Aberrant splicing and transcriptional activity of TPP1 result in CLN2-like disorder.

RNA sequencing (RNAseq) is emerging as a complementary tool to DNA sequencing, providing utility in diagnosis for disorders such as neuronal ceroid lipofuscinosis CLN2 disease. We describe an individual with a presentation suggestive of an attenuated CLN2 phenotype, including a history of regression, recent-onset microcephaly and spasticity from age five years. Exome sequencing revealed two variants inherited in trans in TPP1, NM_000391.

The severe epilepsy syndromes of infancy: A population-based study.

Objective: To study the epilepsy syndromes among the severe epilepsies of infancy and assess their incidence, etiologies, and outcomes.

Methods: A population-based cohort study was undertaken of severe epilepsies with onset before age 18 months in Victoria, Australia. Two epileptologists reviewed clinical features, seizure videos, and electroencephalograms to diagnose International League Against Epilepsy epilepsy syndromes.

Neuronal ceroid lipofuscinosis type 2: an Australian case series.

Aim: Late infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease is a rare neurodegenerative disorder presenting in children aged 2-4 years with seizures and loss of motor and language skills, followed by blindness and death in late childhood. Initial presenting features are similar to a range of common epilepsies. We aim to highlight typical clinical and radiological features that may prompt diagnosis of CLN2 disease in early disease stages.

Cerebral hypomyelination associated with biallelic variants of FIG4.

The lipid phosphatase gene FIG4 is responsible for Yunis-Varón syndrome and Charcot-Marie-Tooth disease Type 4J, a peripheral neuropathy. We now describe four families with FIG4 variants and prominent abnormalities of central nervous system (CNS) white matter (leukoencephalopathy), with onset in early childhood, ranging from severe hypomyelination to mild undermyelination, in addition to peripheral neuropathy. Affected individuals inherited biallelic FIG4 variants from heterozygous parents.

SCN2A encephalopathy: A major cause of epilepsy of infancy with migrating focal seizures.

Objective: De novo SCN2A mutations have recently been associated with severe infantile-onset epilepsies. Herein, we define the phenotypic spectrum of SCN2A encephalopathy.

Methods: Twelve patients with an SCN2A epileptic encephalopathy underwent electroclinical phenotyping.

High resolution chromosomal microarray in undiagnosed neurological disorders.

Aim: Despite advances in medical investigation, many children with neurological conditions remain without a diagnosis, although a genetic aetiology is often suspected. Chromosomal microarray (CMA) screens for copy number variants (CNVs) and long continuous stretches of homozygosity (LCSH) and may further enhance diagnostic yield. Although recent studies have identified pathogenic CNVs in intellectual disability, autism and epilepsy, the utility of CMA testing in a broader cohort of children with neurologic disorders has not been reported.

Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1.

Epileptic encephalopathies are a devastating group of epilepsies with poor prognosis, of which the majority are of unknown etiology. We perform targeted massively parallel resequencing of 19 known and 46 candidate genes for epileptic encephalopathy in 500 affected individuals (cases) to identify new genes involved and to investigate the phenotypic spectrum associated with mutations in known genes. Overall, we identified pathogenic mutations in 10% of our cohort.

Childhood chronic inflammatory demyelinating polyneuropathy: an overview of 10 cases in the modern era.

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.

Guillain-Barré syndrome following pandemic (H1N1) 2009 influenza A immunisation in Victoria: a self-controlled case series.

Objectives: To determine the relative incidence (RI) of Guillain-Barré syndrome (GBS) in a single Australian state following pandemic (H1N1) 2009 influenza A immunisation (monovalent vaccine or seasonal trivalent influenza vaccine [TIV]) in 2009-2010.

Design, Setting And Participants: Active GBS surveillance (cases assessed by two neurologists according to the Brighton criteria) from 30 September 2009 to 30 September 2010, conducted at 10 hospitals in Victoria, Australia.

Main Outcome Measures: The RI of GBS in the risk window of 0-42 days after vaccination.

Atypical childhood chronic inflammatory demyelinating polyneuropathy.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an uncommon cause of progressive weakness in childhood. The diagnosis is easy when the clinical history and findings are supported by unequivocal electrophysiologic and laboratory evidence of demyelination, but it can be challenging if the criteria for demyelination are not met. We report a case of atypical childhood CIDP to highlight the diagnostic difficulties and the importance of recognizing this treatable condition.

Subacute inflammatory demyelinating polyneuropathy in children.

Reported are five children with subacute demyelinating polyneuropathy. All patients had a monophasic disease, progressing over 4 to 8 weeks and characterized by predominantly motor features, areflexia, minimal or no cranial nerve abnormalities, no autonomic or respiratory involvement, elevated CSF protein, electrophysiologic evidence of demyelination, and good response to corticosteroids. A benign course with full recovery was the rule.

Acute tinnitus and hearing loss as the initial symptom of multiple sclerosis in a child.

Acute hearing loss with or without tinnitus has been reported in a number of adult series of multiple sclerosis (MS), but is considered a rare phenomenon. It generally occurs during disease exacerbations, rather than as an isolated finding or presenting feature. We present the case of an 11-year-old girl in whom persistent tinnitus and reversible hearing loss were the sole manifestation of MS at initial presentation.

Childhood chronic inflammatory demyelinating polyneuropathy with central nervous system demyelination resembling multiple sclerosis.

Central nervous system demyelination has been described in adults but not in children with chronic inflammatory demyelinating polyneuropathy. We describe a patient with clinical and electrophysiological features consistent with chronic inflammatory demyelinating polyneuropathy who presented at age 5 with an intramedullary spinal cord tumor-like lesion and at age 8, represented with cerebral and spinal demyelinating lesions. Her clinical course and magnetic resonance imaging features were atypical for multiphasic disseminated encephalomyelitis and indistinguishable from multiple sclerosis.