Aneurysmal bone cysts and pathologic fracture associated with supernumerary ring chromosome 6 in two unrelated patients

• Published in: American journal of medical genetics. Part A Vol. 173; no. 12; pp. 3205 - 3210
• Main Authors: Hurd, Lauren M., Thacker, Mihir M., Okenfuss, Ericka, Duker, Angela L., Lou, Yang, Harty, Mary P., Conard, Katrina, Lian, Jane B., Bober, Michael B.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.12.2017
• Subjects: Aneurysm; bone cysts; Bone imaging; Bone mineral density; Cell lines; Chromosome 6; Chromosomes; Congenital defects; Cysts; Fractures; Genotype & phenotype; Hybridization; mosaic marker chromosome; Mosaicism; osteochondrodysplasias; Osteopenia; pathologic fracture; Patients; Supernumerary; Tetrasomy; mosaic marker chromosome; osteochondrodysplasias; bone cysts; pathologic fracture
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.38498

Small supernumerary ring chromosome 6 (sSRC[6]) is a rare chromosomal abnormality characterized by a broad clinical phenotype. The spectrum of this disorder can range from phenotypically normal to severe developmental delay and congenital anomalies. We describe two unrelated patients with small SRCs derived from chromosome 6 with a novel bone phenotype. Both patients presented with a complex bone disorder characterized by severe osteopenia, pathologic fractures, and cyst‐like lesions within the bone. Imaging revealed decreased bone mineral density, mutiple multiloculated cysts and cortical thinning. Lesion pathology in both patients demonstrated a bland cyst wall with woven dysplastic appearing bone entrapped within it. In patient 1, array comparative genomic hybridization (CGH) detected a tandem duplication of region 6p12.3 to 6q12 per marker chromosome. Cytogenetic analysis further revealed a complex patient of mosaicism with some cell lines displaying either one or two copies of the marker indicative of both tetrasomy and hexasomy of this region. Patient 2 was mosaic for a sSRC that encompassed a 26.8 Mb gain from 6p21.2 to 6q12. We performed an in‐depth clinical analysis of a phenotype not previously observed in sSRC(6) patients and discuss the potential influence of genes located within this region on the skeletal presentation observed.