Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome.

Nevoid basal cell carcinoma syndrome (NBCC; Gorlin syndrome), an autosomal dominant disorder linked to 9q22.3-q31, and caused by mutations in PTC, the human homologue of the Drosophila patched gene, comprises multiple basal cell carcinomas, keratocysts of the jaw, palmar/plantar pits, spine and rib anomalies and calcification of the falx cerebri. We reviewed the findings on 105 affected individuals examined at the NIH 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 (median 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 (median 3). Palmar pits and plantar pits were seen in 87%. Ovarian fibromas were diagnosed by ultrasound in 9/52 (17%) at a mean age of 30 years. Medulloblastoma occurred in 4 patients at a mean age of 2.3 years. Three patients had cleft lip or palate. Physical findings include "coarse face" in 54%, relative macrocephaly in 50%, hypertelorism in 42%, frontal bossing in 27%, pectus deformity in 13%, and Sprengel deformity in 11%. Important radiological signs included calcification of the falx cerebri in 65%, of the tentorium cerebelli in 20%, bridged sella in 68%, bifid ribs in 26%, hemivertebrae in 15%, fusion of the vertebral bodies in 10%, and flame shaped lucencies of the phalanges, metacarpal, and carpal bones of the hands in 30%. Several traits previously considered components of the syndrome (including short fourth metacarpal, 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 in NBCC in a large population of US patients and discusses guidelines for diagnosis and management.

[1]  A. Goldstein,et al.  Nevoid basal cell carcinoma syndrome with medulloblastoma in an African-American boy: a rare case illustrating gene-environment interaction. , 1997, American journal of medical genetics.

[2]  Michael Dean,et al.  Mutations of the Human Homolog of Drosophila patched in the Nevoid Basal Cell Carcinoma Syndrome , 1996, Cell.

[3]  R. Myers,et al.  Human Homolog of patched, a Candidate Gene for the Basal Cell Nevus Syndrome , 1996, Science.

[4]  A. Goldstein,et al.  Fine mapping of the locus for nevoid basal cell carcinoma syndrome on chromosome 9q. , 1994, The Journal of investigative dermatology.

[5]  G. Chenevix-Trench,et al.  Fine genetic mapping of the gene for nevoid basal cell carcinoma syndrome. , 1994, Genomics.

[6]  A. Goldstein,et al.  Localization of the gene for the nevoid basal cell carcinoma syndrome. , 1994, American journal of human genetics.

[7]  E. Haan,et al.  Nevoid basal cell carcinoma syndrome: review of 118 affected individuals. , 1994, American journal of medical genetics.

[8]  A. Goldstein,et al.  Clinical findings in two African-American families with the nevoid basal cell carcinoma syndrome (NBCC). , 1994, American journal of medical genetics.

[9]  E. Haan,et al.  Further localization of the gene for nevoid basal cell carcinoma syndrome (NBCCS) in 15 Australasian families: linkage and loss of heterozygosity. , 1993, American journal of human genetics.

[10]  A. Goldstein,et al.  Sun exposure and basal cell carcinomas in the nevoid basal cell carcinoma syndrome. , 1993, Journal of the American Academy of Dermatology.

[11]  C. Wilson,et al.  Meningiomas induced by high-dose cranial irradiation. , 1993, Journal of neurosurgery.

[12]  D. Evans,et al.  Complications of the naevoid basal cell carcinoma syndrome: results of a population based study. , 1993, Journal of medical genetics.

[13]  R. Richards,et al.  Anticipation legitimized: unstable DNA to the rescue. , 1992, American journal of human genetics.

[14]  M. Greene,et al.  Developmental defects in gorlin syndrome related to a putative tumor suppressor gene on chromosome 9 , 1992, Cell.

[15]  D. Evans,et al.  Location of gene for Gorlin syndrome , 1992, The Lancet.

[16]  R. Wegner,et al.  Localisation of gene for the naevoid basal-cell carcinoma syndrome , 1992, The Lancet.

[17]  C. Coffin.  Congenital cardiac fibroma associated with Gorlin syndrome. , 1992, Pediatric pathology.

[18]  D. Evans,et al.  The incidence of Gorlin syndrome in 173 consecutive cases of medulloblastoma. , 1991, British Journal of Cancer.

