A neurodevelopmental disorder caused by a dysfunctional allele.

P/Q-type Ca flux into nerve terminals Ca2.1 channels is essential for neurotransmitter release at neuromuscular junctions and nearly all central synapses. Mutations in , the gene encoding Ca2.

Further Characterization of Loss of Function Epilepsy Distinct From Cornelia de Lange Syndrome.

Cornelia de Lange syndrome is a rare developmental malformation syndrome characterized by small stature, limb anomalies, distinctive facial features, developmental delays, and behavioral issues. The diagnosis of Cornelia de Lange syndrome is made clinically or on the basis of an identified variant in one of the genes associated with Cornelia de Lange syndrome. variants are the cause of 5% of the cases of Cornelia de Lange syndrome.

Novel variants in KAT6B spectrum of disorders expand our knowledge of clinical manifestations and molecular mechanisms.

The phenotypic variability associated with pathogenic variants in Lysine Acetyltransferase 6B (KAT6B, a.k.a.

Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway intolerant to genomic variation.

Reversible modification of proteins with linkage-specific ubiquitin chains is critical for intracellular signaling. Information on physiological roles and underlying mechanisms of particular ubiquitin linkages during human development are limited. Here, relying on genomic constraint scores, we identify 10 patients with multiple congenital anomalies caused by hemizygous variants in , encoding a K48/K63 linkage-specific deubiquitylase.

Two siblings with a novel variant of EXOSC3 extended phenotypic spectrum of pontocerebellar hypoplasia 1B to an exceptionally mild form.

Pontocerebellar hypoplasia type 1B (PCH1B) describes an autosomal recessive neurological condition that involves hypoplasia or atrophy of the cerebellum and pons, resulting in neurocognitive impairments. Although there is phenotypic variability, this is often an infantile lethal condition, and most cases have been described to be congenital and neurodegenerative. PCH1B is caused by mutations in the gene EXOSC3, which encodes exosome component 3, a subunit of the human RNA exosome complex.

Posterior Neocortex-Specific Regulation of Neuronal Migration by CEP85L Identifies Maternal Centriole-Dependent Activation of CDK5.

Genes mutated in human neuronal migration disorders encode tubulin proteins and a variety of tubulin-binding and -regulating proteins, but it is very poorly understood how these proteins function together to coordinate migration. Additionally, the way in which regional differences in neocortical migration are controlled is completely unknown. Here we describe a new syndrome with remarkably region-specific effects on neuronal migration in the posterior cortex, reflecting de novo variants in CEP85L.

Relapsing-remitting clinical course expands the phenotype of Aicardi-Goutières syndrome.

Aicardi-Goutières syndrome (AGS) is a rare and likely underdiagnosed genetic leukoencephalopathy, typically presenting in infancy with encephalopathy and characteristic neuroimaging features, with residual static neurological deficits. We describe a patient who, following an initial presentation at the age of 12 months in keeping with AGS, exhibited a highly atypical relapsing course of neurological symptoms in adulthood with essentially normal neuroimaging. Whole-exome sequencing confirmed a pathogenic RNASEH2B gene variant consistent with AGS.

Acceleration and plateau: two patterns and outcomes of isolated severe fetal cerebral ventricular dilation.

Objectives: We sought to characterize patterns of dilation in isolated severe fetal ventriculomegaly (ISVM) and investigate their value in predicting obstetrical and postnatal outcomes.

Methods: This is a retrospective cohort study. ISVM was defined as a sonographic cerebral ventricle atrial with width ≥15 mm in the absence of additional cerebral or other anatomic anomalies.

Intracranial calcifications and dystonia associated with a novel deletion of chromosome 8p11.2 encompassing and .

Several genes located within the chromosome 8p11.21 region are associated with movement disorders including and is one of four genes associated with primary familial brain calcification, a syndrome that also includes movement disorders, cognitive decline and psychiatric issues. is associated with dystonia type 6, a dominantly inherited dystonia with variable expression.

SCN8A Epileptic Encephalopathy: Detection of Fetal Seizures Guides Multidisciplinary Approach to Diagnosis and Treatment.

Background: SCN8A mutations are rare and cause a phenotypically heterogeneous early onset epilepsy known as early infantile epileptic encephalopathy type 13 (EIEE13, OMIM #614558). There are currently no clear genotype-phenotype correlations to help guide patient counseling and management.

Patient Description: We describe a patient with EIEE13 (de novo heterozygous pathogenic mutation in SCN8A - p.

Leukodystrophies.

Leukodystrophies are heritable disorders primarily affecting the white matter of the central nervous system. They are clinically characterized by spasticity, optic atrophy, and ataxia. These are a heterogeneous group of disorders, including hypomyelinating disorders and demyelinating disorders due to abnormal accumulations.

Gait Disturbance as the Presenting Symptom in Young Children With Anti-NMDA Receptor Encephalitis.

This case series demonstrates a novel clinical phenotype of gait disturbance as an initial symptom in children <3 years old with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Anti-NMDAR encephalitis is one of the most common causes of encephalitis in children, more common than any of the viral encephalitides and the second most common autoimmune cause after acute disseminated encephalomyelitis. Anti-NMDAR encephalitis in children often presents with disrupted speech and sleep patterns followed by progression to motor dysfunction, dyskinesias, and seizures.

Novel KIF7 missense substitutions in two patients presenting with multiple malformations and features of acrocallosal syndrome.

We present two children who both had two missense mutations in the Kinesin Family Member 7 (KIF7) gene. A seven year old female with severe developmental delays, failure to thrive and growth retardation, infantile spasms, a cardiac vascular ring and right-sided aortic arch, imperforate anus, hydronephrosis with a right renal cyst, syndactyly and abnormal white matter was a compound heterozygote for c.3365C > G, predicting p.

The ketogenic diet: uses in epilepsy and other neurologic illnesses.

The ketogenic diet is well established as therapy for intractable epilepsy. It should be considered first-line therapy in glucose transporter type 1 and pyruvate dehydrogenase deficiency. It should be considered early in the treatment of Dravet syndrome and myoclonic-astatic epilepsy (Doose syndrome).