FaCD Online Syndrome Fact Sheet

Last updated: 20 Jul 2012

Name: Hereditary Desmoid Disease

Synonym: Familial Infiltrative Mesenteric Fibromatosis

Mode of Inheritance: AD

Genes

APC, mapped to 5q21-q22

Tumor features

colorectal adenomas
desmoid

Tumor features (possible)

adrenal adenoma
gastric leiomyoma
ovarian mucinous cystadenoma

Non-tumor features (possible)

neuropathy
seizures

Comment

This disorder is characterized by the occurrence of desmoids also known as mesenteric fibromatosis, and no polyps or only a few intestinal polyps (as opposed to classic familial adenomatous polyposis).Mutations have been found in specific regions of the APC gene[1-3].

Ozuner and Hull[4] reported 3 affected sisters with (multiple) intra-abdominal desmoids, diagnosed at the ages of 17, 22 and 25 years, in the absence of gastrointestinal polyps and a detectable mutation of the APC gene. Adrenal masses were detected in 2 of the sisters; histology could be obtained in 1: adrenal cortical adenoma. A mucinous ovarian cystadenoma was present in 1, and neurological symptoms in 2: one with seizures and another with a demyelinating peripheral neuropathy. No tumors could be detected on the pelvic/abdominal CT scan of the 2 brothers and both parents.

In a series of 44 pediatric desmoid patients, germline APC mutations were identified in 16% of the patients[7]. Desmoids can occur in sporadic cases in the absence of intestinal polyposis[5]. In these cases somatic beta-catenin mutations, encoded by CTNNB1, are commonly observed[6].
In a series of 11 pedriatic desmoid tumors with an abnormal nuclear ß-catenin accumulation, a somatic CTNNB1 mutation was detected in seven tumours. In two tumours with an abnormal nuclear ß-catenin accumulation and no CTNNB1 mutation, a germline APC mutation was identified[8]. One of the patients was already clinically known to have FAP, in the other case FAP was diagnosed in the father of the diagnosis desmoid in his child. The authors recommend to screen paediatric desmoid tumours for nuclear localisation of ß-catenin and consequently for CTNNB1 mutations. For patients with nuclear ß-catenin expression and no CTNNB1 mutations, APC mutation analysis should be offered[8].

References

[1] Caspari R, Olschwang S, Friedl W, Mandl M, Boisson C, Boker T, Augustin A, Kadmon M, Moslein G, Thomas G, Propping P. Familial adenomatous polyposis: Desmoid tumours and lack of ophthalmic lesions (CHRPE) associated with APC mutations beyond codon 1444. Hum Mol Genet 1995; 4:337-340.
[2] Eccles DM, Van der Luijt R, Breukel C, Bullman H, Bunyan D, Fisher A, Barber J, du Boulay C, Primrose J, Burn J, Fodde R. Hereditary desmoid disease due to a frameshift mutation at codon 1924 of the APC gene. Am J Hum Genet 59[6], 1193-1201. 1996.
[3] Scott RJ, Froggatt NJ, Trembath RC, Evans DGR, Hodgson SV, Maher ER. Familial infiltrative fibromatosis (desmoid tumours) (MIM135290) caused by a recurrent 3' APC gene mutation. Hum Mol Genet 5[12], 1921-1924. 1996.
[4] Ozuner G, Hull TL. Familial desmoids in association with adrenal and ovarian masses and leiomyomas: report of three cases. Dis Colon Rectum 1999; 42(4):529-532.
[5] Huerta S, Heubner DR, Marcus DR. Mesenteric fibromatosis in a young girl without familial adenomatous polyposis. Journal of pediatric surgery 2005; 40(5):e33-6.
[6] Kotiligam D, Lazar AJ, Pollock RE, Lev D. Desmoid tumor: a disease opportune for molecular insights. Histology and histopathology 2008; 23(1):117-26.
[7] Wang WL, Nero C, Pappo A, Dina Lev DL, Lazar AJ, Lopez-Terrada DH. CTNNB1 Genotyping and APC Screening in Pediatric Desmoid Tumors: A Proposed Alogrithm. Pediatr Dev Pathol. 2012 Feb 28. [Epub ahead of print]
[8] Kattentidt Mouravieva AA, Geurts-Giele IR, de Krijger RR, van Noesel MM, van de Ven CP, van den Ouweland AM, Kromosoeto JN, Dinjens WN, Dubbink HJ, Smits R, Wagner A. Identification of Familial Adenomatous Polyposis carriers among children with desmoid tumours. Eur J Cancer. Volume 48, Issue 12, August 2012; 1867–1874