ABD - American Board of Dermatology Genodermatoses and Nevi Questions and Answers 1 — Questions and Answers
Question 1: A 5-year-old child presents with a history of generalized blistering since birth, particularly over trauma-prone areas. The blisters heal with significant atrophic scarring, milia formation, and have resulted in mitten-like deformities of the hands (pseudosyndactyly). A mutation in the gene encoding which of the following structural proteins is responsible for this condition?
- Laminin 332
- Type VII collagen (Correct answer)
- Keratin 5 or 14
- Plectin
Correct answer: Type VII collagen
The clinical presentation of severe blistering with significant scarring, milia, and pseudosyndactyly is classic for severe recessive dystrophic epidermolysis bullosa (RDEB). This condition is caused by mutations in the COL7A1 gene, which encodes type VII collagen. Type VII collagen is the primary component of anchoring fibrils, which secure the basement membrane to the underlying dermis. Its absence or dysfunction leads to a cleavage plane in the sublamina densa, resulting in the deep, scarring blisters characteristic of DEB. Mutations in keratin 5 or 14 cause EB simplex, laminin 332 mutations cause junctional EB, and plectin mutations cause EB simplex with muscular dystrophy.
Question 2: A 25-year-old Asian woman presents with a congenital, unilateral, patchy blue-gray hyperpigmentation involving the periorbital skin and ipsilateral sclera. In addition to a small increased risk of cutaneous and uveal melanoma, patients with this condition should be screened regularly for which of the following comorbidities?
- Acoustic neuroma
- Seizure disorders
- Glaucoma (Correct answer)
- Dental abnormalities
Correct answer: Glaucoma
This patient's presentation is classic for nevus of Ota (oculodermal melanocytosis). This condition involves dermal melanocytosis in the distribution of the first and second branches of the trigeminal nerve. When the eye is involved (scleral melanocytosis), melanocytes can impede the outflow of aqueous humor, leading to increased intraocular pressure. Consequently, patients with ocular involvement have a significantly increased risk (up to 10%) of developing glaucoma and require regular ophthalmologic screening.
Question 3: Which of the following genodermatoses is characterized by a defect in nucleotide excision repair (NER), leading to extreme photosensitivity, a vastly increased risk of cutaneous malignancies at a young age, and, in some cases, progressive neurologic degeneration?
- Bloom Syndrome
- Rothmund-Thomson Syndrome
- Xeroderma Pigmentosum (Correct answer)
- Cockayne Syndrome
Correct answer: Xeroderma Pigmentosum
Xeroderma pigmentosum (XP) is the quintessential disorder of defective nucleotide excision repair (NER). This autosomal recessive condition results from mutations in genes essential for NER, the primary mechanism for repairing DNA damage caused by ultraviolet (UV) radiation. The inability to repair UV-induced photoproducts leads to extreme photosensitivity, poikiloderma in sun-exposed areas, and a more than 1,000-fold increased risk of skin cancers. Neurologic degeneration is a feature in a subset of XP complementation groups.
Question 4: A newborn is noted to have a solitary, 2x3 cm, hairless, yellow-orange, slightly mamillated plaque on the scalp. The parents are counseled that this lesion may become more verrucous during puberty. While this finding is often isolated, it can be part of Schimmelpenning syndrome, which is characterized by the presence of this nevus and which of the following extracutaneous findings?
- Lisch nodules and axillary freckling
- Skeletal and central nervous system abnormalities (Correct answer)
- Renal angiomyolipomas and cardiac rhabdomyomas
- Gastrointestinal polyps and osteomas
Correct answer: Skeletal and central nervous system abnormalities
The lesion described is a nevus sebaceus. When associated with extracutaneous findings, it constitutes Schimmelpenning syndrome (also known as linear nevus sebaceus syndrome). The most common associated abnormalities involve the central nervous system (CNS) and skeletal system. CNS findings can include intellectual disability and seizures, while skeletal abnormalities may include frontal bossing, bone hypoplasia, and vitamin D-resistant rickets.
Question 5: A 22-year-old male presents with persistent, greasy, crusted papules in a seborrheic distribution. Examination reveals flat-topped, wart-like papules on the dorsum of his hands and distinctive red and white longitudinal bands in his nails with distal V-shaped nicking. This constellation of findings is characteristic of Darier disease, which is caused by a mutation in the gene encoding which protein?
- Filaggrin
- Transglutaminase 1
- SERCA2 calcium pump (Correct answer)
- Connexin 26
Correct answer: SERCA2 calcium pump
Darier disease (keratosis follicularis) is an autosomal dominant disorder of keratinization caused by mutations in the ATP2A2 gene. This gene encodes the sarco/endoplasmic reticulum Ca2+-ATPase isoform 2 (SERCA2), a crucial pump that regulates intracellular calcium levels. Disruption of calcium homeostasis impairs keratinocyte adhesion (leading to acantholysis) and differentiation, resulting in the characteristic clinical and histological findings.
Question 6: A 10-year-old presents with a new, rapidly growing, 0.7 cm, symmetric, dome-shaped, pink papule on her cheek. Histopathology reveals a well-circumscribed, wedge-shaped proliferation of large epithelioid and spindled melanocytes with prominent eosinophilic cytoplasm. Eosinophilic, PAS-positive globules are noted within the epidermis. What is the most likely diagnosis?
- Congenital melanocytic nevus
- Dysplastic nevus
- Nodular melanoma
- Spitz nevus (Correct answer)
Correct answer: Spitz nevus
The clinical picture of a rapidly growing pink nodule in a child, combined with the classic histopathologic features of a symmetric, wedge-shaped proliferation of large spindle and epithelioid melanocytes, is characteristic of a Spitz nevus. The eosinophilic, PAS-positive globules described are Kamino bodies, which are a highly characteristic, though not entirely pathognomonic, feature of Spitz nevi.
ABD - American Board of Dermatology Genodermatoses and Nevi Questions and Answers 1
A 5-year-old child presents with a history of generalized blistering since birth, particularly over trauma-prone areas.
The blisters heal with significant atrophic scarring, milia formation, and have resulted in mitten-like deformities of the hands (pseudosyndactyly).
A mutation in the gene encoding which of the following structural proteins is responsible for this condition?