Faculty Bibliography

Albinism connotes a large group of genetic disorders that are characterized by diminished ocular and oftentimes cutaneous pigmentation. These disorders are generally subclassified as oculocutaneous albinism (OCA) or ocular albinism (OA) based on the extent of their effects on the pigmentation of the skin and hair. Sometimes, different mutations in the same gene can cause OCA or OA

BACKGROUND: Patients with large congenital melanocytic nevi (LCMN) are at greater risk for the development of malignant melanoma (MM) than are persons in the general population. OBJECTIVE: Our purpose was to identify the clinical features of LCMN in those patients in whom MMs actually developed. METHODS: The records of 117 patients in the New York University Registry of LCMN and the reports of 172 cases of LCMN in the world literature were studied. RESULTS: Of the 289 cases of LCMN studied, 34 patients (12%) had primary cutaneous MMs within their nevi; in two additional patients, MMs developed at cutaneous sites other than within their nevi. All patients in whom MM developed within LCMN had nevi in axial locations; however, 91% of the LCMN were axial. No MM was found that had arisen in any of the 26 LCMN confined to the extremities. In addition, no MM was found that had arisen in thousands of satellite nevi. CONCLUSION: When MM develops within an LCMN, it generally does so in those LCMN in an axial location. The absence of cases of MM arising in LCMN confined to the extremities suggests that such nevi represent lower risk lesions, but the number of extremity nevi analyzed was too small to allow definitive conclusions. A striking finding was the absence of MMs arising in satellite nevi

The purpose of this study was to investigate factors regulating melanogenesis in cultured human uveal melanocytes. The effects of various substances on the melanin content, tyrosinase activity and growth of cultured uveal melanocytes were tested. 12-O-tetradecanoyl-phorbol-13-acetate (a protein kinase C activator) and various cAMP-elevating agents, including isobutylmethylxanthine, cholera, toxin, and dibutyryl-cAMP increased melanin content per culture, tyrosinase activity and cell numbers of uveal melanocytes in a dose dependent manner. Basic fibroblast growth factor (tyrosine kinase activator) stimulated growth but did not affect melanin content per culture of uveal melanocytes in vitro. These results indicate that cAMP-elevating agents and protein kinase C activator stimulate melanogenesis and growth of cultured uveal melanocytes. Tyrosine kinase activator stimulates growth but not melanogenesis of cultured uveal melanocytes

Ocular albinism type 1 (OA1) is an X-linked human genetic disorder that affects retinal pigment cells and, to a lesser degree, neural crest-derived melanocytes. The OA1 gene is located close to the pseudoautosomal region and predicts a novel protein whose function is unknown. However, histologic studies of affected patients have suggested a potential role in melanosome biogenesis. Here we report the isolation and characterization of the mouse homolog of the human OA1 gene, termed Moa1. Two Moa1 isoforms were isolated from a melanoma cDNA library and predicted to encode proteins of 405 and 249 amino acids with six and two transmembrane-spanning regions, respectively. Interspecific backcross mapping yielded a map order and distances (cM) of cen-Moa1-3.1 +/- 1.8-Piga-2.1 +/- 1.5-Amel, indicating that Moa1 is located much farther away from the pseudoautosomal region than its human homolog. In adult tissues, both Moa1 isoforms were detected in the eye by Northern hybridization. In neonatal tissues, Moa1 RNA was detected in both skin and eyes by Northern hybridization and was not affected by the absence of pigment in mice carrying the albino mutation, or by the type of pigment synthesized, i.e., eumelanin vs pheomelanin, in mice carrying the black-and-tan mutation. Expression of Moa1 RNA was not detected in embryonic tissues by Northern analysis or by in situ hybridization despite the active synthesis of ocular pigment by E16.5. These results provide insight into the structure and possible function of the OA1 protein and suggest a more complex relationship between the human and mouse X chromosomes than was previously thought to exist

