Differences in Peripheral Neuropathy in  Xeroderma Pigmentosum Complementation Groups A and D

Abstract

BACKGROUNDXeroderma 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. METHODSThis is a retrospective review of patients with XP who were evaluated at NIH from 1986 to 2015 and had nerve conduction studies (NCS). Audiological, brain imaging, neuropsychological assessments were also performed on most of the patients. Limited neuropathology of XP-A and XP-D patients were compared. RESULTSThe 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 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. The severity of the neuropathy correlated with hearing loss. CONCLUSIONSDespite 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 and absent deep tendon reflexes may precede abnormal NCS in XP and therefore serve as valuable clinical indicators of XP patients that will later develop peripheral neuropathy. TRIAL REGISTRATION: Patients were evaluated under clinical protocols, NCT00001813 and NCT00046189, approved by the NIH Institutional Review Boards.