Kling Chong

• Lecturer at University College London

Volumes of hippocampal subregions in a patient with Developmental Amnesia and a healthy control. Voxel-based morphometry analysis comparing patients with developmental amnesia to healthy controls.

Despite bilateral hippocampal damage dating to the perinatal or early childhood period and severely impaired episodic memory, patients with developmental amnesia continue to exhibit well‐developed semantic memory across the developmental trajectory. Detailed information on the extent and focality of brain damage in these patients is needed to hypot...

Hypoxia‐ischaemia (HI) can result in structural brain abnormalities, which in turn can lead to behavioural deficits in various cognitive and motor domains, in both adult and paediatric populations. Cardiorespiratory arrest (CA) is a major cause of hypoxia‐ischaemia in adults, but it is relatively rare in infants and children. While the effects of a...

Despite bilateral hippocampal damage dating to perinatal or early-childhood period, and severely-impaired episodic memory that unfolds in later childhood, patients with developmental amnesia continue to exhibit well-developed semantic memory across the developmental trajectory. Detailed information on the extent and focality of brain damage in thes...

Objective To describe 10-year follow-up of children <16 years with acquired demyelinating syndromes (ADS) from a UK-wide prospective surveillance study. Methods Diagnoses were retrieved from the patients’ records via the patients’ paediatric or adult neurolo- gist using a questionnaire. Demyelinating phenotypes, at follow-up, were classified by ex...

Background Although therapeutic hypothermia reduces death or disability after neonatal encephalopathy in high-income countries, its safety and efficacy in low-income and middle-income countries is unclear. We aimed to examine whether therapeutic hypothermia alongside optimal supportive intensive care reduces death or moderate or severe disability a...

Bilateral basal ganglia abnormalities on MRI are observed in a wide variety of childhood disorders. MRI pattern recognition can enable rationalisation of investigations and also complement clinical and molecular findings, particularly confirming genomic findings and also enabling new gene discovery. A pattern recognition approach in children with b...

Acute sentinel hypoxia-ischaemia in neonates can target the hippocampus, mammillary bodies, thalamus, and the basal ganglia. Our previous work with paediatric patients with a history of hypoxia-ischaemia has revealed hippocampal and diencephalic damage that impacts cognitive memory. However, the structural and functional status of other brain regio...

Bilateral basal ganglia abnormalities on MRI are observed in a wide variety of childhood disorders. MRI pattern recognition can enable rationalization of investigations and also complement clinical and molecular findings, particularly confirming genomic findings and also enabling new gene discovery. A pattern recognition approach in children with b...

Significance Thyroid hormone deficiencies are the most common preventable causes of intellectual disability. We report that mutations in the thyroid hormone receptor α1 gene ( THRA ) that result in intellectual disability also reduce brain size. Using human THRA mutation stem cell models, we studied the impact of THRA mutations on human brain devel...

Objective To compare the performance of the 2017 McDonald criteria with that of the 2010 criteria for the diagnosis of multiple sclerosis (MS) in children in the clinical setting. Methods In this retrospective, multi-centre study, we identified children who presented with symptoms suggestive of a clinically isolated syndrome (CIS) and were followe...

Background: Nasopharygeal airways are used in urgent situations to alleviate airway obstruction. Guidelines for measuring the length of the NPA differ between national and international guidelines, and the evidence base for these measurements is lacking. The purpose of this study was to measure the nares-epiglottis and nares-vocal cord distances i...

Mutations in the thyroid hormone receptor α 1 gene (THRA) have recently been identified as a cause of intellectual deficit in humans. Patients present with structural abnormalities including microcephaly, reduced cerebellar volume and decreased axonal density. Here, we show that directed differentiation of THRA mutant patient-derived iPSCs to foreb...

Myelin oligodendrocyte glycoprotein antibodies (MOG-Abs) are a well-recognized cause of acquired demyelinating syndromes in both adult and children. Despite basal ganglia involvement on imaging, movement disorder is not a cardinal feature. We describe a 2-year-9-month-old girl who presented with severe encephalopathy with aphasia, seizures and a co...

Purpose Since the online publication of the article, the authors have noted errors with Table 2; this has now been corrected in both the HTML and the PDF.

This case series describes three children with chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS), an inflammatory condition characterized by a relapsing–remitting disease course responsive to steroids. The patients (two males, age 3y and 13y; one female, age 14y) presented with ataxia, dysarthr...

Malformations of cortical development (MCD) are a heterogenous group of disorders with diverse genotypic and phenotypic variations. Lissencephaly is a subtype of MCD caused by defect in neuronal migration, which occurs between 12 and 24 weeks of gestation. The continuous advancement in the field of molecular genetics in the last decade has led to i...

Background and purpose: It has been hypothesized that skull marrow signal alteration may represent an early disease manifestation of Sturge-Weber syndrome before development of its intracranial manifestations. We alternatively hypothesized that intraosseous changes are associated with the overlying port-wine stain rather than the intracranial stig...

Background: Apert syndrome is one of the most common craniosynostosis syndrome caused by mutation in genes encoding fibroblast growth factor receptor 2 (FGFR2). Craniosynostosis, midfacial hypoplasia, and syndactyly/symphalangism are features of this syndrome. Sturge-Weber syndrome (SWS) on the other hand is a congenital neurocutaneous disorder ch...

Intracranial hemorrhage (ICH) in neonates often results in devastating neurodevelopmental outcomes as the neonatal period is a critical window for brain development. The neurodevelopmental outcomes in neonates with ICH are determined by the maturity of the brain, the location and extent of the hemorrhage, the specific underlying etiology and the pr...

Subacute neuroregression in association with raised neopterin and overexpression of interferon stimulated genes (ISGs) could indicate a type 1 interferonopathy. Here we describe a novel immunotherapy-responsive, clinico-immunological and imaging phenotype with evidence of innate immune activation. Three children (patient 1: 22-month-old boy; patien...

Objective: Impairment of speech repetition following injury to the dorsal language stream is feature of conduction aphasia ‐ a well‐described ‘disconnection syndrome' in adults. The impact of similar lesions sustained in infancy has not been established. Methods: We compared language outcomes in term‐born individuals with confirmed neonatal stroke...

Aim: To review the demographics and clinical and paraclinical parameters of children with myelin oligodendrocyte glycoprotein (MOG) antibody-associated relapsing disease. Method: In this UK-based, multicentre study, 31 children with MOG antibody-associated relapsing disease were studied retrospectively. Results: Of the 31 children studied, 14...

Background The prognosis of convulsive status epilepticus (CSE), a common childhood medical neurological emergency, is not well characterised. We aimed to investigate the long-term outcomes in a cohort of participants who previously had CSE. Methods In this prospective study, we followed up a population-based childhood CSE cohort from north London...

Objective: To characterize the phenotypic spectrum, molecular genetic findings, and functional consequences of pathogenic variants in early-onset KCNT1 epilepsy. Methods: We identified a cohort of 31 patients with epilepsy of infancy with migrating focal seizures (EIMFS) and screened for variants in KCNT1 using direct Sanger sequencing, a multip...

Objective: To establish whether children with relapsing acquired demyelinating syndromes (RDS) and myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) show distinctive clinical and radiologic features and to generate a diagnostic algorithm for the main RDS for clinical use. Methods: A panel reviewed the clinical characteristics, MOG-Ab and a...

Few studies have addressed the long-term outcomes of early brain injury, especially after hemorrhagic stroke. This is the first study to report a case of acquired auditory processing disorder in a 10-year-old child who had a severe left hemorrhagic cerebral infarction at 13 months of age, compromising nearly all of the left temporal lobe. This case...

Few studies have addressed the long-term outcomes of early brain injury, especially after hemorrhagic stroke. This is the first study to report a case of acquired auditory processing disorder in a 10-year-old child who had a severe left hemorrhagic cerebral infarction at 13 months of age, compromising nearly all of the left temporal lobe. This case...

PurposeMutations in POLG, the most common single-gene cause of inherited mitochondrial disease, are diagnostically challenging owing to clinical heterogeneity and overlap between syndromes. We aimed to improve the clinical recognition of POLG-related disorders in the pediatric population.Methods We performed a multinational, phenotype: genotype stu...

Appendix S1. Clinical phenotyping statistics for this prospectively recruited cohort of 448 patients with congenital melanocytic naevi.

Background Advances in molecular genetic technologies have improved our understanding of genetic causes of rare neurological disorders with features of myoclonus. Case Report A family with two affected siblings, presenting with multifocal polymyoclonus and neurodevelopmental delay, was recruited for whole-exome sequencing following unyielding diag...

Background: Advances in molecular genetic technologies have improved our understanding of genetic causes of rare neurological disorders with features of myoclonus. Case Report: A family with two affected siblings, presenting with multifocal polymyoclonus and neurodevelopmental delay, was recruited for whole-exome sequencing following unyielding dia...

Mutations in SLC25A22 are known to cause neonatal epileptic encephalopathy and migrating partial seizures in infancy. Using whole exome sequencing we identified four novel SLC25A22 mutations in six children from three families. Five patients presented clinical features similar to those in the literature including hypotonia, refractory neonatal-onse...

Objectives This UK-wide study defines the natural history of argininosuccinic aciduria and compares long-term neurological outcomes in patients presenting clinically or treated prospectively from birth with ammonia-lowering drugs. Methods Retrospective analysis of medical records prior to March 2013, then prospective analysis until December 2015. B...

Background Paediatric relapsing demyelinating syndromes of the CNS define a group of diseases that have different phenotypes. Although for some of them, such as multiple sclerosis and neuromyelitis optica spectrum disorder (NMOSD), diagnostic criteria have been developed, diagnostic uncertainties are not uncommon. We aimed to identify the key featu...

What's already known about this topic? Multiple congenital melanocytic naevi (CMN) are the greatest risk factor for paediatric melanoma. Different clinical phenotypes have different risks of malignancy; however, the overall absolute risk for all types of CMN taken together is low. CMN can develop proliferative nodules that can cause diagnostic unce...

Routine childhood vaccination against measles, mumps and rubella has virtually abolished virus-related morbidity and mortality. Notwithstanding this, we describe here devastating neurological complications associated with the detection of live-attenuated mumps virus Jeryl Lynn (MuVJL5) in the brain of a child who had undergone successful allogeneic...

Histone lysine methylation, mediated by mixed-lineage leukemia (MLL) proteins, is now known to be critical in the regulation of gene expression, genomic stability, cell cycle and nuclear architecture. Despite MLL proteins being postulated as essential for normal development, little is known about the specific functions of the different MLL lysine m...

Pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, functions as a cofactor in humans for more than 140 enzymes, many of which are involved in neurotransmitter synthesis and degradation. A deficiency of PLP can present, therefore, as seizures and other symptoms that are treatable with PLP and/or pyridoxine. Deficiency of PLP in the brain c...

Neonatal hypoxia can lead to hippocampal atrophy, which can lead, in turn, to memory impairment. To test the generalisability of this causal sequence, we examined a cohort of 41 children aged 8-16, who, having received the arterial switch operation to correct for transposition of the great arteries, had sustained significant neonatal cyanosis but w...

Introduction Infectious and immune-mediated encephalitides are important but under-recognised causes of morbidity and mortality in childhood, with a 7% death rate and up to 50% morbidity after prolonged follow-up. There is a theoretical basis for ameliorating the immune response with intravenous immunoglobulin (IVIG), which is supported by empirica...

This article refers to the article that can be found at doi: 10.1007/s00467-016-3465-7.

Developmental amnesia is a selective episodic memory disorder associated with hypoxia-induced bilateral hippocampal atrophy of early onset. Despite the systemic impact of hypoxia-ischaemia, the resulting brain damage was previously reported to be largely limited to the hippocampus. However, the thalamus and the mammillary bodies are parts of the hi...

Background: TRNT1 (CCA-adding transfer RNA nucleotidyl transferase) enzyme deficiency is a new metabolic disease caused by defective post-transcriptional modification of mitochondrial and cytosolic transfer RNAs (tRNAs). Results: We investigated four patients from two families with infantile-onset cyclical, aseptic febrile episodes with vomiting...

This study aimed to evaluate cerebral magnetic resonance imaging (MRI) scans of children with prenatal drug exposure in a clinical context. A hospital-based cohort of 10- to 14-year-old children, prenatally exposed to alcohol, opioids, and polysubstances, and a group of sex- and age-matched controls were examined with cerebral MRI. Scans obtained f...

Although manganese is an essential trace metal, little is known about its transport and homeostatic regulation. Here we have identified a cohort of patients with a novel autosomal recessive manganese transporter defect caused by mutations in SLC39A14. Excessive accumulation of manganese in these patients results in rapidly progressive childhood-ons...

Compared to the illnesses encountered in the ageing populations of the developed world, illness in children is relatively uncommon. Basic societal hygiene and healthcare provision is supportive of paediatric populations which are mostly healthy. When illness occurs, some of the diseases may be unusual or only rarely encountered. This has led to the...

Epilepsy most often begins in childhood and is therefore an important paediatric disorder. Seizures, which are abnormal movements or behaviour which result from abnormal electrical activity in the brain, are a symptom of epilepsy. Not all patients who appear to have seizures have epilepsy. Epilepsy is the group of disorders which are characterised...

A five-year-old girl was referred to our department for evaluation of a pigmented birthmark on her right cheek, present unchanged since birth. There was no other past medical history of note and no family history of relevant problems. Cutaneous examination revealed a pigmented keratinocytic epidermal naevus following fine Blaschko's lines on the ri...

We report the case of a young girl who presented with hemiparesis, seizures, and subtle features consistent with a linear form of facial morphea (en coup de sabre). She was treated with pulsed parenteral steroids and oral steroids and started on methotrexate. Magnetic resonance imaging results and neurologic problems improved after 6 months. Switch...

Common birthmarks can be an indicator of underlying genetic disease, but are often overlooked. Mongolian Blue Spots (dermal melanocytosis) are usually localized and transient, but can be extensive, permanent and associated with extra-cutaneous abnormalities. Co-occurrence with vascular birthmarks defines a subtype of Phakomatosis Pigmentovascularis...

Introduction Les taches mongoliques, correspondant à une mélanocytose dermique, sont fréquentes à la naissance mais généralement transitoires. Elles peuvent parfois persister isolément ou en association à des angiomes plans dans les phacomatoses pigmento-vasculaires (types cesioflammea et cesiomarmorata), affections où nous avons identifié des muta...

Objectives: To compare the diagnostic yield of whole-body post-mortem computed tomography (PMCT) imaging to post-mortem magnetic resonance (PMMR) imaging in a prospective study of fetuses and children. Methods: We compared PMCT and PMMR to conventional autopsy as the gold standard for the detection of (a) major pathological abnormalities related...

Background: Paediatric Listeria meningitis is rare, especially in immuno-competent children, but associated with significant mortality and morbidity and frequent complications. Methods: We report an unusual case of Listeria meningitis in a previously healthy 35 month-old girl with selective spinal grey matter involvement and demyelination in neu...

Appendix S1. Regression analysis.

Neurodegeneration with brain iron accumulation (NBIA) is an umbrella term used to clinically describe a group of neurologic conditions associated with high brain iron. To date, there are 10 genetic subtypes described, which share several common clinical features. Novel technologies such as improved magnetic resonance imaging techniques and whole ex...

Deliberate inflicted trauma to children has irrefutably occurred for centuries but the notion of non-accidental injury (NAI) as a distinct clinical entity has only relatively recently been described. Awareness and understanding of this syndrome of abuse has increased greatly in recent decades, although many alternative names have been given to the...

To compare the diagnostic accuracy of non-invasive cerebral post-mortem magnetic resonance imaging (PMMRI) specifically for cerebral and neurological abnormalities in a series of fetuses and children, compared to conventional autopsy. Institutional ethics approval and parental consent was obtained. Pre-autopsy cerebral PMMRI was performed in a sequ...

Background: The spectrum of central nervous system (CNS) abnormalities described in association with congenital melanocytic naevi (CMN) includes congenital, acquired, melanotic and nonmelanotic pathology. Historically, symptomatic CNS abnormalities were considered to carry a poor prognosis, although studies from large centres have suggested a much...

