Prevalence of Sensorineural Hearing Loss in Pediatric Patients with Sickle Cell Disease: A Meta-analysis

Objectives: To determine the prevalence of Sensorineural Hearing Loss (SNHL) attributable to Sickle Cell Disease (SCD) in the global pediatric population and to identify factors contributing to its severity. Study Design: Meta-analysis. Methods: We performed a comprehensive literature search for scientific articles in PubMed, Scopus, CINAHL, Web of Science, and the Cochrane Library that reported the incidence of hearing loss in populations under 18 years of age with excluding studies analyzing patients on iron chelation therapy, adults, or those without objective audiological analysis. Results: We identified 138 initial studies with 17 selected for analysis after applying the exclusion criteria. A total of 1,282 SCD patients and 553 controls were included in the meta-analysis. There was a statistically significant increase in the prevalence of SNHL in children with SCD compared to the general population with a cumulative risk ratio of 3.33. Conclusion: This is the first systematic investigation of the relationship between SCD and SNHL in pediatric patients across the globe. The increased prevalence of SNHL in the pediatric SCD population warrants future research into the predictors of SNHL severity and merits routine audiometric monitoring of SCD patients to reduce the social and developmental morbidity of hearing loss at a young age. PROSPERO Registration #: CRD42019132601. Laryngoscope, 2020

Absence of axoglial paranodal junctions in a child with CNTNAP1 mutations, hypomyelination, and arthrogryposis

Leukodystrophies and genetic leukoencephalopathies are a heterogeneous group of heritable disorders that affect the glial-axonal unit. As more patients with unsolved leukodystrophies and genetic leukoencephalopathies undergo next generation sequencing, causative mutations in genes leading to central hypomyelination are being identified. Two such individuals presented with arthrogryposis multiplex congenita, congenital hypomyelinating neuropathy, and central hypomyelination with early respiratory failure. Whole exome sequencing identified biallelic mutations in the CNTNAP1 gene: homozygous c.1163G>C (p.Arg388Pro) and compound heterozygous c.967T>C (p.Cys323Arg) and c.319C>T (p.Arg107*). Sural nerve and quadriceps muscle biopsies demonstrated progressive, severe onion bulb and axonal pathology. By ultrastructural evaluation, septate axoglial paranodal junctions were absent from nodes of Ranvier. Serial brain magnetic resonance images revealed hypomyelination, progressive atrophy, and reduced diffusion in the globus pallidus in both patients. These 2 families illustrate severe progressive peripheral demyelinating neuropathy due to the absence of septate paranodal junctions and central hypomyelination with neurodegeneration in CNTNAP1-associated arthrogryposis multiplex congenita