Blended Hereditary Neuropathy Phenotype Caused by Biallelic PRX and SCN9A Variants: A Case Report.

INTRODUCTION

Inherited neuropathies are genetically heterogeneous, and with the increasing use of next-generation sequencing, multilocus pathogenic variants are now being recognized more frequently, particularly in populations with high consanguinity. We report the first known coexistence of PRX- and SCN9A-related disorders in the same patient.

CASE PRESENTATION: A 17-month-old girl presented with walking difficulties, profound insensitivity to pain, self-mutilation, finger tissue loss, and chronic ulcerations. Physical examination revealed dentition abnormality, distal phalanx loss, bilateral genu recurvatum, and reflex loss. Imaging revealed osteomyelitis and chronic fractures, while electrophysiology revealed severe demyelinating neuropathy. Genetic testing identified homozygous pathogenic variants in the PRX NM_181882.3:c.1390C>T p.(Arg464Ter) and SCN9A NM_002977.3:c.3143_3154delinsA p.(Ile1048LysfsTer13) genes, which were confirmed by Sanger sequencing.

CONCLUSION

Coexisting autosomal recessive disorders can produce blended phenotypes beyond classical disease expectations. In populations where consanguineous marriages are common, multilocus pathogenic variants should be considered, and comprehensive genomic testing is recommended.