Trichorhinophalangeal syndrome type II (TRPS II) is a rare disease caused by a contiguous gene deletion in the 8q23.3-q24.11 region. Three genes (TRPS1, RAD21, and EXT1) are considered responsible for the most common clinical features, which include facial dysmorphism, ectodermal and skeletal anomalies, osteochondromas, and cognitive impairment. To date, seven patients with 8q23-q24 deletions not involving TRPS1 have been reported, with phenotypes overlapping TRPS II. In this paper, we present clinical and genetic aspects from three non-related patients with 8q23-q24 deletions, and we review the available testing strategies for such patients and their families. The deletions harbored by these patients have been identified through microarray, with two of them also undergoing initial MLPA evaluation. The observed clinical and genetic features are heterogeneous, and generally in keeping with known associations between the three main genes from the deleted region and the clinical manifestations of TRPS II. Particularly, the deleted regions vary substantially in size, genomic coordinates, and gene content, with one not including TRPS1, and another, with a more distal loss, not including either TRPS1 nor RAD21. By describing three new patients, we hope to enlarge the genetic and clinical landscape of TRPS II and 8q23-q24 deletions, and help identify further genotype-phenotype correlations.
Caramizaru et al. (Tue,) studied this question.