Bilateral Radial Ulnar Synostosis and Vertebral Anomalies in a Child with a De Novo 16p13.3 Interstitial Deletion

We describe an 8-year-old boy with developmental delay, clinical bilateral radial ulnar synostosis, Klippel-Feil anomaly, and other vertebral deformities who was found to have a de novo deletion of 114.5kb at 16p13.3. The deletion contains five genes and three miRNAs. The genes are E4F1, DNASE1L2, ECI1, RNPS1, and ABCA3; miRNAs are MIR3677, MIR940, and MIR4717. The specific deletion has never been previously reported. We describe the phenotype of the boy and review the genes in the deleted region. None of the regulatory elements have any known linkage to skeletal formation and/or maintenance. We believe this deletion is causative given that it was de novo and that this patient cannot be easily explained as having any other specific recognizable pattern of human malformation. 1. Introduction Many of the reports on chromosome 16p13.3 gene deletions are in relation to the Rubinstein-Taybi syndrome, alpha thalassemia mental retardation, polycystic kidney disease, and familial Mediterranean fever. Chromosome 16p13.3 gene deletions associated with the Rubinstein-Taybi syndrome are discussed in depth in articles by Wallerstein et al. and Hennekam et al., respectively [1, 2]. We report a child with developmental delay, bilateral radial ulnar synostosis, Klippel-Feil anomaly, and other vertebral deformities with a de novo interstitial deletion of 114.5？kb on chromosome 16p found using chromosomal microarray. The deleted region contains five genes and three miRNAs of unclear clinical significance. We are not aware of reports of gene deletions that overlap with the 114.5kb deletion described here. The purpose of this paper is to describe our patient’s unique phenotype and discuss the possible genotype-phenotype correlations of the deleted region. 2. Clinical Report Past medical history was significant for term birth with complication of preeclampsia of unknown etiology. He had no neonatal complications. His birth weight was 7 lbs 3？oz. Family history was unremarkable for skeletal disorders. Younger full sibling sister was healthy without issues. The patient had a history of developmental delay and was in an early intervention program in California. He walked around age 2, spoke at age 3, and had phrases around age 4. He also was not toilet trained until age 4. Neurodevelopmental assessment at the age of 8 years showed a Wechsler Intelligence Scale for Children Fourth Edition (WISC IV) verbal comprehension of 89, working memory of 80, perceptional reasoning of 96, processing speed of 83, and low average full scale IQ of 84. He had a history of two febrile seizures,