J Neurosci Rural Pract., official publication of Associacion Ayuda Enfermo Neuroquirurgico (Association for Helping Neurosurgical Sick People)

Purpose: Polyneuritis cranialis (PNC) is a less known regional variant of Guillain-Barré syndrome and has rarely been described in children. Here, we report a case of an adolescent, who became perilously ill following severe acute respiratory syndrome-coronavirus 2 infection. Case report: A 15-year-old boy presented with acute multiple cranial nerve palsies. The presence of GQ1b antibodies and nerve conduction studies confirmed the diagnosis of PNC. The patient was treated with plasmapheresis and intravenous immunoglobulins, but clinical improvement was gradual and very slow. Conclusion: PNC is a rare and severe neurologic condition that can be triggered by coronavirus infection.

Background: Neurodevelopmental disorders (NDDs) are genetically heterogeneous, and exome sequencing (ES) is now a first-line diagnostic tool. However, many patients receive variants of uncertain significance (VUSs) or inherited variants with incomplete penetrance, limiting clinical interpretation. Emerging multi-omics evidence from the literature can support the interpretation of novel and rare variants, helping to refine classification in selected cases. Methods: We assessed 20 patients and their parents referred for genetic testing for NDDs. ES was performed, followed by ACMG/ACGS-based variant classification, segregation analysis, and targeted literature review. Variants were included when deemed plausible contributors to the phenotype by a multidisciplinary team. Gene-level constraint metrics, in silico predictions, and emerging multi-omics evidence from the literature were integrated to support interpretation. Results: Across 18 NDD-associated genes, we identified 20 rare variants: Three pathogenic (P), nine likely pathogenic (LP), and eight VUSs. All P and most LP variants were de novo. Inherited variants, particularly in KMT5B, TANC2, SPTBN1, and CHD4, highlighted challenges related to incomplete penetrance. Two patients had dual molecular diagnoses. Several VUSs were supported by literature-derived transcriptomic, proteomic, or model-system evidence. Conclusions: This cohort underscores ongoing challenges in interpreting VUSs and inherited variants in NDDs. Integrating genomic findings with published multi-omics data enhances variant interpretation, reveals mechanistic insights, and strengthens diagnostic confidence, supporting broader adoption of multi-omics approaches in rare NDD evaluation.