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

Area of Science:

• Genetics
• Neurology
• Dermatology

Background:

• Xeroderma pigmentosum (XP) is a rare genetic disorder characterized by defective DNA repair, leading to high skin cancer rates.
• Neurological degeneration affects approximately 25% of XP patients, with XP-A and XP-D groups most commonly exhibiting these symptoms.

Purpose of the Study:

• To investigate the characteristics of peripheral neuropathy in patients with Xeroderma pigmentosum (XP).
• To compare neurological findings across different XP complementation groups, focusing on XP-A and XP-D.

Main Methods:

• Retrospective review of 33 XP patients evaluated at NIH from 1986 to 2015 with available nerve conduction studies (NCS).
• Correlative analysis of NCS findings with audiological, brain imaging, and neuropsychological assessments.
• Examination of limited neuropathology in XP-A and XP-D patients.

Main Results:

• Peripheral neuropathy was identified in 78% of XP-A patients (sensorimotor) and 50% of XP-D patients (sensory only).
• Nerve conduction study amplitudes correlated with hearing loss, brain imaging severity, and IQ in XP-A and XP-D groups.
• Sensorineural hearing loss progression appeared faster than NCS changes in follow-up studies.

Conclusions:

• XP-A and XP-D patients exhibit different neuropathy types (sensorimotor vs. sensory) despite similar brain and hearing abnormalities.
• Sensorineural hearing loss may precede detectable nerve conduction abnormalities, serving as an early indicator for peripheral neuropathy development in XP.