Investigations

1st investigations to order

clinical diagnosis

Test
Result
Test

No tests are usually necessary. Diagnosis can be made on the history and physical examination alone, but, where available, unscheduled DNA synthesis and testing genetic testing confirm the diagnosis and allow subtyping.[12]​

Result

features of XP include severe and exaggerated sunburn with minimal sun exposure or with extensive freckle-like skin lesions (lentigines) in sun-exposed areas typically in children <2 years; in adults, numerous premalignant or malignant skin cancers are seen

Investigations to consider

unscheduled DNA synthesis

Test
Result
Test

Unscheduled DNA synthesis (UDS) in cultured skin fibroblasts measures unscheduled DNA synthesis after UV irradiation.[2]

UDS decreases to <50% of normal cells, except in the XPV subtype in which UDS is more than 70%.[2]

Result

reduced DNA synthesis

genetic testing

Test
Result
Test

An XP multigene panel will search for genes associated with the various subtypes of XP (XPA, XPB [ERCC3], XPC, XPD [ERCC2], XPE [DDB2], XPF [ERCC4], XPG [ERCC5], XPV [POLH]) as well as for genes associated with conditions that are differential diagnoses.[23]​

The clinician is required to have an idea of which genes are likely to be present.[23]​ 

Traditionally, serial single-gene testing was used and can still be done, but multigene testing is preferred as pre-selected genes can be tested on one platform.[23]​

Antenatal diagnosis may be considered and discussed if there is a family history of XP. This can be carried out by DNA testing of cells or fluid obtained from the pregnant mother during chorionic villus sampling or amniocentesis.[32]

Result

identification of biallelic pathogenic variants in one of the causative genes for XP

comprehensive genomic testing

Test
Result
Test

This includes exome sequencing or genome sequencing.

In exome sequencing, the sequence of all protein-coding nuclear genes in the genome are identified and analysed.[33]​ 

While genome sequencing provides more even coverage of the genome and protein coding regions, there is a lower sequencing depth at a higher cost per sample.[33]​ 

Comprehensive genomic testing rather than gene-targeted testing is likely to be requested when the diagnosis of XP has not already been considered from the clinical history and examination.[23]

Result

identification of biallelic pathogenic variants in one of the causative genes

Use of this content is subject to our disclaimer