An unusually severe phenotype for familial adenomatous polyposis
a Wessex Clinical Genetics Service, Southampton, b Clinical Genetics
Service, Institute of Child Health, Royal Hospital for Sick Children,
Bristol, c DNA Laboratory, West
Midlands Regional Genetics Service, Birmingham Heartlands
Hospital, d Child Health, Southampton General Hospital, e Institute of Child Health, Royal Hospital
for Sick Children, Bristol
Correspondence to: Dr Diana M Eccles, Wessex Clinical Genetics Service, Princess Ann Hospital, Coxford Road, Southampton SO16 6YA.
Accepted 8 July 1997
Familial adenomatous polyposis (FAP) is a dominantly inherited
predisposition to the development of many hundreds to thousands of
adenomatous polyps of the colon. The mean age of onset is around 15 years, symptoms may arise in the third decade, and the median age for
the development of colonic cancer is 35-40 years. Prophylactic colectomy reduces the risk of death from colorectal cancer to such an
extent that late sequelae such as upper gastrointestinal tumours have
become the main cause of mortality in appropriately managed
patients. The age at which colonic surveillance begins reflects the
natural history of the disease. Onset of polyp formation and cancer in
childhood is very unusual, but has recently been associated with a
specific mutation at codon 1309 in exon 15 where a more severe
phenotype is sometimes observed. The case histories of two families
are reported in which there is childhood onset of polyps in the
youngest generation and in one case a carcinoma, in whom mutations have
been identified in exon 11 of the APC gene. Several other affected
relatives were diagnosed at ages ranging from 5-48 years, some already
with a cancer at the time of first screening. Since the aim of
screening for colonic polyps is prevention of colonic cancer, family
members at risk should be offered genetic assessment and direct
mutation testing where this is possible, usually in the early teens. In
the absence of a genetic test (the situation in about one third of
families) or in a known gene carrier, annual colonoscopy
examination is advised from the same age. Clinicians should take note
of the family history and be prepared to consider much earlier
intervention if symptoms occur in a child with a family history of FAP.
Where childhood onset of polyps has occurred, other children at risk in
the family must be offered earlier genetic testing and endoscopic surveillance.
© 1997 by Archives of Disease in Childhood
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