Differences in neuropsychological and behavioral parameters and brain structure in patients with familial adenomatous polyposis: a sibling-paired study.

Amie Blanco,Megan Myers,Peggy Conrad,James Barkovich,Jonathan P. Terdiman,Rita J. Jeremy,Trilokesh D. Kidambi,Ana Sánchez Azofra

doi:10.1186/s13053-016-0060-7

Abstract

BackgroundFamilial adenomatous polyposis (FAP) is an autosomal dominant hereditary colon cancer syndrome caused by mutations in adenomatous polyposis coli (APC) with both colonic and extra-colonic manifestations. Case reports have noted an association with FAP and intellectual disability and animal studies have shown that APC is implicated in neural development and function, but no studies have investigated neuropsychological, behavioral, or structural brain characteristics of patients with FAP.MethodsWe undertook a pilot, sibling-pair study comparing three patients with FAP to their sex-matched siblings without FAP. Each sibling pair underwent neuropsychological testing by a blinded examiner, high resolution brain MRI scans, and the mother of each pair rated her children’s adaptive life skills and behavioral and emotional characteristics. Given the small number of study participants in this pilot study, quantitative comparisons of results were made by subtracting the score of the non-FAP sibling from the FAP patient on the various neuropsychological tests and parent rating questionnaires to calculate a difference, which was then divided by the standard deviation for each individual test to determine the difference, corrected for the standard deviation. Diffusion numbers in multiple regions of the brain as assessed by MRI were calculated for each study participant.ResultsWe found similarity between siblings in all three pairs on a wide range of neuropsychological measures (general intelligence, executive function, and basic academic skills) as tested by the psychologist as well as in descriptions of adaptive life skills as rated by mothers. However, mothers’ ratings of behavioral and emotional characteristics of two of the three pairs showed differences between the siblings, specifically that the patients with FAP were found to have more behavioral and emotional problems compared to their siblings. No differences in brain structure were identified by MRI.ConclusionWe report the first study exploring neuropsychological, behavioral, emotional, and structural brain characteristics of patients with FAP and found subjective differences as assessed by maternal perception in behavioral and emotional characteristics in patients with FAP compared to their siblings. Larger studies are needed to elucidate the relationship, if any, between FAP and brain function.

Highlights

Familial adenomatous polyposis (FAP) is an autosomal dominant hereditary colon cancer syndrome caused by mutations in adenomatous polyposis coli (APC) with both colonic and extra-colonic manifestations
Familial adenomatous polyposis (FAP) is an autosomal dominant hereditary colon cancer syndrome characterized by 100 or more premalignant polyps caused by germline mutations in the tumor suppressor gene, adenomatous polyposis coli (APC), located on chromosome 5q21-q22 [1, 2]
Clinical and genetic profiles Family 1 The proband was a 20-year-old Caucasian woman who underwent genetic testing at the age of seven due to a family history of FAP and tested positive for the known family APC Q1045X mutation. Her first colonoscopy was performed at the age of ten and multiple sessile adenomas were found throughout the colon

Summary

Introduction

Familial adenomatous polyposis (FAP) is an autosomal dominant hereditary colon cancer syndrome caused by mutations in adenomatous polyposis coli (APC) with both colonic and extra-colonic manifestations. Familial adenomatous polyposis (FAP) is an autosomal dominant hereditary colon cancer syndrome characterized by 100 or more premalignant polyps caused by germline mutations in the tumor suppressor gene, adenomatous polyposis coli (APC), located on chromosome 5q21-q22 [1, 2]. Case reports have linked FAP to the presence of intellectual disability (formerly called mental retardation) [1, 4,5,6,7,8,9,10] In each of these cases, the individuals had a deletion of all or a portion of chromosome 5q, but the nature of the intellectual disability was poorly defined and it remained unclear whether the intellectual disability was secondary to loss of APC gene function or another genetic defect due to the chromosomal loss. Studies in mice with a mutated APC gene have shown learning and memory impairments, autisticlike behaviors, increased repetitive behaviors, reduced social interest, increased locomotor activity as well as abnormal brain morphology and function [16, 17]

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