Short stature as the first manifestation of mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome

Mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome is an autosomal dominant disorder caused by heterozygous mutations in the polymerase, delta 1, catalytic subunit (POLD1) gene. Here, we report the clinical description of a 10-year-old boy who first presented with short stature and hypogonadism. We screened this patient for mutations by focused exome sequencing and verified the results by Sanger sequencing. This boy is the 13th MDPL patient reported with a de novo p.S605del mutation in POLD1 and the first MDPL patient reported in Eastern Asia. Growth hormone (GH) stimulation tests revealed that the patient’s GH level was normal, but the baseline IGF-1 level was extremely low. He was treated with recombinant human growth hormone (rhGH) therapy, which caused accelerated fat loss. Moreover, rhGH therapy might increase the cancer risk; thus, it should be contraindicated in MDPL patients. Therefore, MDPL syndrome is a possible diagnosis in boys with both short stature and hypogonadism, and rhGH therapy should be initiated only when this syndrome is excluded.