RTN2 deficiency results in an autosomal recessive distal motor neuropathy with lower limb spasticity.

Heterozygous RTN2 variants have been previously identified in a limited cohort of families affected by autosomal dominant spastic paraplegia (SPG12-OMIM:604805) with a variable age of onset. Nevertheless, the definitive validity of SPG12 remains to be confidently confirmed due to the scarcity of supporting evidence. In this study, we identified and validated seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven consanguineous families with distal hereditary motor neuropathy (dHMN) using exome, genome and Sanger sequencing coupled with deep-phenotyping. All affected individuals (seven males and seven females, aged 9-50 years) exhibited weakness in the distal upper and lower limbs, lower limb spasticity and hyperreflexia, with onset in the first decade of life. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography. Despite a slowly progressive disease course, all patients remained ambulatory over a mean disease duration of 19.71 ± 13.70 years. Characterization of Caenorhabditis elegans RTN2 homologous loss-of-function variants demonstrated morphological and behavioural differences compared with the parental strain. Treatment of the mutant with an endoplasmic/sarcoplasmic reticulum Ca2+ reuptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences, suggesting a potential therapeutic benefit for RTN2-disorder. Despite RTN2 being an endoplasmic reticulum (ER)-resident membrane shaping protein, our analysis of patient fibroblast cells did not find significant alterations in ER structure or the response to ER stress. Our findings delineate a distinct form of autosomal recessive dHMN with pyramidal features associated with RTN2 deficiency. This phenotype shares similarities with SIGMAR1-related dHMN and Silver-like syndromes, providing valuable insights into the clinical spectrum and potential therapeutic strategies for RTN2-related dHMN.

Lung ultrasound in early prediction of bronchopulmonary dysplasia in pre-term babies.

PURPOSE: Bronchopulmonary dysplasia (BPD) is a respiratory morbidity related to prematurity. Early prediction of BPD allows the selection of patients who would benefit from new therapies. Lung ultrasound (LUS) is a non-invasive diagnostic tool that has proven to be reliable for many neonatal diseases recently. The study aimed to detect the role of LUS in predicting BPD at days 7 and 14 of life in preterm babies. METHODS: This was a prospective cohort study that included 95 preterm babies ≤ 34 weeks. Lung ultrasounds were performed on days 7 and 14 of life. RESULTS: The mean gestational age of the studied neonates was 30.25 ± 2.21 weeks. The mean birth weight was 1347.66 ± 432.14 gm. Patients who developed BPD had statistically significantly higher LUS scores on both days 7 and 14 of life. At first examination, a LUS score > 8 showed a sensitivity of 83.33% and a specificity of 60.87%, whereas at follow-up, a LUS score > 8 showed a sensitivity of 76.39% and a specificity of 82.61%. The multivariate logistic regression analysis shows that the most important factors associated with BPD were gestational age ≤ 30 weeks, LUS score at first examination > 8, platelets ≤ 245 × 109/L, segment neutrophils ≤ 42%, and CRP > 5 mg/l. CONCLUSIONS: The LUS score predicts BPD at 7 and 14 days of life. LUS scores increased with increasing BPD severity. LUS score > 8 was an independent factor in the prediction of BPD.

Role of transcranial Doppler in assessment of cerebral blood flow in full term neonates with extreme unconjugated hyperbilirubinemia.

PURPOSE: To evaluate the difference in cerebral blood flow in neonates with and without extreme unconjugated hyperbilirubinemia. METHODS: Transcranial Doppler parameters of 26 full term newborns with extreme unconjugated hyperbilirubinemia (UCH) were compared to 13 postnatal age and sex matched normal healthy neonates serving as controls. Resistance index (RI), pulsatility index (PI) and peak systolic velocity (PSV) were measured in the middle cerebral, internal carotid and posterior cerebral arteries on both sides by transcranial color Doppler ultrasound. RESULTS: An increase in cerebral blood flow (decreased RI, PI and increased PSV) was observed in the extreme unconjugated hyperbilirubinemia (UCH) group. There was positive correlation between total serum bilirubin level and peak systolic velocity and vice versa with resistivity and pulsatility indices. Eight neonates developed clinical features of acute bilirubin encephalopathy and showed significantly increased peak systolic velocity in the right middle cerebral artery compared to those with normal outcome. Resistivity index and pulsatility index were lower in patients managed by exchange transfusion compared to those managed with phototherapy. CONCLUSION: An increase in cerebral blood flow was observed in neonates with UCH compared to those without hyperbilirubinemia. By assessing the cerebral blood flow velocity, resistivity index (RI), and pulsatility index (PI) of particular intracranial arteries, the transcranial Doppler can identify the at-risk neonates, for development of neurological affliction in extreme unconjugated hyperbilirubinemia.