A de novo deletion of chromosome 5q causing familial adenomatous polyposis, dysmorphic features, and mild mental retardation

Familial adenomatous polyposis (FAP) is an autosomal dominant disorder that typically presents with colorectal cancer secondary to extensive adenomato us polyps of the colon. The molecular basis and clinical phenotype of FAP a re well known. Recurrent episodes of severe abdominal pain and a positive f ecal occult blood test in an 18-yr-old boy with mild mental retardation and slight dysmorphic features of the face, head, and skeletal system led to t he diagnosis of FAR The clinical work-up revealed the presence of over 100 sessile colonic polyps but no polyp formation in the upper GI tract, no can cer development, nor other FAP-associated lesions. To find out whether ther e is an association between mental retardation and FAP we performed a chrom osome analysis including comparative genomic hybridization and an indirect genotype analysis with polymorphic markers from the APC gene region. Cytoge netic analysis showed an interstitial deletion of chromosomal region 5q tha t was confined to the region 5q2lq-22 by comparative genomic hybridization. The deletion, spanning about 10 centimorgans, encompassed the complete APC gene and can be considered as causative for FAP. Moreover, molecular genet ic analysis with polymorphic markers flanking the APC gene demonstrated a d e novo deletion on the paternal chromosome. Cytogenetically detectable dele tions on chromosome 5 including the APC gene generally lead to an associate d gene deletion syndrome. Individuals who present with mild mental retardat ion and dysmorphic features should therefore be investigated for chromosoma l deletions. If the deletion encompasses the APC gene, these patients are a t high risk of developing FAP and associated complications. (Am J Gastroent erol 2001;96:3016-3020. (C) 2001 by Am. Coll. of Gastroenterology).