Karyotype Anomalies in Patients with Disorders of Sexual Development.

OBJECTIVES: Objectives Disorders of sex development(DSD)can result in discordance between the chromosomal and anatomicand/orphenotypic sex of a patient. Reporting patients with uncommon karyotypes associated with DSD is important for clinical comparison of developmental outcomes, and management. Methods We describe three female patients with karyotypes resulting in DSD and the use of a combination of chromosomes and FISH techniques to identify potential causes. Results The first patient was mosaic for idic(Y) that was negative for SRY by FISH. The second patient had idic(Y) that was positive for SRY by FISH. The third patient had an unbalanced translocation between the X chromosome and chromosome 2 [der(2)(X;2)] and XY. These three patients illustrate three different genetic mechanisms underlying DSD. Conclusion Our findings expand the list of abnormal karyotypes that can be associated with DSD and highlight the importance of SRY and DAX1 in phenotypic and functional sexual development.

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.