Cognitive-Behavioral Severity in Three Subtelomeric Microdeletion Disorders are Not Related to Deletion Size

Introduction: Chromosomal microdeletions are associated with various behavioral syndromes, intellectual disability (ID) and developmental delay (DD). The phenotype is usually identified first, possibly followed by the... [ view full abstract ]

Introduction: Chromosomal microdeletions are associated with various behavioral syndromes, intellectual disability (ID) and developmental delay (DD). The phenotype is usually identified first, possibly followed by the discovery of its molecular etiology.   Chromosomal microdeletions constitute a small proportion of copy-number variants (CNVs) on the human genome.  Microdeletions vary in size and involve one or more genes related to the phenotype.  Conventional wisdom in genetics is that disorder severity is associated with the deletion size.

Objective: The aim of this study was to examine the relationship between deletion size and phenotypic severity with respect to cognitive ability and adaptive behavior. 

Method: We recruited N=50 children ages 3-20 years, diagnosed with one of three subtelomeric microdeletions: 2q37, 8pinvdupdel, or 11q23-5. All participants were administered a battery of cognitive-behavioral tests including the Stanford-Binet 4^th Ed (SBFE) and Vineland Adaptive Behavior Scales (VABS) to assess intellectual ability (IQ) and adaptive behavior (DQ).  Of the 50 participants, blood was drawn or buccal smear employed to examine DNA and deletion size in N=17 subjects.  Deletion size, IQ and DQ were analyzed using SAS Ver. 9.4.

Results: Results show no significant correlation of deletion size with IQ (r=-0.17; p>0.51) or with DQ (r=-0.10; p>0.67).   Linear regression analysis also indicates no significant decrease in IQ as a function of deletion size (slope parameter  = -1.2; p>0.32), nor was there a significant decrease in DQ ( = -0.60; p>0.62.  Contrary to earlier investigations by researchers who occasionally find significant negative relationships between deletion size and cognitive-behavioral severity, we do not find this to be the case for the 3 subtelomeric deletions we examined, whether the subjects’ genetic disorders were analyzed jointly or severally.

Discussion: Results appear to be at variance to the concept of severity in genetic disorders.  The concept of severity in behavioral phenotypes will be reconsidered and redefined.