De novo truncating NOVA2 variants affect alternative splicing and lead to heterogeneous neurodevelopmental phenotypes.

Alternative splicing (AS) is crucial for cell-type-specific gene transcription and plays a critical role in neuronal differentiation and synaptic plasticity. De novo frameshift variants in NOVA2, encoding a neuron-specific key splicing factor, have been recently associated with a new neurodevelopmental disorder (NDD) with hypotonia, neurological features, and brain abnormalities. We investigated eight unrelated individuals by exome sequencing (ES) and identified seven novel pathogenic NOVA2 variants, including two with a novel localization at the KH1 and KH3 domains.

Onasemnogene abeparvovec in spinal muscular atrophy: an Australian experience of safety and efficacy.

Objective: To provide a greater understanding of the tolerability, safety and clinical outcomes of onasemnogene abeparvovec in real-world practice, in a broad population of infants with spinal muscular atrophy (SMA).

Methods: A prospective cohort study of children with SMA treated with onasemnogene abeparvovec at Sydney Children's Hospital Network, Australia was conducted from August 2019 to November 2021. Safety outcomes included clinical and laboratory evaluations.

Mutations disrupting neuritogenesis genes confer risk for cerebral palsy.

In addition to commonly associated environmental factors, genomic factors may cause cerebral palsy. We performed whole-exome sequencing of 250 parent-offspring trios, and observed enrichment of damaging de novo mutations in cerebral palsy cases. Eight genes had multiple damaging de novo mutations; of these, two (TUBA1A and CTNNB1) met genome-wide significance.

Definition and diagnosis of cerebral palsy in genetic studies: a systematic review.

Aim: To conduct a systematic review of phenotypic definition and case ascertainment in published genetic studies of cerebral palsy (CP) to inform guidelines for the reporting of such studies.

Method: Inclusion criteria comprised genetic studies of candidate genes, with CP as the outcome, published between 1990 and 2019 in the PubMed, Embase, and BIOSIS Citation Index databases.

Results: Fifty-seven studies met the inclusion criteria.

Recurrent TTN metatranscript-only c.39974-11T>G splice variant associated with autosomal recessive arthrogryposis multiplex congenita and myopathy.

We present eight families with arthrogryposis multiplex congenita and myopathy bearing a TTN intron 213 extended splice-site variant (NM_001267550.1:c.39974-11T>G), inherited in trans with a second pathogenic TTN variant.

Cisapride treatment for gastro-oesophageal reflux in children.

Background: Gastro-oesophageal reflux (GOR) is common and usually self-limiting in infants. Cisapride, a pro-kinetic agent, was commonly prescribed until reports of possible serious adverse events were associated with its use.

Objectives: To determine the effectiveness of cisapride versus placebo or non-surgical treatments for symptoms of GOR.

High-dose riboflavin for migraine prophylaxis in children: a double-blind, randomized, placebo-controlled trial.

This is the first study to evaluate the efficacy of riboflavin for migraine prophylaxis in children. This was a randomized, double-blind study of riboflavin (200 mg daily) versus placebo in 48 children. The primary efficacy measure was the number of patients achieving a 50% or greater reduction in the number of migraine attacks per 4 weeks.

Severe cerebellitis following methadone poisoning.

We report a 3-year-old girl with an unusual presentation of cerebellitis following ingestion of methadone. CT showed diffuse symmetrical swelling and oedema of the cerebellum resulting in compression of the fourth ventricle and hydrocephalus. The changes were confirmed on MRI with the addition of watershed injuries.

Pharyngeal-cervical-brachial variant Guillain-Barré syndrome in a child.

The pharyngeal-cervical-brachial variant of Guillain-Barré syndrome is uncommon but well recognized in the adult literature. Patients have weakness in a pharyngeal-cervical-brachial distribution with relative lower limb sparing. We describe a 12-year-old boy with predominantly pharyngeal-cervical-brachial weakness and subsequent respiratory failure.