ABD Genodermatoses and Nevi 3 — Questions and Answers
Question 1: Xeroderma pigmentosum results from a defect in which DNA repair pathway?
- Nucleotide excision repair (Correct answer)
- Mismatch repair
- Base excision repair
- Homologous recombination
Correct answer: Nucleotide excision repair
Xeroderma pigmentosum is caused by defective nucleotide excision repair, impairing removal of UV-induced pyrimidine dimers.
Question 2: Patients with xeroderma pigmentosum have a markedly increased risk of what cutaneous complication?
- Early skin cancers on sun-exposed skin (Correct answer)
- Recurrent bacterial abscesses
- Blistering with minor trauma
- Diffuse alopecia
Correct answer: Early skin cancers on sun-exposed skin
Impaired repair of UV damage leads to numerous early basal cell carcinomas, squamous cell carcinomas, and melanomas.
Question 3: Incontinentia pigmenti follows which inheritance pattern and is usually lethal in males?
- X-linked dominant (Correct answer)
- Autosomal recessive
- Autosomal dominant
- Mitochondrial
Correct answer: X-linked dominant
Incontinentia pigmenti (IKBKG/NEMO mutation) is X-linked dominant and typically lethal in affected males in utero.
Question 4: The four sequential stages of incontinentia pigmenti (vesicular, verrucous, hyperpigmented, hypopigmented) follow what distribution?
- Lines of Blaschko (Correct answer)
- Dermatomes
- Langer lines
- Photodistribution
Correct answer: Lines of Blaschko
The cutaneous lesions of incontinentia pigmenti evolve along the lines of Blaschko reflecting mosaicism.
Question 5: A port-wine stain in the V1 trigeminal distribution with leptomeningeal angiomatosis suggests which syndrome?
- Sturge-Weber syndrome (Correct answer)
- Klippel-Trenaunay syndrome
- Parkes-Weber syndrome
- Ataxia-telangiectasia
Correct answer: Sturge-Weber syndrome
Sturge-Weber syndrome combines a facial capillary malformation (port-wine stain) with ipsilateral leptomeningeal and ocular vascular anomalies.
Question 6: Sturge-Weber syndrome and isolated port-wine stains are associated with somatic mosaic mutations in which gene?
- GNAQ (Correct answer)
- GNAS
- AKT1
- RASA1
Correct answer: GNAQ
Somatic activating GNAQ (p.R183Q) mutations underlie both Sturge-Weber syndrome and nonsyndromic port-wine stains.
Question 7: Epidermolysis bullosa simplex most commonly results from mutations in which structural proteins?
- Keratins 5 and 14 (Correct answer)
- Type VII collagen
- Laminin-332
- Type XVII collagen
Correct answer: Keratins 5 and 14
EB simplex is usually caused by mutations in keratin 5 or keratin 14 within basal keratinocytes, producing intraepidermal cleavage.
ABD Genodermatoses and Nevi 3
Xeroderma pigmentosum results from a defect in which DNA repair pathway?