Familial adenomatous polyposis in a patient with unexplained mental retardation

Background: A 22-year-old woman was referred to a genomic medicine clinic for evaluation of suspected Prader-Willi syndrome (PWS) after normal DNA methylation studies on chromosome 15 were obtained. Features suggestive of PWS included mental retardation, short stature, obesity, hypotonia, and small hands and feet. The patient, however, lacked many PWS-defining behavioral features, including hyperphagia, compulsive skin picking, and food-seeking behaviors. Investigations: DNA methylation studies on chromosome 15 were completed before the patient's presentation. At the genomic medicine clinic, she underwent standard karyotyping, array comparative genomic hybridization, fluorescent in situ hybridization analysis, colonoscopy, endoscopy, thyroid ultrasound, and thyroid fine needle aspiration biopsy. Diagnosis: Familial adenomatous polyposis with mental retardation, caused by an interstitial deletion of the long arm of chromosome 5 encompassing the APC (adenomatous polyposis coli) tumor suppressor locus. Management: Colectomy with ileorectal anastomosis and thyroidectomy with subsequent iodine-131 therapy. The patient also underwent genetic counseling and was prescribed a program of caloric reduction and exercise.