ESPE Abstracts

Background: Skeletal dysplasia is the main cause of disproportionate short stature. The severity may vary. The present patient had disproportionate short stature with brachydactyly.

Patient and method: A boy of 5 years old presented with height 108.9 cm (−1.8 S.D.), sitting height/height ratio was +3.4 S.D., short hands and feet with short metacarpal 4 and metatarsal 4 on both sides. He had increased lumbar lordosis and painful legs after walking of a long distance. The mother had a height of 150.6 cm (−3.0 S.D.) and father 179.9 cm (−0.4 S.D.). The mother had a disproportionate short stature and brachydactyly. The boy was born from a twin pregnancy after an amenorrhea duration of 34 weeks, birth weight 1740 g (−1.4 S.D.) with a moderate start. His twin sister is healthy. His development was retarded. His bone age was 3 years advanced. Additional laboratory assessment showed normal serum calcium, phosphate, alkaline phosphatase, parathyroid hormone (PTH) and immeasurable PTH-related protein (PTH-rp). DNA analysis was performed. He had no mutation in the FGFR3 gene, no mutation/deletion/duplication of the SHOX or COL2A1 genes and a normal array CGH.

Results and discussion: DNA analysis showed a mutation in exon 4 of the (PTH-like hormone) PTHLH gene (c.25T>C, p.Trp9Arg). The mutation was also found in the mother, but not in her parents, the mutation had therefore occurred de novo in the mother. A GNAS gene mutation was excluded in the mother. Other PTHLH mutations have been described in patients with short stature and brachydactyly type E. PTH-rp acts through the PTH-receptor and is essential for normal cartilage development. Failure of this activation leads to increased chondrocyte apoptosis and premature closure of the growth plates.

Conclusion: Disproportionate short stature with advanced bone age may be caused by a PTHLH mutation.