Tests
1st tests to order
clinical diagnosis
Test
No tests are usually necessary. Diagnosis can be made on the history and physical examination alone, but, where available, unscheduled DNA synthesis testing and 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
Tests to consider
unscheduled DNA synthesis
genetic testing
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 preselected genes can be tested on one platform.[23]
If there are existing genetic test results, do not order a duplicate test unless there is uncertainty about the existing result, for example, the result is inconsistent with the patient’s clinical presentation or the test methodology has changed.[32]
Prenatal 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.[33]
Result
identification of biallelic pathogenic variants in one of the causative genes for XP
comprehensive genomic testing
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 analyzed.[34]
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.[34]
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 exam.[23]
If there are existing genetic test results, do not order a duplicate test unless there is uncertainty about the existing result, for example, the result is inconsistent with the patient’s clinical presentation or the test methodology has changed.[32]
Result
identification of biallelic pathogenic variants in one of the causative genes
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