Naevoid basal cell carcinoma syndrome (NBCS)

Other names	- Gorlin syndrome
	- Gorlin-Goltz syndrome
	- Multiple basal cell nevi, odontogenic keratocysts, skeletal anomalies
	- Fifth phacomatosis
	- Hydrocephalus, costovertebral dysplasia, sprengel anomaly
Inheritance	autosomal dominant with complete penetrance, but variable expressivity; 40% are de novo mutations; frequency is about 2/105 newborns

Clinics

Note	NBCS is an hamartoneoplastic syndrome; it is also a chromosome instability syndrome; hamartomas are localized tissue proliferations with faulty differenciation and mixture of component tissues; they are heritable malformations that have a potential towards neoplasia
Phenotype and clinics	multiple basal cell carcinomas, appearing as early as 15 yrs jaw keratocysts dyskeratotic palmar/plantar pits skeletal malformations (of ribs, spina bifida occulta, ...) soft tissue calcifications (falx cerebri, ovarian fibroma, diaphragma sellae, ...) facial dysmorphia
Neoplastic risk	mainly multiple basal cell carcinomas; other proliferations (see below) in 60% of patients other malignancies: medulloblastoma, ovarian fibrosarcoma benign proliferations: ovarian fibroma, meningioma, rhabdomyoma, cardiac fibroma.
Treatment	tumour exereses
Evolution	extensive number of basal cell carcinomas
Prognosis	according to the tumours (basal cell carcinomas are not life threatening, but may be devastating)

Cytogenetics

Inborn conditions	- spontaneous and induced chromosome instability - delay in the cell cycle - NBCS is therefore a chromosome instability syndrome
Cytogenetics of cancer	poorly documented

Genes involved and Proteins

Complementation groups

none so far

 

Gene Name	PTCH
Location	in 9q22.3 (between FACC and XPAC !!)

Protein
Description	glycoprotein with transmembrane domains, extra cellular loops, and intracellular domains
Localisation	transmembrane protein
Function	part of a signalling pathway; probable cell to cell adhesion role; may have a repressive activity on cell proliferation; as NBCS syndrome is a chromosome instability syndrome, this protein may have a role in DNA maintenance, repair and/or replication

Mutations
Germinal	most germ-line mutations in NBCS patients lead to protein truncation, which suggests that developmental anomalies seen in NBCS may be due to haplo-insufficiency; no obvious genotype-phenotype correlations
Somatic	mutation and allele loss events in basal cell carcinoma, in NBCS and in sporadic basal cell carcinoma are, so far, in accordance with the two-hit model for neoplasia, as is found in retinoblastoma.

External links

GeneCards	NBCCS
OMIM	109400
Orphanet	Gorlin syndrome
HGMD	119447
Other database	NORD: Nevoid Basal Cell Carcinoma Syndrome
Association	BNCC Life Support Network

Bibliography

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PMID 8326488

Syndromes of the head and neck.

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The Drosophila segment polarity gene patched interacts with decapentaplegic in wing development.

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The EMBO journal. 1994 ; 13 (1) : 71-82.

PMID 8306973

The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas.

Gailani MR, Stˆ€hle-Bˆ§ckdahl M, Leffell DJ, Glynn M, Zaphiropoulos PG, Pressman C, Undˆ©n AB, Dean M, Brash DE, Bale AE, Toftgˆ€rd R

Nature genetics. 1996 ; 14 (1) : 78-81.

PMID 8782823

A mammalian patched homolog is expressed in target tissues of sonic hedgehog and maps to a region associated with developmental abnormalities.

Hahn H, Christiansen J, Wicking C, Zaphiropoulos PG, Chidambaram A, Gerrard B, Vorechovsky I, Bale AE, Toftgard R, Dean M, Wainwright B

The Journal of biological chemistry. 1996 ; 271 (21) : 12125-12128.

PMID 8647801

Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome.

Hahn H, Wicking C, Zaphiropoulous PG, Gailani MR, Shanley S, Chidambaram A, Vorechovsky I, Holmberg E, Unden AB, Gillies S, Negus K, Smyth I, Pressman C, Leffell DJ, Gerrard B, Goldstein AM, Dean M, Toftgard R, Chenevix-Trench G, Wainwright B, Bale AE

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PMID 8681379

Human homolog of patched, a candidate gene for the basal cell nevus syndrome.

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Science (New York, N.Y.). 1996 ; 272 (5268) : 1668-1671.

PMID 8658145

The naevoid basal-cell carcinoma syndrome (Gorlin syndrome) is a chromosomal instability syndrome.

Shafei-Benaissa E, Savage JR, Babin P, Larrˆ®gue M, Papworth D, Tanzer J, Bonnetblanc JM, Huret JL

Mutation research. 1998 ; 397 (2) : 287-292.

PMID 9541654

The Drosophila hedgehog gene is expressed specifically in posterior compartment cells and is a target of engrailed regulation.

Tabata T, Eaton S, Kornberg TB

Genes & development. 1992 ; 6 (12B) : 2635-2645.

PMID 1340474

Most germ-line mutations in the nevoid basal cell carcinoma syndrome lead to a premature termination of the PATCHED protein, and no genotype-phenotype correlations are evident.

Wicking C, Shanley S, Smyth I, Gillies S, Negus K, Graham S, Suthers G, Haites N, Edwards M, Wainwright B, Chenevix-Trench G

American journal of human genetics. 1997 ; 60 (1) : 21-26.

PMID 8981943

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed

Contributor(s)

Written	09-1997	Jean-loup Huret

Citation

This paper should be referenced as such :

Huret JL . Naevoid basal cell carcinoma syndrome (NBCS). Atlas Genet Cytogenet Oncol Haematol. Septem ber 1997 . URL : http://AtlasGeneticsOncology.org/Genes/NBC10005.html

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indexed on : Mon Aug 11 21:21:41 2008

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