DeCure for Xeroderma pigmentosum group C

In a 1994 study of 29 Japanese xeroderma pigmentosum group A patients, 25 (86%) carried a homozygous splicing mutation at the junction of intron 3 and exon 4. Those patients developed severe skin manifestations from early infancy and severe progressive neurologic abnormalities including sensorineural hearing impairment, brain atrophy, mental retardation, areflexia, and ataxia. Four patients were heterozygous for that splicing mutation; at least three of them showed milder skin and neurologic symptoms. Two patients (identical twins) were compound heterozygotes for the intron 3 splicing mutation and a nonsense mutation in exon 6. One patient had the splicing mutation plus a previously unreported mutation at the last codon of exon 5. The authors concluded that different genetic alterations in the XPA gene may produce different clinical features.

A 2016 case series of 11 xeroderma pigmentosum patients with head and neck cutaneous malignancies reported a mean age of 32 years (range 10–43; 4 males, 7 females). Squamous cell carcinoma was the most common tumour type (6 patients), and the orbital region the most common location (4 patients). Free tissue transfer was the most frequent surgical intervention (4 patients). The average number of surgical procedures per patient was 5.5 (range 1–25). Six patients were siblings, five had local recurrences, and one was lost to follow-up. The authors stated that no definitive treatment algorithm exists and that early surgical intervention with close follow-up remains the gold standard because of rapid tumour growth and frequent recurrence.

A 2022 literature review of eight articles described xeroderma pigmentosum as an autosomal recessive disease subdivided into seven groups with defects in nucleotide excision repair and one group with a defect in DNA polymerase. The review noted that clinical severity depends on the mutation and the type and intensity of ultraviolet light exposure, and that the disease can affect skin, nervous system, or both, and can also cause internal tumours. Diagnosis is clinical; molecular tests to evaluate DNA synthesis in sun-exposed cells can be performed. The review stated that sunlight deprivation from childhood is the most used therapeutic strategy and that other management approaches are still being studied. The authors concluded that xeroderma pigmentosum is difficult to control, diagnose, and manage, and that further studies and universal access to early diagnostic methods are needed.

What remains missing is a definitive treatment algorithm, any proven systemic therapy, and prospective trials that stratify patients by complementation group or specific mutation. The 2016 series had no control group and was limited to surgical outcomes. The 2022 review found no new therapeutic strategies beyond sun avoidance. No study addressed drug repurposing or molecularly targeted intervention for xeroderma pigmentosum group C specifically.