Characteristics of Xeroderma Pigmentosum in Japan: Lessons From Two Clinical Surveys and Measures for Patient Care

Abstract

Xeroderma pigmentosum (XP) is a rare autosomal recessive hereditary disease caused by deficiency in repair of DNA lesions generated by ultraviolet radiation and other compounds. Patients with XP display pigmentary change and numerous skin cancers in sun‐exposed sites, and some patients show exaggerated severe sunburns even upon minimum sun exposure as well as neurological symptoms. We conducted a nationwide survey for XP since 1980. In Japan, the frequency of the XP complementation group A is the highest, followed by the variant type; while in the Western countries, those of groups C or D are the highest. Regarding skin cancers in XP, basal cell carcinoma was the most frequent cancer that afflicted patients with XP, followed by squamous cell carcinoma, and malignant melanoma. The frequency of these skin cancers in patients with XP has decreased in these 20 years, and the age of onset of developing skin cancers is higher than those previously observed, owing to early diagnosis and education to patients and care takers on strict prevention from sunlight for patients with XP. On the other hand, the effective therapy for neurological XP has not been established yet, and this needs to be done urgently.

Lentigo maligna in a patient with xeroderma pigmentosum, variant type: A case report with dermoscopic findings and review of the literature

“…9 Regarding the frequency of the XP complementation groups, group C or D is the common in western countries, while group A is the highest, followed by the variant type in Japanese population. 10 Compared to the other subgroups, XPV patients have a significantly delayed onset of skin lesions, with milder symptoms and prolonged course of the disease. 3 Xeroderma pigmentosum is rare but appears to be present in every ethnic group with different prevalence; the rate for all groups of XP is estimated as 1:1 000 000 in the USA and Europe and 1:22 000 in Japan.…”

Variant subtype of xeroderma pigmentosum with multiple basal cell carcinomas diagnosed in a Chinese woman

“…As an autosomal recessive genetic disease, XP has various clinical manifestations, among them, the most characteristic feature is patients' predisposition to skin cancers. 16 Overlapping clinical features Dermatoscopy is a noninvasive technique for the diagnosis of skin lesions that helps clinicians differentiate benign from malignant lesions with its higher sensitivity and specificity for skin cancers detection than the naked eye examination. 17 The dermoscopic findings in skin cancers were similar to those previously described in patients not affected by XP.…”

Progressive length‐dependent polyneuropathy in xeroderma pigmentosum group A

“…The severity is different among the complementation groups and XP‐A patients manifest the most severe symptoms 3 . Various neurological symptoms including areflexia, loss of pain sensation, sensory ataxia, microcephaly, intellectual disability, choreoathetosis, cerebellar ataxia, spasticity, and sensorineural deafness are recognized, resulting in death around the age of 30 y, due to complications 2,5‐13 . Thus, neurodegeneration and skin cancer are the major causes of death 2,5‐11 .…”

“…Various neurological symptoms including areflexia, loss of pain sensation, sensory ataxia, microcephaly, intellectual disability, choreoathetosis, cerebellar ataxia, spasticity, and sensorineural deafness are recognized, resulting in death around the age of 30 y, due to complications 2,5‐13 . Thus, neurodegeneration and skin cancer are the major causes of death 2,5‐11 . Although the risk of skin cancer can be reduced in XP patients by rigorous protection from the sun, there is no effective treatment to alter the progression of neurological deterioration 5‐7 …”

“…In Japan, XP‐A accounts for more than half of the XP patients resulting from a founder mutation; these patients develop very severe cutaneous and neurological symptoms 11,14‐17 . In almost 100% of XP‐A patients, both the central nervous system (CNS) and peripheral nervous system (PNS) are impaired 17 .…”