Sixteen Finnish patients with xeroderma pigmentosum (XP) were followed for up to 23 years, and their neurological symptoms and course determined in a study at Turku University Central Hospital, Finland; Erasmus University, Rotterdam, The Netherlands; University of Brighton, and University of Sussex, UK. Severe sunburn with minimal sun exposure in early infancy was the first sign of the disease in all cases, only 2 cases being diagnosed at that time. XP patients are assigned in 8 complementation groups, XP-A and XP-C being the most common groups in Europe. Neurological symptoms occur most often in XP-A patients. In XP-C patients, skin problems are severe, but neurological symptoms are rare.
Seven of the 16 Finnish patients were classified as XP-A. All had short stature and microcephaly. They developed normally until age 2 years, but neurological and cognitive dysfunction was apparent in childhood, before the age of 8 years. Cerebellar ataxia was recognized before age 4-16 years, followed by sensory motor neuropathy with areflexia, and sensorineural deafness. Cognitive problems were associated with an unusual tendency to weep and to be frightened. In early adulthood, 8 of 11 patients had developed choreoathetoid involuntary movements. Corticospinal involvement appeared in the third decade, progressing to spastic tetraplegia and dysphagia. Two patients in the XP-C group had normal neurological findings, but they developed severe skin and ocular malignancies in pre-school years. The one XP-G patient had sensorineural hearing loss, laryngeal dystonia and peripheral neuropathy. Neurological disease was associated with failure of fibroblasts to recover RNA synthesis following UV irradiation. Dermatological symptoms included freckling, poikiloderma with hyper- and hypo-pigmentation and skin atrophy, in areas exposed to sun. Eye signs included nodular tumors in the eyelids, conjunctivitis, and keratopathy. Seven patients with severe neurological signs died at a median age of 33 years (range, 29-40 years). Cause of death was pneumonia. 
COMMENT. Xeroderma pigmentosum is a rare autosomal recessive disease that presents in early childhood with unusual skin sensitivity to sun exposure. Dermatological manifestations are complicated in later childhood by progressive neurological, cognitive and ocular manifestations. Patients are classified by complementation analysis in 8 groups, some (group A) being particularly susceptible to neurological symptoms. Early diagnosis and protection from exposure to sunlight result in improved prognosis with minimal skin problems and slower neurological deterioration. UV penetrates only the skin, and the nature of the DNA lesion and mechanism of neurological degeneration are not precisely understood. Dr AMR Taylor of the University of Birmingham, UK, comments that the neurodegeneration is most likely related to some form of oxidative damage.