Objective: To explore the structure-function relation of the temporal lobe in newly diagnosed West syndrome of unknown cause (uWS). / Methods: Quantitative magnetic resonance imaging (3D structural MRI and diffusion tensor imaging, DTI) was analysed by voxel-based morphometry (VBM) and tractbased spatial statistics (TBSS) in 22 patients and healthy...

Synaptotagmin-1 (SYT1) is a calcium-binding synaptic vesicle protein that is required for both exocytosis and endocytosis. Here, we describe a human condition associated with a rare variant in SYT1. The individual harboring this variant presented with an early onset dyskinetic movement disorder, severe motor delay, and profound cognitive impairment...

To expand the clinical phenotype of autosomal dominant congenital spinal muscular atrophy with lower extremity predominance (SMA-LED) due to mutations in the dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene. Patients with a phenotype suggestive of a motor, non-length-dependent neuronopathy predominantly affecting the lower limbs were identified...

Paediatric cerebrovascular CT angiography (CTA) can be challenging to perform due to variable cardiovascular physiology between different age groups and the risk of movement artefact. This analysis aimed to determine what proportion of CTA at our institution was of diagnostic quality and identify technical factors which could be improved. a retrosp...

IntroductionIntensive postsurgical therapies have improved survival in children with primitive neuroectodermal tumour, but there is concern that the combination of chemotherapy and radiotherapy may result in a compound injury to normal brain. The purposes of this analysis were to characterise what types of imaging abnormalities occur, identify risk...

Phospholipase A2 associated neurodegeneration (PLAN) is a major phenotype of autosomal recessive Neurodegeneration with Brain Iron Accumulation (NBIA). We describe the clinical phenotypes, neuroimaging features and PLA2G6 mutations in 5 children, of whom 4 presented with infantile neuroaxonal dystrophy (INAD). One other patient was diagnosed with t...

PNPO mutations that had reduced enzyme activity were identified: (i) patients with neonatal onset seizures responding to pyridoxal 5’-phosphate (n = 6); (ii) a patient with infantile spasms (onset 5 months) responsive to pyridoxal 5’-phosphate (n = 1); and (iii) patients with seizures starting under 3 months of age responding to pyridoxine (n = 8)....

Background: The severe neurodevelopmental phenotype of untreated congenital hypothyroidism exemplifies the critical role of thyroid hormones (TH) in CNS development, acting via thyroid hormone receptor α1 (TRα1) on cortical neurogenesis, cerebellar development and oligodendrocyte differentiation. We have identified the first humans with defective T...

Neonates treated for acute respiratory failure experience episodes of hypoxia. The hippocampus, a structure essential for memory, is particularly vulnerable to such insults. Hence, some neonates undergoing treatment for acute respiratory failure might sustain bilateral hippocampal pathology early in life and memory problems later in childhood. We i...

Wernicke's encephalopathy is a triad of ophthalmoplegia, ataxia and confusion seen in alcoholics with dietary vitamin B1 (thiamine) deficiency. A rare genetic defect of thiamine transporter-2 may lead to similar clinical features, biotin-thiamine responsive basal ganglia disease (BTBGD). A 15-year-old girl developed rapid onset ptosis and ophthalmo...

We describe a previously unreported syndrome characterized by secondary (post-natal) microcephaly with fronto-temporal lobe hypoplasia, multiple pituitary hormone deficiency, seizures, severe visual impairment and abnormalities of the kidneys and urinary tract in a highly consanguineous family with six affected children. Homozygosity mapping and ex...

Recently, we reported a previously unrecognized symptom constellation comprising epilepsy, ataxia, sensorineural deafness, and tubulopathy (EAST syndrome) associated with recessive mutations in the KCNJ10 gene. Here, we provide a detailed characterization of the clinical features of the syndrome to aid patient management with respect to diagnosis,...

Premature birth may be associated with white matter injury later developing with widening of the ventricles. However, population-based data on normal ventricular size by age are sparse, making the evaluation of possible ventricular dilatation difficult. To present the linear measurements of the ventricular system, to compare these to subjectively a...