Laboratory Studies
No consistent routine laboratory abnormalities are present in xeroderma pigmentosum patients. The diagnosis of xeroderma pigmentosum can be established with studies performed in specialized laboratories. These studies include cellular hypersensitivity to UV radiation and chromosomal breakage studies, complementation studies, and gene sequencing to identify the specific gene complementation group.
In the cellular hypersensitivity to UV radiation and chromosomal breakage studies, the xeroderma pigmentosum fibroblasts are stressed with different doses of UV radiation. Then, chromosomal breakage is evaluated in at least 100-200 cells, with at least 2 replicates for each dose. The cells from the patient are compared with those from the patient's parents (if possible, as they are obligate heterozygotes for xeroderma pigmentosum). Cells from unrelated healthy individuals are used as controls. To eliminate subjectivity, the person evaluating the chromosomal abnormalities is not informed as to which group the slides being examined belong. Prenatal diagnosis of xeroderma pigmentosum can be accomplished using similar chromosomal breakage studies on amniocytes from at-risk fetuses.
The xeroderma pigmentosum complementation groups can be determined using cell-fusion techniques followed by assessment of DNA repair or by gene sequencing.
Prenatal diagnosis is possible by amniocentesis or chorionic villi sampling. Unscheduled DNA synthesis is the classic method for diagnosis. A modified technique using cultivation of both patient and control cells at the same time has also been described. [21] A faster technique is the alkaline comet assay (single-cell gel electrophoresis assay). This method, in addition to being faster, requires fewer cells and does not require radioactivity. [22]
Other Tests
Electroencephalographic findings may be abnormal.
Histologic Findings
The histologic findings of the first stage of the disease include hyperkeratosis and increased melanin pigment (this corresponds to the clinical freckling) in the basal cell layer (not necessarily accompanied by an increase in the numbers of melanocytes). Some rete ridges may be elongated, whereas other rete ridges may be atrophic. These findings may be accompanied by a chronic inflammatory infiltrate in the upper dermis.
In the second stage, atrophy ensues, and the hyperkeratosis and the hyperpigmentation are more marked. Telangiectasia may be prominent. These findings correspond to poikiloderma. In addition, the epidermis may exhibit architectural disorder and atypia, and the dermis may be elastotic. Therefore, the histologic picture might be indistinguishable from that of actinic keratosis (see following image). The histologic appearances of the various tumors that complicate xeroderma pigmentosum are seen in the third stage of xeroderma pigmentosum.
Histologic features of actinic keratosis in an individual with xeroderma pigmentosum. Note the atypia of the keratinocytes and the parakeratosis.
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Face of a toddler with xeroderma pigmentosum, representative of an early stage of the disease. Note the freckling and the scaling. Courtesy of Neil S. Prose, MD, Duke University Medical Center, Durham, North Carolina.
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Back of an adolescent with xeroderma pigmentosum, representing a later stage of the disease. Note the mottled hyperpigmentation and atrophy. Courtesy of Neil S. Prose, MD, Duke University Medical Center, Durham, North Carolina.
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Histologic features of actinic keratosis in an individual with xeroderma pigmentosum. Note the atypia of the keratinocytes and the parakeratosis.
