Xeroderma pigmentosum (XP) is caused by defective nucleotide excision repair (NER). Which XP complementation group has the highest cancer risk and is also associated with neurological manifestations?

• A XP-A — severe form with marked neurological involvement (De Sanctis-Cacchione syndrome) ✓
• B XP-C — most common worldwide, no neurological features
• C XP-V (variant) — defective translesion synthesis, no neurological features
• D XP-D — mild form, exclusively skin tumors

Explanation

XP complementation group A (XPA) represents the most severe classic form with the greatest cancer predisposition and neurological involvement. XP-A patients develop De Sanctis-Cacchione syndrome when severe neurological features are present: progressive neurodegeneration, microcephaly, choreoathetosis, hearing loss, and growth retardation. The XPA protein is essential for both global genome NER and transcription-coupled NER. XP-C is the most common complementation group but lacks neurological features. XP-V (variant) has normal NER but defective translesion synthesis polymerase eta.

Reference: Neena Khanna Illustrated Synopsis of Dermatology & STD, 6th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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