CLINICAL MANIFESTATIONS IN 105 PERSONS WITH NEVOID BASAL-CELL CARCINOMA SYNDROME

Nevoid basal cell carcinoma syndrome (NBCC; Gorlin syndrome), an autos omal dominant disorder linked to 9q22.3-q31, and caused by mutations i n PTC, the human homologue of the Drosophila patched gene, comprises m ultiple basal cell carcinomas, keratocysts of the jaw, palmar/plantar pits, spine and rib anomalies and calcification of the fair cerebri. W e reviewed the findings on 105 affected individuals examined at the NI H since 1985. The data included 48 males and 57 females ranging in age from 4 months to 87 years. Eighty percent of whites (71/90) and 38% ( 5/13) of African-Americans had at least one basal cell carcinoma (BCC) , with the first tumor occurring at a mean age of 23 (median 20) years and 21 (median 20) years, respectively. Excluding individuals exposed to radiation therapy, the number of BCCs ranged from 1 to >1,000 (med ian 8) and 1 to 3 (median 2), respectively, in the 2 groups. Jaw cysts occurred in 78/105 (74%) with the first tumor occurring in 80% by the age of 20 years. The number of total jaw cysts ranged from 1 to 28 (m edian 3). Palmar pits and plantar pits were seen in 87%. Ovarian fibro mas were diagnosed by ultrasound in 9/52 (17%) at a mean age of 30 yea rs. Medulloblastoma occurred in 4 patients at a mean age of 2.3 years. Three patients had cleft lip or palate. Physical findings include ''c oarse face'' in 54%, relative macrocephaly in 50%, hypertelorism in 42 %, frontal bossing in 27%, pectus deformity in 13%, and Sprengel defor mity in 11%. Important radiological signs included calcification of th e fair cerebri in 65%, of the tentorium cerebelli in 20%, bridged sell a in 68%, bifid ribs in 26%, hemivertebrae in 15%, fusion of the verte bral bodies in 10%, and flame shaped lucencies of the phalanges, metac arpal, and carpal bones of the hands in 30%. Several traits previously considered components of the syndrome (including short fourth metacar pal, scoliosis, cervical ribs and spina bifida occulta) were not found to be significantly increased in the affected individuals. This study delineates the frequency of the clinical and radiological anomalies i n NBCC in a large population of US patients and discusses guidelines f or diagnosis and management. (C) 1997 Wiley-Liss, Inc.