmal atrial fibrillation.
  Muscle & Nerve 07/2011; 44(1):135-41. · 2.37 Impact Factor
• Article: Health status of boys with Duchenne muscular dystrophy: a parent's perspective.

  Paula Bray, Anita C Bundy, Monique M Ryan, Kathryn N North, Joshua Burns
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  ABSTRACT: To investigate parent-reported health status of boys with Duchenne muscular dystrophy (DMD) compared with a large Australian normative population and a cohort of children with Charcot-Marie-Tooth disease type 1A (CMT1A). The Child Health Questionnaire parent form (CHQ-PF50) was completed by parents of 34 boys with confirmed DMD. Seventeen parents were followed up at 6 months. CHQ-PF50 data were compared with 2620 age-matched norms and 90 children with CMT1A. All domains of the CHQ-PF50 for the DMD cohort were significantly lower than the general paediatric population, particularly for physical functioning (t = -17.2, P < 0.001) and the child's ability to fulfil school and social roles because of physical limitations (t = -9.4, P < 0.001). Parents experienced greatest emotional impact of their child's DMD around the time of loss of ambulation. Children with DMD had lower health status compared with children with CMT1A with the exception of the behaviour and pain domains. Physical functioning worsened during 6 months (P = 0.04); no other changes in health status were observed at follow-up. Parents report the impact of DMD on health status to be considerably worse when compared with CMT1A. Interventions should target minimising the impact of physical limitations on role functioning.
  Journal of Paediatrics and Child Health 03/2011; 47(8):557-62. · 1.28 Impact Factor
• Article: Spontaneous intracranial hypotension in childhood: a case report and review of the literature.

  Eunice K Chan, Bernard Yan, Monique M Ryan
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  ABSTRACT: Spontaneous intracranial hypotension results from 1 or more spontaneous spinal cerebrospinal fluid leaks, and generally presents with severe and persisting orthostatic headache. Diagnosis can be difficult as spontaneous intracranial hypotension is very rare in childhood and has a wide spectrum of clinical features and neuroimaging findings. Lumbar autologous epidural blood patch can be helpful for confirmation of diagnosis and symptom relief. We report a 15-year-old female with spontaneous intracranial hypotension who experienced immediate resolution of her symptoms following lumbar autologous epidural blood patch on 2 occasions, and review the literature on this well-recognized but probably underdiagnosed headache syndrome in childhood.
  Journal of child neurology 02/2011; 26(6):761-6. · 1.59 Impact Factor
• Article: Pediatric sciatic neuropathy associated with neoplasms.

  Hugh J McMillan, Jayashri Srinivasan, Basil T Darras, Monique M Ryan, James Davis, Hart G Lidov, Deepak Gill, H Royden Jones
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  ABSTRACT: Seven children with sciatic neuropathy associated with an underlying neoplasm are reported. Clinical presentation, electrophysiological data, imaging, pathology, and/or autopsy results are described. Pain and weakness, primarily foot drop, were the most common presenting symptoms. The mechanism of sciatic neuropathy was varied and included: nerve infiltration by the adjacent neoplasm (neuroblastoma, rhabdomyosarcoma, and leukemic or lymphomatous infiltration); an expanding, intrinsic neurogenic tumor (perineurioma); or intraoperative stretch injury (osteosarcoma resection). The prognosis for sciatic nerve recovery was good among children who survived their associated cancer. Three children died from the cancer or complications of treatment. One child with perineurioma remained clinically stable, and two children improved after treatment of their neoplasm.
  Muscle & Nerve 02/2011; 43(2):183-8. · 2.37 Impact Factor
• Article: Neurophysiologic findings in children presenting with pes cavus.

  Ahmad R Mohamed, M Victoria Rodriguez-Casero, Andrew J Kornberg, Monique M Ryan
  Journal of the Peripheral Nervous System 09/2010; 15(3):238-40. · 2.80 Impact Factor
• Article: Atypical Silver-Russell phenotype resulting from maternal uniparental disomy of chromosome 7.

  Zornitza Stark, Monique M Ryan, Damien L Bruno, Trent Burgess, Ravi Savarirayan
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  ABSTRACT: We report on a patient with atypical Silver-Russell phenotype comprising severe growth retardation, unusual facies, bilateral Duane anomaly and infantile hypercalcemia caused by maternal uniparental iso/heterodisomy (mUPD) of chromosome 7. The development of myoclonus in this patient lends further support to the hypothesis that abnormal imprinting of the SGCE gene is responsible for some cases of myoclonus-dystonia syndrome. This case highlights the utility of SNP microarray technology as an accessible tool for the diagnosis of mUPD7 in atypical cases. We propose that depending on the balance of iso- and heterodisomic segments in a particular patient, mUPD7 may result in a range of phenotypes not confined to classic Silver-Russell syndrome.
  American Journal of Medical Genetics Part A 09/2010; 152A(9):2342-5. · 2.39 Impact Factor