AUSTIN, TEX. – Patients with peripheral neuropathy may benefit from genetic testing to determine of the cause of their neuropathy even if they do not have a family history of the condition, according to new research.
Dr. Sasa Zivkovic
The same research identified more than 80 genetic variants in patients with neuropathy who lacked any other known genetic mutations, potentially representing not-yet-identified pathogenic mutations.
Sasa Zivkovic, MD, PhD, of the University of Pittsburgh Medical Center (UPMC), and associates shared a poster of their findings at the annual meeting of the American Association for Neuromuscular and Electrodiagnostic Medicine.
The researchers conducted next-generation sequencing (NGS) on 85 adult patients with peripheral neuropathy at the UPMC Neuromuscular Clinic during May 2017–Feb. 2019. The targeted NGS panel included 70 genes. The patients, aged 60 years on average, were primarily from Allegheny County, Pa., and had neuropathy either suspected to be hereditary or of unknown etiology.
Among the 19% of patients (n = 16) who tested positive for a known pathogenic mutation, half had Charcot-Marie-Tooth disease type 1A (CMT1A). Two patients – 13% of those with pathogenic variants – had hereditary neuropathy with liability to pressure palsies, and two had CMT1X. The remaining four patients had CMT1B, CMT2B1, CMT2E, and hereditary sensory and autonomic neuropathy mutations.
Another 4% of the overall patient sample (n = 3) had likely pathogenic mutations in genes associated with CMT2S, CMT4C and CMT4F. A third of the patients (32%) tested negative for the full NGS panel, and, comprising the largest proportion of patients, 46% had variants of unknown significance.
“The high occurrence of variants of unknown significance has uncertain significance but some variations may represent unrecognized pathogenic mutations,” the authors noted.
They identified 81 of these variants, with the DST, PLEKHG5, and SPG11 genes most commonly affected, each found in six patients. Four patients had a variant in the next most commonly affected gene, SBF2. The following variants occurred in three people each: BICD2, NEFL3, PRX, SCN11A, SCN9A, SLC52A2, and WNK1.
Among the 73 patients who underwent electrodiagnostic testing, 44 had sporadic axonal neuropathy, 17 had sporadic demyelinating neuropathy, and 11 had mixed neuropathies; the 1 remaining patient was not accounted for. Positive genetic testing occurred in a third (32%) of those with familial neuropathy (n = 28) and in 12% of those with sporadic neuropathy (n = 57).
No external funding was noted, and the authors had no disclosures.
SOURCE: Zivkovic S et al. AANEM 2019. Abstract 160. Targeted genetic testing in the evaluation of neuropathy .