[19]  C. Amos,et al.  Relationship between head circumference and height in normal adults and in the nevoid basal cell carcinoma syndrome and neurofibromatosis type I. , 1991, American journal of medical genetics.

[20]  J. Hall,et al.  Genomic imprinting: review and relevance to human diseases. , 1990, American journal of human genetics.

[21]  M. Berger,et al.  Radiation-induced meningiomas in pediatric patients. , 1988, Neurosurgery.

[22]  K. Benirschke,et al.  The Gorlin syndrome: a genetically determined disorder associated with cardiac tumor. , 1987, American heart journal.

[23]  Robert J. Gorlin,et al.  Nevoid Basal‐Cell Carcinoma Syndrome , 1987, Medicine.

[24]  K. Jones,et al.  The Gorlin syndrome: a genetically determined disorder associated with cardiac tumor. , 1986, The Journal of thoracic and cardiovascular surgery.

[25]  C. Treip,et al.  Radiation‐induced intracranial neoplasms. A report of three possible cases , 1984, Cancer.

[26]  A. Chaudhry,et al.  Multiple nevoid basal cell carcinoma syndrome. , 1982, Journal of oral medicine.

[27]  M. Apuzzo,et al.  Multiple meningiomas following radiation therapy for medulloblastoma. Case report. , 1981, Journal of neurosurgery.

[28]  Dunnick Nr,et al.  Nevoid Basal Cell Carcinoma Syndrome: Radiographic Manifestations Including Cystlike Lesions of the Phalanges , 1978 .

[29]  L. Strong.  Genetic and environmental interactions , 1977, Cancer.

[30]  Gorlin Rj,et al.  The multiple nevoid basal cell carcinoma syndrome revisited. , 1971 .

[31]  J. Howell,et al.  Pursuit of the pits in the nevoid basal cell carcinoma syndrome. , 1970, Archives of dermatology.

[32]  R. Bloom.  The metacarpal sign. , 1970, The British journal of radiology.

[33]  Tamoney Hj.  Basal cell nevoid syndrome. , 1969 .

[34]  R. Gorlin,et al.  The multiple basal‐cell nevi syndrome. An analysis of a syndrome consisting of multiple nevoid basal‐cell carcinoma, jaw cysts, skeletal anomalies, medulloblastoma, and hyporesponsiveness to parathormone , 1965 .

[35]  J. Block,et al.  OVARIAN FIBROMAS AND MESENTERIC CYSTS: THEIR ASSOCIATION WITH HEREDITARY BASAL CELL CANCER OF THE SKIN. , 1963, American journal of obstetrics and gynecology.

[36]  R. Gorlin,et al.  Multiple nevoid basal-cell epithelioma, jaw cysts and bifid rib. A syndrome. , 1960, The New England journal of medicine.

[37]  S. Pollack,et al.  Basal cell carcinoma in young patients after irradiation for childhood malignancy. , 1991, Medical and pediatric oncology.

[38]  F. Domínguez,et al.  Comparative study of keratocysts, associated and non-associated with nevoid basal cell carcinoma syndrome. , 1988, Journal of oral pathology.

[39]  B. Littler.  Gorlin's syndrome and the heart. , 1979, The British journal of oral surgery.

[40]  W. Bossert,et al.  Normal values for selected physical parameters: an aid to syndrome delineation. , 1974, Birth defects original article series.

[41]  B. McEvoy,et al.  Multiple nevoid basal cell carcinoma syndrome:radiological manifestations. , 1969, The British journal of radiology.

[42]  D. Anderson,et al.  The nevoid basal cell carcinoma syndrome. , 1967, American journal of human genetics.

[43]  A. Wiskemann,et al.  [The fifth phakomatosis. Basal cell nevus with hereditary malformation and medulloblastoma]. , 1963, Dermatologica.

[44]  R. Gorlin,et al.  Multiple nevoid basal cell carcinoma, odontogenic keratocysts and skeletal anomalies. A syndrome. , 1963, Acta dermato-venereologica.

[45]  J. Howell,et al.  The basal-cell nevus: its relationship to multiple cutaneous cancers and associated anomalies of development. , 1959, A.M.A. archives of dermatology.

[46]  G. Binkley,et al.  Epithelioma adenoides cysticum; basal cell nevi, agenesis of the corpus callosum and dental cysts; a clinical and autopsy study. , 1951, A.M.A. archives of dermatology and syphilology.