This patient is presenting with café-au-lait spots, neurofibromas, and Crowe's sign (freckling in the inguinal and axillary regions). These symptoms are most likely due to a mutated NF-1 (neurofibromin 1) gene.
Neurofibromatosis type I (von Recklinghausen's disease) is an autosomal dominant disorder caused by a mutation in the NF-1 gene on chromosome 17. NF-1 is a tumor-suppressor gene and mutations in this gene produce neuroectodermal tumors in several organs. Presenting symptoms include café-au-lait spots, Crowe's sign, optic gliomas, Lisch nodules, neurofibromas, and pheochromocytomas as well as oral and maxillofacial abnormalities.
Stulberg et al. review hyperpigmentation. Café au lait spots may be congenital or develop during childhood and are a result of increased melanin production in melanocytes and basal keratinocytes. These spots typically appear on the trunk with a diameter of 0.2-4 cm in infants but may reach up to 30 cm in adults. Their borders may be either smooth or irregular.
Eichenfield et al. discuss the diagnostic criteria for neurofibromatosis, which requires two of the seven criteria for a diagnosis: 6 or more café au lait spots (size depends on age), 2 or more neurofibromas, 2 or more Lisch nodules, Crowe's sign, optic glioma, osseous lesions or thinning of the long bone cortex with or without pseudoarthritis, or a first-degree relative with neurofibromatosis.
Figure A shows a hyperpigmented macule known as a café-au-lait spot. Figure B shows numerous neurofibromas on the back of a patient with neurofibromatosis type I. Illustration A demonstrates Lisch nodules which are pigmented hamartomas of the iris. Illustration B shows the freckling in the axillary area known as Crowe's sign along with a café-au-lait spot.
Answer 1: VHL (von Hippel-Lindau), located on chromosome 3, is mutated in von Hippel-Lindau disease. von Hippel-Lindau disease presents with cavernous hemangiomas in the skin, mucosa, and viscera.
Answer 2: RB (retinoblastoma), located on chromosome 13, is mutated in retinoblastoma. Retinoblastoma is a malignancy of the retina presenting with vision loss, leukocoria, unilateral exophthalmos, and strabismus.
Answer 4: WT-1 (Wilms' tumor 1), located on chromosome 11, is mutated in Wilms' tumor. Wilms' tumor is an embryonal tumor of renal origin presenting with hematuria/dysuria, fever, and hypertension.
Answer 5: BRCA 1 (Breast cancer 1), located on chromosome 17, is mutated in many breast and ovarian cancers.
Stulberg DL, Clark N, Tovey D. Common hyperpigmentation disorders in adults: Part I. Diagnostic approach, café au lait macules, diffuse hyperpigmentation, sun exposure, and phototoxic reactions. Am Fam Physician. 2003 Nov 15;68(10):1955-60. Review.
PMID:14655804 (Link to Abstract)
Eichenfield LF, Levy ML, Paller AS, Riccardi VM. Guidelines of care for neurofibromatosis type 1. American Academy of Dermatology Guidelines/Outcomes Committee. J Am Acad Dermatol. 1997 Oct;37(4):625-30.
PMID:9344204 (Link to Abstract)