Xeroderma Pigmentosum Flashcards
A 5-year-old boy is brought to the pediatrician by his parents for evaluation of multiple skin lesions. They report that the child develops dryness, redness, and blistering even with minimal sun exposure. On examination, there are numerous freckles, hypopigmented and hyperpigmented macules on the face, neck, and arms. There is also a large ulcerated lesion on the nose. The child has mild conjunctival injection but no discharge. Family history reveals that an older sibling died of melanoma at the age of 15. Genetic testing reveals a mutation in a gene responsible for nucleotide excision repair.
What is the most likely diagnosis, and what is the primary preventative intervention for this condition?
A. Albinism, use of protective clothing and sunscreen
B. Xeroderma Pigmentosum, strict sun protection
C. Ataxia-telangiectasia, avoidance of ionizing radiation
D. Hereditary melanoma syndrome, regular dermatologic examinations
E. Cutaneous lupus erythematosus, use of topical steroids
Correct Answer: Xeroderma Pigmentosum, strict sun protection
Explanation: Xeroderma Pigmentosum (XP) is an autosomal recessive disorder caused by defective nucleotide excision repair of UV-induced DNA damage. Patients present with extreme photosensitivity, early freckling, and pigmentary changes in sun-exposed areas. There is a markedly increased risk of early-onset skin cancers such as basal cell carcinoma, squamous cell carcinoma, and melanoma. Prevention focuses on strict sun protection, including UV-blocking clothing, sunscreen, and avoiding direct sunlight. Early recognition and regular dermatologic surveillance are critical to minimizing morbidity and mortality.
Incorrect Answers:
A. Albinism: Albinism involves a defect in melanin synthesis and does not lead to the severe sun damage or increased cancer risk seen in XP.
C. Ataxia-telangiectasia: Although this condition involves a DNA repair defect, it primarily presents with cerebellar ataxia, oculocutaneous telangiectasias, and immunodeficiency, not severe photosensitivity or skin cancer.
D. Hereditary melanoma syndrome: This condition involves familial clustering of melanoma but does not present with extreme photosensitivity or genetic defects in nucleotide excision repair.
E. Cutaneous lupus erythematosus: This autoimmune condition may cause photosensitivity but lacks the genetic basis of XP and the significantly increased early-onset skin cancer risk.
What is the inheritance pattern of Xeroderma Pigmentosum?
Xeroderma Pigmentosum follows an autosomal recessive inheritance pattern.
What is the pathophysiology of Xeroderma Pigmentosum (XP)?
Xeroderma Pigmentosum is an autosomal recessive disorder caused by mutations in nucleotide excision repair (NER) genes, inability to repair DNA pyrimidine dimers during the G1 phase of the cell cycle, leading to defective DNA repair of UV-induced damage.
What is the primary cause of DNA damage in Xeroderma Pigmentosum?
UV radiation from sunlight causes thymine dimers in DNA, which cannot be properly repaired due to defective nucleotide excision repair in XP.
What are the hallmark clinical features of Xeroderma Pigmentosum?
Features include extreme sensitivity to sunlight (photosensitivity), early onset of freckling, dry skin (xerosis), pigmentary changes, and a markedly increased risk of skin cancers.
Solar lentigines, xerosis, and poikiloderma due to repeated exposure to sunlight.
Premalignant lesions (e.g., actinic keratoses) and malignant lesions often develop during early childhood.
What types of skin cancers are common in Xeroderma Pigmentosum?
Patients with XP are at high risk for basal cell carcinoma, squamous cell carcinoma, and malignant melanoma at an early age.
What brain tumors are associated with Xeroderma Pigmentosum?
glioblastomas, medulloblastomas, Schwannomas, and astrocytomas
Are there any pulmonary diseases associated with Xeroderma Pigmentosum?
Yes, lung cancer is a common manifestation.
What are the ocular manifestations of Xeroderma Pigmentosum?
Ocular findings include photophobia, conjunctivitis, corneal ulcerations and opacification, and increased risk of ocular neoplasms due to UV exposure.
ophthalmic examinations every 3–6 months.
What systemic complications can occur in Xeroderma Pigmentosum?
Some patients develop neurological complications, including progressive neurodegeneration, hearing loss, and intellectual disability.
Why is early diagnosis important in Xeroderma Pigmentosum?
Early diagnosis allows for strict UV protection, reducing the risk of skin cancers and delaying or preventing complications.
How is Xeroderma Pigmentosum diagnosed?
Diagnosis is based on clinical features, family history, and genetic tests showing defective nucleotide excision repair or genetic testing for mutations in NER pathway genes.
Cellular testing for defective DNA nucleotide repair from a punch biopsy sample from minimally sun-exposed skin (upper inner arm or buttocks).
What is the treatment and management strategy for Xeroderma Pigmentosum?
Management includes strict sun protection (UV-blocking clothing, sunscreen), regular dermatologic and ophthalmologic evaluations, and early treatment of skin cancers.
What vitamin deficiency is commonly associated with Xeroderma Pigmentosum?
Individuals with xeroderma pigmentosum are at increased risk of vitamin D deficiency due to reduced exposure to UV light. Assess for and treat vitamin D deficiency as indicated.
