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Progressive ataxia associated with scarring skin lesions and vertical gaze palsy
Author(s) -
Ganos Christos,
Biskup Saskia,
Kleinmichel Stefanie,
Zittel Simone,
Schunke Odette,
Gerloff Christian,
Münchau Alexander
Publication year - 2013
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.25363
Subject(s) - gaze , ataxia , palsy , content (measure theory) , physical medicine and rehabilitation , psychology , medicine , neuroscience , computer science , pathology , psychoanalysis , alternative medicine , mathematics , mathematical analysis
Xeroderma pigmentosum (XP) is a rare autosomal-recessive disease (prevalence of 1:200,000 in whites) characterized by hypersensitivity to ultraviolet (UV) radiation because of faulty DNA repair, leading to early-onset recurrent sunburns with cutaneous hyperpigmentation and a 1000-fold increased likelihood of developing dermal and ocular neoplasias, commonly nonmelanoma skin cancer, followed by melanoma. Seven genes (XP A–G) are known to be involved in the process of nucleotide excision repair of UV-induced DNA defects. XP V is involved in the replication process of damaged DNA. More than 20% of XP patients present with neurologic abnormalities, typically ataxia, hyporeflexia, bulbar symptoms, hearing impairment, and severe mental retardation. These typically develop when the aforementioned skin abnormalities are already present. Patients with neurologic symptoms have an earlier mean onset age of cutaneous symptoms (6 months) compared with patients without neurologic symptoms (2 years). Although patients with neurologic abnormalities usually have a more severe cutaneous phenotype, mean survival is similar in both groups, with only 5% of patients surviving beyond the age of 45. Here, we describe 2 adult siblings of Turkish origin (pedigree shown in Fig. 1) with a complex neurological syndrome, distinct skin lesions, and a homozygous mutation in the XP A gene (c.682C>T; p.R228X).