BACKGROUND: Patients with a large congenital melanocytic nevus (LCMN) may have associated leptomeningeal melanocytosis with or without central nervous system (CNS) melanomas. These patients are considered to have neurocutaneous melanosis, a disorder that, when symptomatic or otherwise manifest neurologically, carries a poor prognosis even in the absence of malignancy. OBJECTIVE: Our purpose was to identify typical clinical features in patients who have manifest CNS melanosis in association with LCMN. METHODS: The records of 117 patients with LCMN in the New York University Registry of LCMN and the reports of 172 cases of LCMN in the world literature were included for features that might signal a high risk for the development of manifest CNS involvement. RESULTS: Of the 289 patients with LCMN, 33 had manifest CNS melanosis. In all 33 in whom symptomatic neurocutaneous melanosis was diagnosed, the LCMNs were present in a posterior axial location on the head, neck, back, and/or buttocks. 'Satellite' nevi were known to be present in 31 of the 33 patients. CONCLUSION: Patients with LCMN in a posterior axial location, especially when associated with 'satellite' melanocytic nevi, are at greater risk for the development of manifest neurocutaneous melanosis than patients with LCMN limited to the extremities or those who are lacking satellite nevi

OBJECTIVE: To define the spectrum of disease in cases of hypopigmentation and hyperpigmentation along the lines of Blaschko more accurately. Pigmentary anomalies along the lines of Blaschko, including hypomelanosis of Ito, linear and whorled nevoid hypermelanosis, and nevus depigmentosus, can be associated with notable abnormal systemic features. We believe that the incidence of associated abnormal features described in previous studies is exaggerated owing to referral and reporting bias. DESIGN: Retrospective review of case series. SETTING: An ambulatory, university hospital, pediatric dermatology practice and a large, city hospital, pediatric dermatology clinic. PATIENTS: Fifty-four children referred consecutively over a 5-year period for evaluation of segmental, linear, or swirled hypopigmentation and/or hyperpigmentation along the lines of Blaschko. MAIN OUTCOME MEASURE: Incidence of associated abnormal systemic features. RESULTS: Extracutaneous abnormal features were present in 16 (30%) of 54 children with aberrant pigmentation along the lines of Blaschko: in 9 (33%) of 27 with hypomelanosis of Ito, in 4 (31%) of 13 with linear and whorled nevoid hypermelanosis, in 1 (11%) of 9 with nevus depigmentosus, and in 2 (40%) of 5 with coexistent hypopigmentation and hyperpigmentation. CONCLUSIONS: Pigmentary anomalies along the lines of Blaschko are associated with abnormal systemic features far less often than has been reported previously. These pigmentary anomalies should not be considered distinct syndromes but rather grouped as a heterogeneous collection of disorders indicative of underlying genetic mosaicism. Such a classification will allow better understanding and evaluation of affected persons

BACKGROUND: The term Bannayan-Riley-Ruvalcaba syndrome has been proposed to reflect the clinical overlap of 3 conditions previously described as separate entities, each inherited in an autosomal dominant fashion. They are the Riley-Smith, Bannayan-Zonana, and Ruvalcaba-Myhre-Smith syndromes. OBSERVATIONS: We studied 2 kindreds with the Bannayan-Riley-Ruvalcaba syndrome. Characteristic cutaneous findings included multiple subcutaneous lipomas and vascular malformations, lentigines of the penis and vulva, verrucae, and acanthosis nigricans. Macrocephaly with normal ventricular size, mental retardation, central nervous system vascular malformations, intestinal polyposis, skeletal abnormalities, and thyroid tumors were the most common systemic featues. A striking clinical finding in 1 patient was widespread verrucous changes of both lips that histologically showed epidermal hyperplasia with papillomatosis and hyperkeratosis. Biopsy specimens of facial papules demonstrated the histological features of both syringomas and trichilemmomas. Lentiginous hyperplasia of the epidermis with increased pigment in the basal layer and a slight increase in the number of melanocytes were seen in biopsy specimens of the penile lentigines. CONCLUSIONS: The histologic findings of both the facial lesions and the pigmented macules of the penis in the Bannayan-Riley-Ruvalcaba syndrome have not, to our knowledge, been reported previously. The similarities between the Bannayan-Riley-Ruvalcaba syndrome and Cowden disease raise the possibility of a common genetic pathogenesis for these 2 diseases