A novel missense variant in TRAPPC2 causes X-linked spondyloepiphyseal dysplasia tarda: A case report

X-linked spondyloepiphyseal dysplasia tarda (X-linked SEDT) is a rare hereditary cause in childhood short stature due to mutations in trafficking protein particle complex subunit 2 (TRAPPC2) gene located on chromosome Xp22. Several pathogenic variants in TRAPPC2 have been reported, but missense variants are rare.

A 13-year, 8-month-old Chinese Han boy presenting with short stature for the past 7 years.

X-linked SEDT was established by a combination of clinical and radiographic features, confirmed by targeted next-generation sequencing. Genetic testing of the TRAPPC2 gene revealed a novel missense variant with c.260A>C (p.H87P) hemizygote in exon5. The mother was found to be a heterozygous TRAPPC2 carrier, whereas the father was normal.

Patient was treated with recombinant human growth hormone daily. Patient's height, glucose level, and possible progressive joint and back pain with osteoarthritis were under intensive observation regularly.

The patient achieved 2.1 cm height gain over the first 3 months' recombinant human growth hormone treatment without joint or back pain. However, the therapy was terminated because of increased glucose level on follow-up.

The short stature is a noteworthy problem for X-linked SEDT cases. We report a novel missense variant site in TRAPPC2 treated with growth hormone in the literature. We do not recommend the use of recombinant human growth hormone on patients with X-linked SEDT for the concern of glucose homeostasis.