Partial 3q tetrasomy: Defining the syndrome, neocentromeres, and an additional case report

Partial 3q tetrasomy is an ultra-rare genetic condition, with a phenotype that has hitherto not been comprehensively reviewed. In this paper we report the 18th case and re-evaluate those previously published. The present case presented with dysmorphic features, malformations, cognitive deficits, end-stage renal disease, a surgically corrected tethered chord/scoliosis along with skin pigmentary changes and had remained without a diagnosis for 23 years. Blood and fibroblast karyotyping and exome sequencing yielded a normal result. Chromosomal microarray analysis on uncultured skin biopsies showed a mosaic amplification of the terminal 34 Mb of 3q. Subsequent fluorescence in situ hybridisation on cultured cells showed that a few metaphases contained a small supernumerary marker chromosome (sSMC) consisting of two head-to-head copies of the amplified 3q-material with neocentromere formation, the lower degree of mosaicism in karyotyping being ascribed to loss of sSMC upon culturing. Reviewing the published cases of partial 3q tetrasomy cases we find pigmentary changes along the lines of Blaschko, cognitive deficits, spinal malformations, depressed nasal bridge, and palatal deformities to be frequent findings, and highlight a phenotypic overlap with partial 3q trisomy. Symptoms spanned from mild to severe, likely depending on both the size of the amplification and the degree of mosaicism.