The 7q11.23 Microduplication Syndrome: A Clinical Report with Review of Literature

Abstract

We report a 14-year-old adolescent girl with selective mutism (SM) and a 7q11.23 microduplication detected by chromosomal microarray (CMA) analysis and reviewed the literature from 18 published clinical reports. Our patient had specific phobias, SM, extreme anxiety, obesity, cutis marmorata, and a round appearing face with a short neck and over folded ears. We reviewed the published clinical, cognitive, behavioral, and cytogenetic findings grouped by speech and language delay, growth and development, craniofacial, clinical, and behavior and cognitive features due to the 7q11.23 microduplication. This microduplication syndrome is characterized by speech delay (91%), social anxiety (42%), attention deficit hyperactivity disorder (ADHD, 37%), autism spectrum disorder (29%), and separation anxiety (13%). Other findings include abnormal brain imaging (80%), congenital heart and vascular defects (54%), and mild intellectual disability (38%). We then compared the phenotype with Williams-Beuren syndrome (WBS) which is due to a deletion of the same chromosome region. Both syndromes have abnormal brain imaging, hypotonia, delayed motor development, joint laxity, mild intellectual disability, ADHD, autism, and poor visuospatial skills but opposite or dissimilar findings regarding speech and behavioral patterns, cardiovascular problems, and social interaction. Those with WBS are prone to have hyperverbal speech, lack of stranger anxiety, and supravalvular aortic stenosis while those with the 7q11.23 microduplication have speech delay, SM, social anxiety, and are prone to aortic dilatation.

Keywords: 7q11.23 microduplication; extreme anxiety; obesity; round appearing face; selective mutism; speech delay.

Fig. 1

A 1,478 Mb duplication (black rectangle) was found within the chromosome 7q11.23 band at genomic coordinates 72,664,088–74,142,215 with high resolution microarray analysis (NCBI build 37, Feb 2009, hg 19). The figure shows the duplication via both copy number pattern and single nucleotide probe allele peak patterns. The copy number probes indicating the presence of a duplication are noted above the baseline probes (representing a normal copy number of 2). The single nucleotide probes are present in two separate rows instead of a single row indicating the duplicated region. Genes fully included within this duplication were NSUN5, TRIM50, FKBP6, FZD9, BAZ1B, BCL7B, TBL2, MLXIPL, VPS37D, DNAJC30, WBSCR22, STX1A, MIR4284, ABHDD11-AS1, ABHD11, CLDN3, CLDN4, WBSCR27, WBSCR28, ELN, LIMK1, EIF4H, MIR590, LAT2, RFC2, CLIP2, and GTF2IRD1. Genes partially included within this duplication were GTF2IRD2P1 and GTF2I.