Diagnostic pathway for a patient with sensorineural-vegetative polyneuropathy, anhidrosis, and behavioral disorders – from clinical to genetic

The article presents a description of a clinical case of a 6-year-old child with a progressive complex of neurological and systemic disorders, which included congenital total analgesia and anhidrosis, sensory-autonomic polyneuropathy with episodes of acute paresis, cerebellar ataxia, dysarthria, cognitive deficit, autism spectrum disorders, autoaggression, autonomic crises with postural hypotension, as well as lesions of the musculoskeletal, cardiovascular and endocrine systems. Despite extensive examination, the etiology of the disease remained unclear for a long time. The key finding was the detection of a heterozygous variant of uncertain clinical significance chr14-23534080GA, NM_033400.3, c.1246CT (p.Pro416Ser) in the ZFHX2 gene, associated with the extremely rare Marsili syndrome, using whole-genome sequencing. This case illustrates the challenges in diagnosing rare diseases, describes a unique extended phenotype, and demonstrates the potential role of a new genetic variant in the development of complex multisystem lesions.