GLRB is the third major gene of effect in hyperekplexia.

Glycinergic neurotransmission is a major inhibitory influence in the CNS and its disruption triggers a paediatric and adult startle disorder, hyperekplexia. The postsynaptic α(1)-subunit (GLRA1) of the inhibitory glycine receptor (GlyR) and the cognate presynaptic glycine transporter (SLC6A5/GlyT2) are well-established genes of effect in hyperekplexia. Nevertheless, 52% of cases (117 from 232) remain gene negative and unexplained. Ligand-gated heteropentameric GlyRs form chloride ion channels that contain the α(1) and ß-subunits (GLRB) in a 2α(1):3ß configuration and they form the predominant population of GlyRs in the postnatal and adult human brain, brainstem and spinal cord. We screened GLRB through 117 GLRA1- and SLC6A5-negative hyperekplexia patients using a multiplex-polymerase chain reaction and Sanger sequencing approach. The screening identified recessive and dominant GLRB variants in 12 unrelated hyperekplexia probands. This primarily yielded homozygous null mutations, with nonsense (n = 3), small indel (n = 1), a large 95 kb deletion (n = 1), frameshifts (n = 1) and one recurrent splicing variant found in four cases. A further three cases were found with two homozygous and one dominant GLRB missense mutations. We provide strong evidence for the pathogenicity of GLRB mutations using splicing assays, deletion mapping, cell-surface biotinylation, expression studies and molecular modelling. This study describes the definitive assignment of GLRB as the third major gene for hyperekplexia and impacts on the genetic stratification and biological causation of this neonatal/paediatric disorder. Driven principally by consanguineous homozygosity of GLRB mutations, the study reveals long-term additive phenotypic outcomes for affected cases such as severe apnoea attacks, learning difficulties and developmental delay.

Backpack palsy: A rare complication of backpack use in children and young adults - A new case report.

Backpack palsy is a well-recognised, albeit rare, complication of carrying backpacks. Although it has been mostly described in cadets during strenuous training, sporadic cases of brachial nerve impairment have been reported in children and young adults. Here we reported the case of a 15-year-old girl who presented with a left-side brachial palsy with axonal denervation of C5C7 motor roots following a school challenge for the Duke of Edinburgh Award. Her symptoms began soon after starting the challenge and included weakness of shoulder abduction and elevation, as well as forearm, wrist and fingers extension. After 6 months of physiotherapy her motor function was completely restored. Backpack palsy can sometimes present in children and young adults. This disorder should be taken in consideration when planning for daily, as well as more challenging, physical activities in these age groups.

Community acquired Panton-Valentine Leukocidin (PVL) positive Methicilin Resistant Staphylococcal aureus cerebral abscess in an 11-month old boy: a case study.

BACKGROUND: Brain abscess are uncommon childhood infection. Brain abscess caused by Panton-Valentine Leukocidin positive Community acquired Methicillin Resistant Staphylococcal aureus have never been reported in the United Kingdom. CASE PRESENTATION: We report a case of a previously well 11-month old boy of Indian origin who developed a parietal lobe abscess from PVL positive CA-MRSA. CONCLUSION: This case is one of the few described cases of brain abscess caused by PVL CA-MRSA in children. The unusual (insidious) presentation, the absence of a clear staphylococcal focus and the unexpected finding of a CA-MRSA in this patient highlight the challenges of managing such cases in clinical settings and the potential future risk to public health.