Clinical and Molecular Spectrum of Autosomal Recessive CA8-Related Cerebellar Ataxia.

Background: Based on a limited number of reported families, biallelic CA8 variants have currently been associated with a recessive neurological disorder named, cerebellar ataxia, mental retardation, and dysequilibrium syndrome 3 (CAMRQ-3).

Objectives: We aim to comprehensively investigate CA8-related disorders (CA8-RD) by reviewing existing literature and exploring neurological, neuroradiological, and molecular observations in a cohort of newly identified patients.

Methods: We analyzed the phenotype of 27 affected individuals from 14 families with biallelic CA8 variants (including data from 15 newly identified patients from eight families), ages 4 to 35 years.

The gain of function SCN1A disorder spectrum: novel epilepsy phenotypes and therapeutic implications.

Brain voltage-gated sodium channel NaV1.1 (SCN1A) loss-of-function variants cause the severe epilepsy Dravet syndrome, as well as milder phenotypes associated with genetic epilepsy with febrile seizures plus. Gain of function SCN1A variants are associated with familial hemiplegic migraine type 3.

Neurological manifestations of SARS-CoV-2 infection in hospitalised children and adolescents in the UK: a prospective national cohort study.

Background: The spectrum of neurological and psychiatric complications associated with paediatric SARS-CoV-2 infection is poorly understood. We aimed to analyse the range and prevalence of these complications in hospitalised children and adolescents.

Methods: We did a prospective national cohort study in the UK using an online network of secure rapid-response notification portals established by the CoroNerve study group.

Homozygous intronic variants in TPM2 cause recessively inherited Escobar variant of multiple pterygium syndrome and congenital myopathy.

Pathogenic variants in TPM2 have been associated with a variable clinical spectrum, including congenital myopathies and distal arthrogryposis, all but one with dominant inheritance. We report the second case of recessively inherited TPM2-related Escobar variant of multiple pterygium syndrome and congenital myopathy in a patient from a consanguineous family. Ultra-structural examination of the biopsy revealed few cores/mini-cores and sparse nemaline rods.

Carbamazepine Improves Apneic Episodes in Congenital Central Hypoventilation Syndrome (CCHS) With a Novel Exon 1 Missense Mutation.

Pathogenic variants in Paired-Like Homeobox 2B () gene cause congenital central hypoventilation syndrome (CCHS), a rare disorder of the nervous system characterized by absent or reduced ventilatory response to hypoxia and hypercapnia. The focus of management in CCHS is optimizing ventilation. Thus far, no medication has proved effective in improving ventilation.

RMND1-Related Leukoencephalopathy With Temporal Lobe Cysts and Hearing Loss-Another Mendelian Mimicker of Congenital Cytomegalovirus Infection.

Background: Leukoencephalopathy with temporal lobe cysts may be associated with monogenetic conditions such as Aicardi-Goutières syndrome or RNASET2 mutations and with congenital infections such as cytomegalovirus. In view of the fact that congenital cytomegalovirus is difficult to confirm outside the neonatal period, excluding a Mendelian disorder is extremely relevant, changing family planning and medical management in affected families. We performed diagnostic testing in individuals with leukoencephalopathy with temporal lobe cysts without a definitive diagnosis of congenital cytomegalovirus infection.

The clinical, biochemical and genetic features associated with -related mitochondrial disease.

Background: Mutations in the (Required for Meiotic Nuclear Division protein 1) gene have recently been linked to infantile onset mitochondrial disease characterised by multiple mitochondrial respiratory chain defects.

Methods: We summarised the clinical, biochemical and molecular genetic investigation of an international cohort of affected individuals with mutations. In addition, we reviewed all the previously published cases to determine the genotype-phenotype correlates and performed survival analysis to identify prognostic factors.

Homozygous deletion in MICU1 presenting with fatigue and lethargy in childhood.

Objective: To define the mechanism responsible for fatigue, lethargy, and weakness in 2 cousins who had a normal muscle biopsy.

Methods: Exome sequencing, long-range PCR, and Sanger sequencing to identify the pathogenic mutation. Functional analysis in the patient fibroblasts included oxygen consumption measurements, extracellular acidification studies, Western blotting, and calcium imaging, followed by overexpression of the wild-type protein.

Biallelic Mutations in PDE10A Lead to Loss of Striatal PDE10A and a Hyperkinetic Movement Disorder with Onset in Infancy.

Deficits in the basal ganglia pathways modulating cortical motor activity underlie both Parkinson disease (PD) and Huntington disease (HD). Phosphodiesterase 10A (PDE10A) is enriched in the striatum, and animal data suggest that it is a key regulator of this circuitry. Here, we report on germline PDE10A mutations in eight individuals from two families affected by a hyperkinetic movement disorder due to homozygous mutations c.

The prevalence of neuromuscular disease in the paediatric population in Yorkshire, UK; variation by ethnicity and deprivation status.

Aim: Previous studies suggest a higher prevalence of neurological disease within certain ethnic communities, but have not specifically considered neuromuscular diseases (NMDs). The aim of this study was to calculate the prevalence and relationship of NMDs to ethnicity and deprivation status.

Method: We undertook a retrospective case-note review of those younger than 16 years with a confirmed diagnosis of NMD in a single centre in Yorkshire in 2010.

Experience of mechanical thrombectomy for paediatric arterial ischaemic stroke.

Background: Paediatric arterial ischaemic stroke (AIS) is an important cause of acute neurological symptoms in children, it causes significant morbidity and is one of the top ten causes of childhood deaths. Consensus papers have suggested guidelines for the management of AIS in childhood, although none recommend thrombectomy. Despite this, children within our institution have undergone mechanical thrombectomy for large vessel occlusion.

Spontaneous Dissecting Lenticulostriate Artery Aneurysm in Children: Radiologic Findings and Clinical Management.

Aneurysms involving the lenticulostriate artery (LSA) are rare. The majority of LSA aneurysms reported are idiopathic. We present 2 paediatric cases of dissecting distal LSA aneurysm.

Neurological manifestations of influenza infection in children and adults: results of a National British Surveillance Study.

Background: The emergence of influenza A(H1N1) 2009 was met with increased reports of associated neurological manifestations. We aimed to describe neurological manifestations of influenza in adults and children in the United Kingdom that presented at this time.

Methods: A 2-year surveillance study was undertaken through the British adult and pediatric neurological surveillance units from February 2011.

Loss-of-function mutations in MICU1 cause a brain and muscle disorder linked to primary alterations in mitochondrial calcium signaling.

Mitochondrial Ca(2+) uptake has key roles in cell life and death. Physiological Ca(2+) signaling regulates aerobic metabolism, whereas pathological Ca(2+) overload triggers cell death. Mitochondrial Ca(2+) uptake is mediated by the Ca(2+) uniporter complex in the inner mitochondrial membrane, which comprises MCU, a Ca(2+)-selective ion channel, and its regulator, MICU1.

Intracranial calcification in early infantile Krabbe disease: nothing new under the sun.

We report the cases of three children, one male and two females, with a diagnosis of early infantile Krabbe disease demonstrating intracranial calcification on computed tomography (CT). The pattern of calcification was similar in all individuals and involved the internal capsule and cerebral white matter. The presence of calcification caused some diagnostic confusion in what was otherwise a typical clinical and radiological presentation.

Parental and physician beliefs regarding the provision and content of written sudden unexpected death in epilepsy (SUDEP) information.

Purpose: The 2007 UK National Institute for Health and Clinical Excellence (NICE) guidelines for epilepsy recommend disclosing the risk of sudden unexpected death in epilepsy (SUDEP) to patients. This recommendation is not undertaken routinely, and considerable variation in individual physician practice exists. Literature indicates wariness of causing distress and anxiety, particularly to children/young people and their families through disclosing a nonpreventable risk.

Presumed perinatal stroke in a child with Down syndrome and moyamoya disease.

Moyamoya disease describes a cerebral arteriopathy characterized by stenosis or occlusion of the terminal internal carotid and/or the proximal middle cerebral arteries. We report a female child with trisomy 21 and bilateral moyamoya disease who presented, unusually, with a presumed perinatal cerebral infarct. The clinical, radiological, and angiographic features of moyamoya disease in children with Down syndrome are similar to those with other aetiologies or idiopathic cases.

Cogan's syndrome: a rare cause of meningoencephalitis.

We report a 14-year-old boy who presented with meningoencephalitis. Other features particularly auditory, vestibular, and ocular lead to the diagnosis of Cogan's syndrome. Treatment with prednisolone resulted in a rapid improvement and recovery of his hearing.