Since the advent of whole genome sequencing, more than 100 gene variations have been implicated in hereditary neuropathies. Variation in the AHNAK2 gene as a cause for polyneuropathy has been briefly described, for which the mutation was linked to a case of autosomal recessive Charcot-Marie-Tooth. There is otherwise little information about the presentation of this polyneuropathy along with many other hereditary polyneuropathies that have been recently identified. Here, we describe a patient with polyneuropathy found to have homozygous deletions in the AHNAK2 gene.

The patient is a 54-year-old female with sarcoidosis without neurological involvement who presented with 15 years of progressive distal extremity weakness and length-dependent sensory loss to all modalities. EMG showed severe, axonal sensorimotor polyneuropathy with some features of demyelination. She underwent an extensive workup with serum testing, sural nerve biopsy, lumbar puncture and comprehensive genetic panel. Multiple courses of immunotherapy yielded no alleviation in symptoms. Workup was ultimately revealing for homozygous deletions in the AHNAK2 gene on whole genomic sequencing and supportive treatment was pursued. 

Individuals with homozygous deletions in AHNAK2 may present with profoundly disabling axonal polyneuropathy. This case emphasizes that hereditary neuropathies should be considered in any patient with evidence of polyneuropathy, especially if workup for other reversible causes of neuropathy is unremarkable and symptoms are refractory to immunotherapy. Whole genome sequencing is an option for further genetic evaluation if the initial comprehensive genetic panel is negative. Identifying and describing genetic causes of neuropathy with genomic sequencing at a greater volume may aid future research in the development of therapies and provide patients with clear answers regarding their disabling disease.