APC-Related Phenotypes and Intellectual Disability in 5q Interstitial Deletions: A New Case and Review of the Literature

Abstract

The 5q deletion syndrome is a relatively rare condition caused by the monoallelic interstitial deletion of the long arm of chromosome 5. Patients described in literature usually present variable dysmorphic features, behavioral disturbance, and intellectual disability (ID); moreover, the involvement of the APC gene (5q22.2) in the deletion predisposes them to tumoral syndromes (Familial Adenomatous Polyposis and Gardner syndrome). Although the development of gastrointestinal tract malignancies has been extensively described, the genetic causes underlying neurologic manifestations have never been investigated. In this study, we described a new patient with a 19.85 Mb interstitial deletion identified by array-CGH and compared the deletions and the phenotypes reported in other patients already described in the literature and the Decipher database. Overlapping deletions allowed us to highlight a common region in 5q22.1q23.1, identifying KCNN2 (5q22.3) as the most likely candidate gene contributing to the neurologic phenotype.

Keywords: 5q deletion syndrome; KCNN2; array-CGH; intellectual disability.

Figure 1

Family pedigree. * A-CGH was performed on these subjects. ° MLPA, NGS, and clinical exome were performed for the index subject, II;4, indicated by a black arrow. Squares = males; circles = females; and black = family members affected. Genetic counseling was conducted for the whole family.

Figure 2

(A). Proband II;4: APC heterozygous deletion detected by MLPA (red dots at the 0.5 ratio value in the graph). (B). Heterozygous 5q21.3q23.2 deletion detected by a-CGH (CytoSure OGT Interpret Software, v.4.11).

Figure 3

Chromosome 5 ideogram and overlapping region in 5q deletions.