Differences in peripheral neuropathy in xeroderma pigmentosum complementation groups A and D as evaluated by nerve conduction studies

Tanya J Lehky; Paul Sackstein; Deborah Tamura; Martha Quezado; Tianxia Wu; Sikandar G Khan; Nicholas J Patronas; Edythe Wiggs; Carmen C Brewer; John J DiGiovanna; Kenneth H Kraemer

doi:10.1186/s12883-021-02414-2

Differences in peripheral neuropathy in xeroderma pigmentosum complementation groups A and D as evaluated by nerve conduction studies

BMC Neurol. 2021 Oct 9;21(1):393. doi: 10.1186/s12883-021-02414-2.

Authors

Affiliations

¹ EMG Section, NINDS, NIH, Bethesda, MD, USA. lehkyt@ninds.nih.gov.
² Laboratory of Cancer Biology and Genetics NCI, NIH, Bethesda, MD, USA.
³ Medstar Georgetown University Hospital, Washington, DC, USA.
⁴ Laboratory of Pathology, NCI, NIH, Bethesda, MD, USA.
⁵ Clinical Trials Unit, NINDS, NIH, Bethesda, MD, USA.
⁶ Radiology and Imaging Sciences, CC, NIH, Bethesda, MD, USA.
⁷ Otolaryngology Branch, NIDCD, NIH, Bethesda, MD, USA.

Abstract

Background: Xeroderma pigmentosum (XP) is a rare autosomal recessive genetic disorder with defective DNA nucleotide excision repair and associated with a high frequency of skin cancer. Approximately 25% of patients develop progressive neurological degeneration. Complementation groups XP-A and XP-D are most frequently associated with neurological disorders.

Design/methods: This is a retrospective review of patients with XP who were evaluated at NIH from 1986 to 2015 and had nerve conduction studies (NCS). In the complementation groups with peripheral neuropathy, further comparisons of the NCS were made with audiological, brain imaging, neuropsychological assessments that were also performed on most of the patients. Limited neuropathology of XP-A and XP-D patients were examined..

Results: The 33 patients had NCS: XP-A (9 patients), XP-C (7 patients), XP-D (10 patients), XP-E (1 patient), XP-V (4 patients), and XP-unknown (2 patients). Peripheral neuropathy based on nerve conduction studies was documented only in two complementation groups: 78% (7/9) of XP-A patients had a sensorimotor neuropathy while 50% (5/10) of XP-D patients had a sensory neuropathy only. Analysis of sural sensory nerve amplitude in both complementation groups XP-A and XP-D correlated with sensorineural hearing loss (SNHL), MRI/CT severity, and Full-scale Intelligence Quotient (IQ). Analysis of fibular motor nerve amplitude in complementation XP-A correlated with SNHL and MRI/CT severity. Limited follow-up studies showed gradual loss of NCS responses compared to an earlier and more rapid progression of the hearing loss.

Conclusions: Despite similar brain imaging and audiological findings patients, XP-A and XP-D complementation groups differ in the type of neuropathy, sensorimotor versus sensory alone. A few cases suggest that sensorineural hearing loss may precede abnormal NCS in XP and therefore serve as valuable clinical indicators of XP patients that will later develop peripheral neuropathy.

Keywords: DNA repair; Neurodegeneration; Peripheral neuropathy; Sensorineural hearing loss; Xeroderma pigmentosum.

MeSH terms

DNA Repair
Humans
Neural Conduction
Peripheral Nervous System Diseases* / diagnostic imaging
Peripheral Nervous System Diseases* / genetics
Retrospective Studies
Xeroderma Pigmentosum* / complications
Xeroderma Pigmentosum* / genetics