Clinical and molecular characterization of a patient with Langer–Giedion syndrome and mosaic del(8)(q22.3q24.13)

Abstract

The tricho-rhino-phalangeal syndrome type II (TRPS II) is characterized by sparse scalp hair, a long nose with a bulbous tip, a long flat philtrum, cone-shaped epiphyses of the phalanges, retarded bone age in infancy and multiple cartilaginous exostoses. All patients have a hemizygous deletion on chromosome 8q23.3-24.11 which spans at least the 2.8 Mb-region from TRPS1 through EXT1. Only patients with deletions that extend beyond this interval tend to have mental retardation. Here we describe a 14.5-year-old girl with mental retardation and TRPS II. Her facial features are only mild, but she has the typical skeletal features including cone-shaped epiphyses at the phalanges, retarded bone age, multiple exostoses and short stature. She is the first patient with TRPS II and a molecularly proven mosaic interstitial deletion in 8q22.3-q24.13. The deletion is one of the largest ever found in TRPS II, and spans 19.79 Mb and 50 genes or loci including TRPS1 and EXT1. The degree of mosaicism is 7% in lymphocytes from peripheral blood and 97% in skin fibroblasts.