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Polymalformative genetic syndrome with increased risk of developing cancer
Polymalformative genetic syndrome with increased risk of developing cancer (PGSIRC) comprises a wide range of syndromes characterized by congenital malformations with a high risk of developing tumors including up to 50 different rare diseases.
ORPHA:183422Classification level: Group of disorders
- Synonym(s): -
- Prevalence: 1-5 / 10 000
- Inheritance: Autosomal dominant or Autosomal recessive
- Age of onset: All ages
- ICD-10: -
- OMIM: -
- UMLS: -
- MeSH: -
- GARD: -
- MedDRA: -
There are no published data on the prevalence of the set of all syndromes included in this category but, as each syndrome has its specific prevalence, it can be roughly estimated at 1/10,000.
PGSIRC encompasses different syndromes: the Overgrowth Syndromes, among which the Beckwith-Wiedemann syndrome with a 10% cumulative risk of cancer at 4 years of age mainly hepatoblastoma and Wilms' tumor, Costello syndrome with up to 10% risk of rhabdomyosarcoma, and other syndromes such as Simpson-Golabi-Behmel or Perlman (see these terms). Some other genetic rare diseases associated with an increased risk of cancer include tuberous sclerosis, Xeroderma pigmentosum or WAGR syndrome (see these terms). Because of this predisposition, it is essential to establish an early multidisciplinary follow-up protocol for each patient after the diagnosis. The clinical characteristics are specific to each syndrome.
The etiology is specific to each syndrome. The genetic alterations associated with tumorigenesis can occur in the germ-line, resulting in hereditary predisposition to cancer, or have their monoclonal origin in somatic cells, resulting in sporadic tumors. The exact mechanism by which alterations in cancer-related genes (i.e. RAS genes) produce both congenital polymalformative abnormalities as well as sporadic tumors is still under investigation.
The inheritance pattern is specific to each syndrome. In most cases of familial cancer, those not associated with congenital abnormalities, tumor susceptibility is inherited in an autosomal dominant pattern. In cancer associated to genetic rare diseases characterized by congenital malformations, the overall tumor susceptibility is inherited mainly in an autosomal recessive pattern, regardless of the inheritance pattern associated with the specific rare disease.
- Summary information
- Polski (2013, pdf)