CUX1-related neurodevelopmental disorder: deep insights into phenotype-genotype spectrum and underlying pathology.

Heterozygous, pathogenic CUX1 variants are associated with global developmental delay or intellectual disability. This study delineates the clinical presentation in an extended cohort and investigates the molecular mechanism underlying the disorder in a Cux1 mouse model. Through international collaboration, we assembled the phenotypic and molecular information for 34 individuals (23 unpublished individuals).

Erratum: Variants in cause a spectrum of X-linked neurodevelopmental disorders and facial dysmorphology.

[This corrects the article DOI: 10.1016/j.xhgg.

Variants in cause a spectrum of X-linked neurodevelopmental disorders and facial dysmorphology.

Loss-of-function variants in () cause Siderius X-linked intellectual disability (ID) syndrome, hereafter called PHF8-XLID. PHF8 is a histone demethylase that is important for epigenetic regulation of gene expression. PHF8-XLID is an under-characterized disorder with only five previous reports describing different predicted loss-of-function variants in eight individuals.

Variants in ADD1 cause intellectual disability, corpus callosum dysgenesis, and ventriculomegaly in humans.

Purpose: Adducins interconnect spectrin and actin filaments to form polygonal scaffolds beneath the cell membranes and form ring-like structures in neuronal axons. Adducins regulate mouse neural development, but their function in the human brain is unknown.

Methods: We used exome sequencing to uncover ADD1 variants associated with intellectual disability (ID) and brain malformations.

Rare deleterious mutations of HNRNP genes result in shared neurodevelopmental disorders.

Background: With the increasing number of genomic sequencing studies, hundreds of genes have been implicated in neurodevelopmental disorders (NDDs). The rate of gene discovery far outpaces our understanding of genotype-phenotype correlations, with clinical characterization remaining a bottleneck for understanding NDDs. Most disease-associated Mendelian genes are members of gene families, and we hypothesize that those with related molecular function share clinical presentations.

Tissue variations of mosaic genome-wide paternal uniparental disomy and phenotype of multi-syndromal congenital hyperinsulinism.

Mosaic genome-wide paternal uniparental disomy (GW-pUPD) is a rarely recognised disorder. The phenotypic manifestations of multilocus imprinting defects (MLIDs) remain unclear. We report of an apparently non-syndromic infant with severe congenital hyperinsulinism (CHI) and diffuse pancreatic labelling by 18F*-DOPA-PET/CT leading to near-total pancreatectomy.

Neurologic phenotypes associated with / mutations: Expanding the spectrum of disease.

Objective: To characterize the neurologic phenotypes associated with mutations and to seek genotype-phenotype correlation.

Methods: We analyzed clinical, EEG, and neuroimaging data of 44 new and 55 previously reported patients with mutations.

Results: Childhood-onset focal seizures, frequently complicated by status epilepticus and resistance to antiepileptic drugs, was the most common phenotype.

De Novo Variants in GRIA4 Lead to Intellectual Disability with or without Seizures and Gait Abnormalities.

Using trio whole-exome sequencing, we have identified de novo heterozygous pathogenic variants in GRIA4 in five unrelated individuals with intellectual disability and other symptoms. GRIA4 encodes an AMPA receptor subunit known as GluR4, which is found on excitatory glutamatergic synapses and is important for learning and memory. Four of the variants are located in the highly conserved SYTANLAAF motif in the transmembrane protein M3, and the fifth is in an extra-cellular domain.

Both Low Blood Glucose and Insufficient Treatment Confer Risk of Neurodevelopmental Impairment in Congenital Hyperinsulinism: A Multinational Cohort Study.

Background/aims: Congenital hyperinsulinism (CHI) is a heterogeneous disease most frequently caused by KATP-channel (ABCC8 and KCNJ11) mutations, with neonatal or later onset, variable severity, and with focal or diffuse pancreatic involvement as the two major histological types. CHI confers a high risk of neurological impairment; however, sparsely studied in larger patient series. We assessed the neurodevelopmental outcome in children with CHI at follow-up in a mixed international cohort.

The use of instrumented gait analysis for individually tailored interdisciplinary interventions in children with cerebral palsy: a randomised controlled trial protocol.

Background: Children with cerebral palsy (CP) often have an altered gait. Orthopaedic surgery, spasticity management, physical therapy and orthotics are used to improve the gait. Interventions are individually tailored and are planned on the basis of clinical examinations and standardised measurements to assess walking ('care as usual').

[Neurodegeneration with brain iron accumulation].

