Background: Short stature homeobox (SHOX) gene, located on the pseudoautosomal region of the sex chromosome plays an important role in the development of skeleton and its mutations/deletions can cause skeletal dysplasias.
Objective and hypotheses: We report a male, with Type I Diabetes (T1DM) with Y chromosome deletion and short stature due to the concurrent loss of SHOX.
Method: A 15-year-old boy with T1DM for 6 years was referred for short stature (148.1 cm, −2.62SDS) assessment. His height velocity continued to be poor despite optimisation of his diabetes control. Further investigations to look for other chronic illnesses were normal. A mild body disproportion with an upper and lower segment ratio of 1.3 was noted. He was pubertal with testicular volumes of 810 ml. The IGF1 was normal and the bone age was advanced at 17.5 years.
Results: The skeletal survey showed subtle madelung deformity with mild relative shortening of the ulnar bones and epiphyseal ossification. Microarray analysis showed loss of most of the Y chromosome. Fluorescent in Situ Hybridisation studies using specific centromere probes for X and Y chromosome showed no Y chromosome in 73% of the cell lines and presence of isodicentric Y chromosome, i(Y) with SRY gene in 23% of the cell lines, giving rise to the karyotype 45X/46X, i(Y) The clear male phenotype and short stature in our patient is probably due to degree of mosaicism with higher distribution of i(Y), in the gonads and 45X in the growth plates.
Conclusion: Loss of Y chromosome and resultant deletion of a copy of SHOX in a patient with TIDM has not been previously reported. Infertility can be an associated problem. The skeletal deformities can be subtle in the radiographs with typical bone age advancement. Microarray is helpful as an initial test to detect SHOX deletion.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology