The severity of the neurological abnormalities in Japanese patients in this group correlates with the sites of nonsense mutations in the XP-A gene. 1516 For example, XP-A is the most severe form, and some of this group have the De Sanctis–Cacchione syndrome (discussed previously). 1515 These different complementation groups have different clinical correlations, including differing susceptibility to the various cutaneous tumors. 1488,1512–1514 These XP groups can be differentiated by using a set of recombinant adenoviruses-which appears to be a convenient and accurate diagnostic method. 1488,1510 Seven of these groups (labeled A–G) have deficient excision repair of ultraviolet radiation-induced DNA damage (particularly nucleotide excision repair), 1511 whereas in one (the so-called XP variant) there is defective ability to convert newly synthesized DNA from low to high molecular weight after UV irradiation (postreplication repair). There is genetic heterogeneity with at least nine different groups recognized by somatic cell fusion studies-so-called complementation groups. 1488 Prenatal diagnosis of xeroderma pigmentosum can be made by an analysis of DNA repair in cells cultured from the amniotic fluid of women at risk.
XERODERMA PIGMENTOSUM PDF SKIN
1508 They are asymptomatic, although there is one report of an increased incidence of malignant skin tumors in these individuals. 1506,1507 Until recently, heterozygotes could not be reliably demonstrated in the laboratory. 1488 There is a high incidence of consanguinity. Xeroderma pigmentosum involves both sexes and all races with an incidence of 1 in 250,000 and a gene frequency of 1 in 200. 1504 Unexpected findings include pyogenic granulomas, desmoplastic melanomas, and multinodular thyroid. 1106,1503 Immunological abnormalities have been present in some patients.
1498 The development of the cutaneous lesions can be retarded by protection from the sun from birth. Skin tumors, which include solar keratoses, cutaneous horns, keratoacanthomas, squamous and basal cell carcinomas, basosquamous carcinoma, atypical fibroxanthoma, 1501 malignant melanomas, 1502 and angiomas, may develop in late childhood patients may ultimately die from the consequences of their tumors. Later, there is dry, scaly skin (xerosis) with poikilodermatous features. 1500 Pigmentation often develops on the palms and soles and mucous membranes. The earliest changes in xeroderma pigmentosum usually develop before the age of 2 years with a severe sunburn reaction and the development of multiple freckles with variable intensity of melanin pigmentation and interspersed hypopigmented macules. 1497 Neurological abnormalities are present in up to 20%, 1498 and these are most severe in the De Sanctis–Cacchione syndrome (microcephaly, dwarfism, choreoathetosis, and mental deficiency OMIM 278800), 1488,1490,1499 which in most cases is associated with the xeroderma pigmentosum group A (XP-A) variant of xeroderma pigmentosum. 1488–1496 Dermoscopy has been used to monitor skin lesions in this condition. Xeroderma pigmentosum (XP) is a rare, autosomal recessive genodermatosis characterized by deficient DNA repair, photophobia, severe solar sensitivity, cutaneous pigmentary changes, xerosis, and the early development of mucocutaneous and ocular cancers, particularly in sun-exposed areas. Patterson MD, FACP, FAAD, in Weedon's Skin Pathology, 2021 Xeroderma Pigmentosum
The results suggest that effective DNA repair is required to maintain the functional integrity of the human nervous system by preventing premature death of neurons.James W. The UV sensitivities of strains from each member of a sibling pair with xeroderma pigmentosum were identical, indicating that UV sensitivity of xeroderma pigmentosum strains is determined by the patient's inherited DNA repair defect. The most sensitive strains were derived from patients who had an early onset of neurological abnormalities less sensitive strains were from patients with a later onset and the most resistant strains were from patients without neurological abnormalities. Sensitivity to ultraviolet radiation of 24 xeroderma pigmentosum fibroblast strains was studied in vitro by measuring each strain's ability to divide and form colonies after irradiation. All xeroderma pigmentosum patients develop premature aging of sun-exposed skin, and some develop neurological abnormalities due to premature death of nerve cells.
Xeroderma pigmentosum is an autosomal recessive disease in which DNA repair processes are defective.
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