Neurodegeneration with brain iron accumulation (NBIA) is a heterogeneous group of syndromes. Whereas NBIA1 (panto-thenate kinase-associated neurodegeneration) has been known since 1922, some of the other diseases in the NBIA group have just been known for a few years. We present the case of a 16-year-old man who recently was diagnosed with NBIA4.

Positive experience with intrathecal baclofen treatment in children with severe cerebral palsy.

Introduction: Treatment of severe spasticity and dystonia with intrathecal baclofen (ITB) in children has been shown to be effective and has therefore been employed in the Region of Southern Denmark. The aim of this retrospective study was to analyse the efficacy and adverse events since ITB was introduced in 2003.

Methods: A total of 46 children who had a baclofen pump from April 2003 to January 2013 were included.

[Early-onset epileptic encephalopathy caused by CDKL5 mutation].

Two girls suffering from early-onset epileptic encephalopathy are described. Both girls had changes involving the gene CDKL5. They both had seizures in the first weeks of life and normal EEG interictally.

[Febrile infection-related status epilepticus in a child after a common infection].

A 13-year-old boy developed seizures and intractable status epilepticus a week after having had a sore throat. Ketogenic diet possibly had some effect. Antibodies to calmodulin dependent protein kinase II were found and could possibly suggest an immunologic aetiology.

[Facial angiofibromas associated to tuberous sclerosis treated with topical sirolimus].

We present a five-year-old boy with facial angiofibromas associated to tuberous sclerosis successfully treated with topical sirolimus 0.4% applied three times a week for six months. After six months we observed a nearly complete resolution of facial angiofibromas.

[Genetic causes of infantile spasms--a systematic review].

Infantile spasms are a symptom of a severe epileptic encephalopathy. It is important to determine the aetiology for a child's disease. When a standard programme for evaluating the aetiology of the infantile spasms is unsuccessful genetic causes should be considered.

[Selenoprotein-related muscular dystrophy].

A nine year-old girl with selenoprotein-related muscular dystrophy was diagnosed. The primary symptom was weak neck muscles. During childhood she developed a rigid spine and over a period of a few years a severe scoliosis.

Effect of a clown's presence at botulinum toxin injections in children: a randomized, prospective study.

Background: The effect of the presence of a hospital clown during pediatric procedures has rarely been evaluated. In a pediatric ward, botulinum toxin injection is a painful procedure and a stressful experience for the child. We undertook a study of the effect of the presence of a hospital clown on children treated with botulinum toxin in an outpatient setting.

[Metformin treatment causes persisting lactic acidosis after cardiac arrest].

Metformin associated lactic acidosis (MALA) is a rare condition with a prevalence of 3 per 100,000 patient-years. The reported mortality is about 50%. We describe a case of MALA in a 61-year-old obese, type II diabetic male who suffered a sudden cardiac arrest.

[Epilepsy treatment by vagus nerve stimulation].

Epilepsy is a common neurological disorder, and between one fourth and one third of the patients do not obtain seizure freedom after treatment with antiepileptic drugs. If the epileptic seizures in such patients have severe consequences, the patients should be assessed for epilepsy surgery. In case epilepsy surgery is not feasible, vagus nerve stimulation (VNS) should be offered.

Does a solitary lobar collapse give pressure-lung volume relationship similar to that found in acute respiratory distress syndrome? A porcine experimental study.

Background: The underlying pathophysiology causing different shapes of static pressure-lung volume (PV) curves is not fully elucidated. In this study the aim was to examine the influence of a solitary lobar collapse on inflation-deflation PV curves. The hypothesis was that a lobar collapse would induce the same changes in the PV-curve as those found in experimental acute lung injury (ALI) and in acute respiratory distress syndrome (ARDS).

Are selective lung recruitment maneuvers hemodynamically safe in severe hypovolemia? An experimental study in hypovolemic pigs with lobar collapse.

Background: We have previously shown, in normovolemic pigs, that a selective lung recruitment maneuver (S-LRM), i.e., insufflation of air-oxygen via a balloon catheter with its tip located in the bronchus of a collapsed lung lobe, effectively improves oxygenation and lung volume without affecting hemodynamics negatively.

Pallister-Killian syndrome: Multiband FISH of tetrasomy 12p.

Two patients with mosaicism for tetrasomy 12p are described. One was diagnosed at the age of 14 years with severe mental retardation and other dysmorphologic findings and abnormal skin pigmentation. Chromosome analysis of a blood sample showed a normal female karyotype.