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 adenomatous polyps of the colon. The molecular basis and clinical phenotype of FAP are well known. Recurrent episodes of severe abdominal pain and a positive fecal 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 the diagnosis of FAP. The clinical workup revealed the presence of over 100 sessile colonic polyps but no polyp formation in the upper GI tract, no cancer development, nor other FAP-associated lesions. To find out whether there is an association between mental retardation and FAP we performed a chromosome analysis including comparative genomic hybridization and an indirect genotype analysis with polymorphic markers from the APC gene region. Cytogenetic analysis showed an interstitial deletion of chromosomal region 5q that was confined to the region 5q21-q22 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 genetic analysis with polymorphic markers flanking the APC gene demonstrated a de novo deletion on the paternal chromosome. Cytogenetically detectable deletions on chromosome 5 including the APC gene generally lead to an associated gene deletion syndrome. Individuals who present with mild mental retardation and dysmorphic features should therefore be investigated for chromosomal deletions. If the deletion encompasses the APC gene, these patients are at high risk of developing FAP and associated complications.