Mutations in LNPK, Encoding the Endoplasmic Reticulum Junction Stabilizer Lunapark, Cause a Recessive Neurodevelopmental Syndrome.

The dynamic shape of the endoplasmic reticulum (ER) is a reflection of its wide variety of critical cell biological functions. Consequently, perturbation of ER-shaping proteins can cause a range of human phenotypes. Here, we describe three affected children (from two consanguineous families) who carry homozygous loss-of-function mutations in LNPK (previously known as KIAA1715); this gene encodes lunapark, which is proposed to serve as a curvature-stabilizing protein within tubular three-way junctions of the ER. All individuals presented with severe psychomotor delay, intellectual disability, hypotonia, epilepsy, and corpus callosum hypoplasia, and two of three showed mild cerebellar hypoplasia and atrophy. Consistent with a proposed role in neurodevelopmental disease, LNPK was expressed during brain development in humans and mice and was present in neurite-like processes in differentiating human neural progenitor cells. Affected cells showed the absence of full-length lunapark, aberrant ER structures, and increased luminal mass density. Together, our results implicate the ER junction stabilizer lunapark in establishing the corpus callosum.

Spectrum of Electroencephalography Findings in Newly Diagnosed Epilepsy.

Background Epilepsy is a neurological disorder that presents with recurrent seizures associated with erratic brain activity which can be measured through EEG in addition to other neurological investigations. However, EEG may show abnormal patterns and waveforms while the patient is having a seizure which is crucial for making an accurate diagnosis. Objective This study aims to evaluate the spectrum of EEG findings in newly diagnosed epileptic patients as part of a neurological investigation. Material and methods This cross-sectional study was carried out at the Department of Paediatric Neurology, the Children's Hospital, and the Institute of Child Health, Lahore for six months. A sample of 122 patients was enrolled in this study with an age range of >1 month and <18 years, with a diagnosis of epilepsy based upon ≥2 unprovoked seizures that occurred ≥ 24 hours apart. After obtaining informed consent from the patients, a one-time EEG was carried out and details were noted such as type and frequency of the discharge, site of maximum amplitude, paroxysm morphology, and onset and offset (focal/generalized) of the discharges. The data was analyzed using SPSS v.25 (IBM SPSS Statistics for Windows, Armonk, NY). Results The mean age of children enrolled in this study was 5.58 ± 3.46 years. There were 70 (57.4%) males and 52 (42.6%) females. The mean age at the onset of seizures was 4.85 ± 3.16 years. Out of 122 children, focal onset aware epilepsy type was noted in 8 cases, focal onset impaired awareness was noted in 19 cases and generalized onset motor type of epilepsy was noted in 95 cases. Furthermore, EEG findings were normal in 41 (33.61%) patients; however, 81 (66.39%) EEG findings of the patients place them in the abnormal range. On EEG, paroxysm morphology was typical in 78 (96.3%) patients while atypical in 3 (3.7%) patients. Discharge spectrum was generalized in 46 (56.8%) patients, localized in 19 (23.5%) patients, bilateral independent in 1 (1.2%) patient and multifocal in 15 (18.5%) patients. Discharge pattern was periodic in seven (8.6%) cases, rhythmic delta activity was noted in 4 (4.9%) cases, spike and wave pattern was noted in 68 (84.0%) cases and sharp and wave pattern was observed in 36 (44.4%) patients. Conclusion Our study concluded that EEG findings were abnormal in 81 (66.39%) patients. Thus to make the recommendations locally and nationally, we observed that EEG can highlight the abnormal pattern and discharges in newly diagnosed individuals with epilepsy. Our findings could be instrumental to identify the type of EEG discharges in a timely fashion while making diagnoses and treatment plan protocols accordingly. This study finding recommends the early application of EEG after the presentation of epileptic symptoms by the patient. We further recommend that further similar studies be conducted in multiple tertiary care settings to reach a firm and valuable conclusion.