Ophthalmic features of<i>PLA2G6</i>-related paediatric neurodegeneration with brain iron accumulation

Khan, Arif O.; AlDrees, Abdulmajeed; Elmalik, Salah A.; Hassan, Hamdy H.; Kœnig, M.; Stevanin, Giovanni; Azzedine, Hamid; Salih, Mustafa A.

doi:10.1136/bjophthalmol-2013-304527

Cited by 14 publications

(8 citation statements)

References 10 publications

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“…Moreover, these mutations are associated with hypothyroidism, schizophrenia, diabetes and other diseases (11–13). On magnetic resonance images, most patients carrying the PLA2G6 mutation showed an iron accumulation in the globus pallidus and/or the substantia nigra in T2-weighted images (13, 14). In pathological examinations of individuals with the PLA2G6 mutation, abnormal α-synuclein proteins and hyperphosphorylation of tau proteins were found, and may progress to become Lewy bodies (LBs), neurofibrillary tangles and neuropil threads (15, 16).…”

Section: The Clinical Phenotypes Of Pla2g6-associated Neurodegenerationmentioning

confidence: 99%

PLA2G6-Associated Neurodegeneration (PLAN): Review of Clinical Phenotypes and Genotypes

2018

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Phospholipase A2 group VI (PLA2G6)-associated neurodegeneration (PLAN) includes a series of neurodegenerative diseases that result from the mutations in PLA2G6. PLAN has genetic and clinical heterogeneity, with different mutation sites, mutation types and ethnicities and its clinical phenotype is different. The clinical phenotypes and genotypes of PLAN are closely intertwined and vary widely. PLA2G6 encodes a group of VIA calcium-independent phospholipase A2 proteins (iPLA2β), an enzyme involved in lipid metabolism. According to the age of onset and progressive clinical features, PLAN can be classified into the following subtypes: infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (ANAD) and parkinsonian syndrome which contains adult onset dystonia parkinsonism (DP) and autosomal recessive early-onset parkinsonism (AREP). In this review, we present an overview of PLA2G6-associated neurodegeneration in the context of current research.

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Section: The Clinical Phenotypes Of Pla2g6-associated Neurodegenerationmentioning

confidence: 99%

PLA2G6-Associated Neurodegeneration (PLAN): Review of Clinical Phenotypes and Genotypes

2018

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“…Eye movement abnormalities include hypometric and slow vertical saccades, normal horizontal saccades, saccadic pursuit, impaired vestibulo-ocular reflex suppression, poor convergence, square-wave jerk saccadic intrusions, and abnormal vertical optokinetic reflex ( 64 ). Patients with PLA2G6 mutations (#603604) can present with up gaze palsy, poor convergence, saccadic intrusions, and saccadic pursuit ( 65 ).…”

Section: Introductionmentioning

confidence: 99%

Eye Movements in Parkinson’s Disease and Inherited Parkinsonian Syndromes

Pretegiani

Optican

2017

Front. Neurol.

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Despite extensive research, the functions of the basal ganglia (BG) in movement control have not been fully understood. Eye movements, particularly saccades, are convenient indicators of BG function. Here, we review the main oculomotor findings reported in Parkinson’s disease (PD) and genetic parkinsonian syndromes. PD is a progressive, neurodegenerative disorder caused by dopaminergic cell loss within the substantia nigra pars compacta, resulting in depletion of striatal dopamine and subsequent increased inhibitory BG output from the internal globus pallidus and the substantia nigra pars reticulata. Eye movement abnormalities are common in PD: anomalies are more evident in voluntary than reflexive saccades in the initial stages, but visually guided saccades may also be involved at later stages. Saccadic hypometria (including abnormally fragmented saccades), reduced accuracy, and increased latency are among the most prominent deficits. PD patients show also unusually frequent and large square wave jerks and impaired inhibition of reflexive saccades when voluntary mirror saccades are required. Poor convergence ability and altered pursuit are common. Inherited parkinsonisms are a heterogeneous group of rare syndromes due to gene mutations causing symptoms resembling those of PD. Eye movement characteristics of some parkinsonisms have been studied. While sharing some PD features, each syndrome has a distinctive profile that could contribute to better define the clinical phenotype of parkinsonian disorders. Moreover, because the pathogenesis and the underlying neural circuit failure of inherited parkinsonisms are often well defined, they might offer a better prospect than idiopathic PD to understand the BG function.

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“…Ophthalmic features include strabismus, up‐gaze palsy, impaired pursuit with saccadic intrusions, and pendular nystagmus. Vestibulo‐ocular responses are not impaired . A case of oculogyric crisis induced by levodopa has been described in a patient with adult‐onset dystonia‐parkinsonism .…”

Section: Inborn Errors Of Metabolism Associated With Ocular Motor Dismentioning

confidence: 99%

“…21 Adult-onset dystonia-parkinsonism (NBIA type 2) also belongs to the heterogeneous group of degenerative Vestibulo-ocular responses are not impaired. 64 A case of oculogyric crisis induced by levodopa has been described in a patient with adult-onset dystonia-parkinsonism. 65 Only symptomatic treatment is available.…”

Section: Disorders Of Mineral Metal or Vitamin Metabolismmentioning

confidence: 99%

Eye movement disorders and neurological symptoms in late‐onset inborn errors of metabolism

et al. 2018

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Inborn errors of metabolism in adults are still largely unexplored. Despite the fact that adult‐onset phenotypes have been known for many years, little attention is given to these disorders in neurological practice. The adult‐onset presentation differs from childhood‐onset phenotypes, often leading to considerable diagnostic delay. The identification of these patients at the earliest stage of disease is important, given that early treatment may prevent or lessen further brain damage. Neurological and psychiatric symptoms occur more frequently in adult forms. Abnormalities of eye movements are also common and can be the presenting sign. Eye movement disorders can be classified as central or peripheral. Central forms are frequently observed in lysosomal storage disorders, whereas peripheral forms are a key feature of mitochondrial disease. Furthermore, oculogyric crisis is an important feature in disorders affecting dopamine syntheses or transport. Ocular motor disorders are often not reported by the patient, and abnormalities can be easily overlooked in a general examination. In adults with unexplained psychiatric and neurological symptoms, a special focus on examination of eye movements can serve as a relatively simple clinical tool to detect a metabolic disorder. Eye movements can be easily quantified and analyzed with video‐oculography, making them a valuable biomarker for following the natural course of disease or the response to therapies. Here, we review, for the first time, eye movement disorders that can occur in inborn errors of metabolism, with a focus on late‐onset forms. We provide a step‐by‐step overview that will help clinicians to examine and interpret eye movement disorders. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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Ophthalmic features ofPLA2G6-related paediatric neurodegeneration with brain iron accumulation

Cited by 14 publications

References 10 publications

PLA2G6-Associated Neurodegeneration (PLAN): Review of Clinical Phenotypes and Genotypes

PLA2G6-Associated Neurodegeneration (PLAN): Review of Clinical Phenotypes and Genotypes

Eye Movements in Parkinson’s Disease and Inherited Parkinsonian Syndromes

Eye movement disorders and neurological symptoms in late‐onset inborn errors of metabolism

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