Genetic Heterogeneity Underlying Phenotypes with Early-Onset Cerebellar Atrophy.

Cerebellar atrophy (CA) is a frequent neuroimaging finding in paediatric neurology, usually associated with cerebellar ataxia. The list of genes involved in hereditary forms of CA is continuously growing and reveals its genetic complexity. We investigated ten cases with early-onset cerebellar involvement with and without ataxia by exome sequencing or by a targeted panel with 363 genes involved in ataxia or spastic paraplegia.

ClinPrior: an algorithm for diagnosis and novel gene discovery by network-based prioritization.

Background: Whole-exome sequencing (WES) and whole-genome sequencing (WGS) have become indispensable tools to solve rare Mendelian genetic conditions. Nevertheless, there is still an urgent need for sensitive, fast algorithms to maximise WES/WGS diagnostic yield in rare disease patients. Most tools devoted to this aim take advantage of patient phenotype information for prioritization of genomic data, although are often limited by incomplete gene-phenotype knowledge stored in biomedical databases and a lack of proper benchmarking on real-world patient cohorts.

A novel TRMT5 mutation causes a complex inherited neuropathy syndrome: The role of nerve pathology in defining a demyelinating neuropathy.

Aims: We aim to present data obtained from three patients belonging to three unrelated families with an infantile onset demyelinating neuropathy associated to somatic and neurodevelopmental delay and to describe the underlying genetic changes.

Methods: We performed whole-exome sequencing on genomic DNA from the patients and their parents and reviewed the clinical, muscle and nerve data, the serial neurophysiological studies, brain and muscle MRIs, as well as the respiratory chain complex activity in the muscle of the three index patients. Computer modelling was used to characterise the new missense variant detected.

Extending the Phenotype Related to Gene: Arthrogryposis, Movement Disorders, and Malformations of Cortical Development.

Background: Expand the knowledge about the clinical phenotypes associated with pathogenic or likely pathogenic variants in the gene.

Methods: The study was carried out in 15 patients with variants. The complete phenotype of the patients was evaluated.

Case Report: Novel Homozygous Likely Pathogenic Variant With Autosomal Recessive Inheritance and Review of the Literature.

Dominant pathogenic variations in the gene are associated with several neuro developmental disorders with or without epilepsy, including Dravet syndrome (DS). Conversely, there are few published cases with homozygous or compound heterozygous variations in the gene. Here, we describe two siblings from a consanguineous pedigree with epilepsy phenotype compatible with genetic epilepsy with febrile seizures plus (GEFS+) associated with the homozygous likely pathogenic variant (NM_001165963.

Mitochondrial developmental encephalopathy with bilateral optic neuropathy related to homozygous variants in IMMT gene.

IMMT gene codes for mitofilin, a mitochondrial inner membrane protein that regulates the morphology of mitochondrial cristae. The phenotype associated with mutations in this gene has not been yet established, but functional studies carried out show that its loss causes a mitochondrial alteration, both in the morphology of the mitochondrial crests and in their function. We present two cousins from an extended highly consanguineous family with developmental encephalopathy, hypotonia, nystagmus due to optic neuropathy.

[Moyamoya disease: revision and description of a number of pedriatic cases].

Introduction: Moyamoya disease is caused because of progressive occlusion of the arterial circle of Willis, leading to a compensatory net-like abnormal vessels development. The objective is to describe the number of cases in our center (tertiary hospital).

Patients And Methods: Retrospective study.

Extending the clinical phenotype of SPTAN1: From DEE5 to migraine, epilepsy, and subependymal heterotopias without intellectual disability.

Mutations in SPTAN1 gene, encoding the nonerythrocyte αII-spectrin, are responsible for a severe developmental and epileptic encephalopathy (DEE5) and a wide spectrum of neurodevelopmental disorders, as epilepsy with or without intellectual disability (ID) or ID with cerebellar syndrome. A certain genotype-phenotype correlation has been proposed according to the type and location of the mutation. Herein, we report three novel cases with de novo SPTAN1 mutations, one of them associated to a mild phenotype not previously described.

Venous sinus thrombosis in pediatrics. Case series of a tertiary hospital.

Introduction: Venous sinus thrombosis (VST) is a rare entity in pediatrics, probably under-diagnosed and poten tially serious, described as a cause of stroke in childhood.

Objective: To describe the clinical presenta tion, risk factors, treatment, and evolution of pediatric patients with VST.

Patients And Method: Re trospective study of patients admitted to a referral hospital, diagnosed with VST, aged between one month and seventeen years, from January 2011 to December 2019.

Pediatric inherited peripheral neuropathy: a prospective study at a Spanish referral center.

Background: Single-center clinical series provide important information on genetic distribution that can guide genetic testing. However, there are few such studies on pediatric populations with inherited peripheral neuropathies (IPNs).

Methods: Thorough genetic testing was performed on IPN patients under 20 years of age from a geographically well-defined Mediterranean area (Valencian Community, Spain), annually assessed with the Charcot-Marie-Tooth disease Pediatric Scale (CMTPedS).

Variant in as a Possible Genetic Modifier of Neonatal Epilepsy in an Infant with a De Novo Mutation.

Mutations in genes have been described in patients with epilepsy, finding a large phenotypic variability, from benign familial epilepsy to epileptic encephalopathy. To explain this variability, it was proposed the existence of dominant modifier alleles at one or more loci that contribute to determine the severity of the epilepsy phenotype. One example of modifier factor may be the gene, as proved in animal models.

[Megalencephalic leukoencephalopathy with cysts -the clinical importance in the genetic era].

