Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA
 

Naevoid basal cell carcinoma syndrome (NBCS)

Identity

Other namesGorlin 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 NamePTCH
    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

    OMIM109400
    OrphanetGorlin syndrome
    HGMD119447
    Other databaseNORD: Nevoid Basal Cell Carcinoma Syndrome
    AssociationBNCC Life Support Network

    Bibliography

    Complications of the naevoid basal cell carcinoma syndrome: results of a population based study.
    Evans DG, Ladusans EJ, Rimmer S, Burnell LD, Thakker N, Farndon PA
    Journal of medical genetics. 1993 ; 30 (6) : 460-464.
    PMID 8326488
     
    Syndromes of the head and neck.
    Gorlin RJ, Cohen MM, Levin LS
    Oxford Monogr Med Genet. 1990 ; 19 : 372-380.
     
    Compartment boundaries and the control of Drosophila limb pattern by hedgehog protein.
    Basler K, Struhl G
    Nature. 1994 ; 368 (6468) : 208-214.
    PMID 8145818
     
    The Drosophila segment polarity gene patched interacts with decapentaplegic in wing development.
    Capdevila J, Estrada MP, Sˆ°nchez-Herrero E, Guerrero I
    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
    Cell. 1996 ; 85 (6) : 841-851.
    PMID 8681379
     
    Human homolog of patched, a candidate gene for the basal cell nevus syndrome.
    Johnson RL, Rothman AL, Xie J, Goodrich LV, Bare JW, Bonifas JM, Quinn AG, Myers RM, Cox DR, Epstein EH Jr, Scott MP
    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 articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed

    Contributor(s)

    Written09-1997Jean-loup Huret

    Citation

    This paper should be referenced as such :
    Huret JL
    Naevoid basal cell carcinoma syndrome (NBCS);
    Atlas Genet Cytogenet Oncol Haematol. September 1997
    Free online version   Free pdf version   [Bibliographic record ]
    URL : http://AtlasGeneticsOncology.org/Kprones/NBC10005.html

    © Atlas of Genetics and Cytogenetics in Oncology and Haematology
    indexed on : Sat Jul 26 14:20:01 CEST 2014


    Home   Genes   Leukemias   Solid Tumours   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

    For comments and suggestions or contributions, please contact us

    jlhuret@AtlasGeneticsOncology.org.