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

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. © 2008 Wiley‐Liss, Inc.