title: A Rare Recurrent 4q25 Proximal Deletion Not Involving the PITX2 Gene: A Genomic Disorder Distinct from Axenfeld-Rieger Syndrome.
abstract: Haploinsufficient microdeletions within chromosome 4q25 are often associated with Axenfeld-Rieger syndrome. A de novo 4q25 deletion, 675 kb proximal to PITX2, has previously been reported once in an adult patient. The patient did not have Axenfeld-Rieger anomaly, but instead had intellectual disability and a complex behavioral phenotype with withdrawn, stereotypic, and ritualistic behavior. Array comparative genome hybridization demonstrated a smaller, overlapping 4q25 deletion in a 2-year-old patient and his mother, both having significant phenotypic overlap with the initially reported patient. All 3 patients have distinct facial features (including mild hypotelorism and subtle mandibular asymmetry), developmental delay, and complex behavioral difficulties. A genotype-phenotype correlation narrows the shared phenotype to a common COL25A1 gene aberration and proposes that the concurrent EGF gene loss has a significant impact on the phenotypic severity. Overall, our patients provide data to support the existence of a novel 4q25 proximal deletion syndrome.
authors: Department of Pediatrics, Developmental Pediatrics Division, Saint Louis University School of Medicine, St. Louis, Mo., USA.
authors: Jennifer L
authors: JL
authors: Heithaus
authors: Department of Pediatrics, Developmental Pediatrics Division, Saint Louis University School of Medicine, St. Louis, Mo., USA.
authors: Kimberly A
authors: KA
authors: Twyman
authors: Department of Pediatrics, Genetics Division, Saint Louis University School of Medicine, St. Louis, Mo., USA; Department of Pediatrics, Molecular Cytogenetics Laboratory, SSM Cardinal Glennon Children's Hospital, St. Louis, Mo., USA.
authors: Jacqueline R
authors: JR
authors: Batanian
keywords: COL25A1; Developmental delay; EGF; Hypotelorism; Hypotonia; Mandible asymmetry; Microdeletion 4q25