Introduction: Megalencephalic leukoencephalopathy with cysts is a leukodystrophy of genetic origin that produces an alteration in the water and ion homeostasis in the brain, generating vacuolar forms and chronic oedema in the white matter with progressive neurological deterioration. It should be suspected in infants who present progressive macrocephaly during the first year of life, motor retardation and characteristic findings in magnetic resonance brain scans.

Case Report: We report the case of a girl who was followed up from the age of 9 months due to progressive macrocephaly and delayed psychomotor development and brain MRI findings consistent with megalencephalic leukoencephalopathy with cysts, and the appearance of epilepsy during its development.

[Neurological sequelae in patients with congenital cytomegalovirus].

Introduction: The infection due to cytomegalovirus is the most common congenital infection in developed countries, and on of the main causes of psychomotor impairment and neurosensory hearing loss of infectious origin. The present study has its objectives to describe the clinical-analytical and neuroimaging of patients with secondary neurological sequelae secondary to the congenital cytomegalovirus infection and then compare them with the group of patients with a congenital cytomegalovirus infection that did not have neurological symptoms during their follow-up.

Material And Methods: A retrospective, observational, cohort study was conducted that included all the cases of congenital cytomegalovirus infection from 2003 until 2018 and the short-medium term neurological sequelae were evaluated.

Associations of paediatric demyelinating and encephalitic syndromes with myelin oligodendrocyte glycoprotein antibodies: a multicentre observational study.

Background: Investigations of myelin oligodendrocyte glycoprotein (MOG) antibodies are usually focused on demyelinating syndromes, but the entire spectrum of MOG antibody-associated syndromes in children is unknown. In this study, we aimed to determine the frequency and distribution of paediatric demyelinating and encephalitic syndromes with MOG antibodies, their response to treatment, and the phenotypes associated with poor prognosis.

Methods: In this prospective observational study, children with demyelinating syndromes and with encephalitis other than acute disseminated encephalomyelitis (ADEM) recruited from 40 secondary and tertiary centres in Spain were investigated for MOG antibodies.

[HaNDL syndrome in a 12-year-old girl].

Introduction: HaNDL (headache and neurological deficits with cerebrospinal fluid lymphocytosis) syndrome is a self-limiting benign condition which, as its name suggests, causes episodes of transient neurological deficits of a motor, sensory, aphasic and, less frequently, visual nature lasting several hours, accompanied or followed by moderate-to-severe headache and lymphocytosis of the cerebrospinal fluid. Its incidence is low in adulthood, and it is extremely uncommon in the paediatric age. Recurrence of episodes usually occurs in the first three months.

A Novel Mutation of in a Patient with Schaaf-Yang Syndrome and Hypopituitarism.

Introduction: Schaaf-Yang syndrome (SYS) is caused by truncating point mutations of the paternal allele of , an imprinted gene located in the critical region of Prader-Willi syndrome (PWS). These patients present a phenotype with neurodevelopmental delay, hypotonia, joint contractures, and a particularly high prevalence of autism (up to 75% in affected individuals). The loss of function of is suggested to contribute to endocrine hypothalamic dysfunction in individuals with PWS.

Clinical rating scale for pantothenate kinase-associated neurodegeneration: A pilot study.

Background: Pantothenate kinase-associated neurodegeneration is a progressive neurological disorder occurring in both childhood and adulthood. The objective of this study was to design and pilot-test a disease-specific clinical rating scale for the assessment of patients with pantothenate kinase-associated neurodegeneration.

Methods: In this international cross-sectional study, patients were examined at the referral centers following a standardized protocol.

The importance of biochemical and genetic findings in the diagnosis of atypical Norrie disease.

Background: Norrie disease (ND) is a rare X-linked disorder characterized by bilateral congenital blindness. ND is caused by a mutation in the Norrie disease pseudoglioma (NDP) gene, which encodes a 133-amino acid protein called norrin. Intragenic deletions including NDP and adjacent genes have been identified in ND patients with a more severe neurologic phenotype.

[Neurological appraisal of children and adolescents with psychotic symptoms].

Introduction: Psychotic manifestations in childhood are not infrequent, yet the existing literature dealing with the neurological appraisal of children and adolescents with a clinical picture of psychosis is very scant.

Aim: To conduct a non-systematic review of the literature that provides an answer to these three questions: When must a neurological appraisal be performed in a child with psychotic traits? What medical conditions can include signs and symptoms of psychosis in their development? And, what diagnostic procedure should be followed?

Development: The diseases that can present psychotic symptoms at onset or during their course are reviewed and grouped by pathologies: inborn errors of metabolism, genetic diseases, autoimmune and infectious diseases, malformations of the central nervous system, epilepsy, vascular pathology, rheumatologic processes, brain tumours, and psychoactive substances and drugs. A diagnostic regimen is proposed in which both the information obtained from the anamnesis and examination and the findings from each of the diagnostic tests are evaluated.

[Hypomyelination with atrophy of the basal ganglia and cerebellum. Contribution of two new cases to a recently reported entity].

Introduction: Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a rare condition that has only recently been reported. Here we present two new cases belonging to the same family.

Case Reports: Case 1: 17-month-old boy with severe underdevelopment in all areas, absence of language and eye contact.

[Clinico-radiological profile of acute disseminated encephalomyelitis in the childhood population. A retrospective analysis of a series of 20 patients in a tertiary hospital].

Introduction: Acute disseminated encephalomyelitis (ADE) is an inflammatory disorder of the central nervous system that is mediated immunologically and of unknown pathogenesis. It can present at any age, but is much more frequent in children. ADE has no specific biological marker and diagnosis is based on findings from clinical and neuroimaging studies.