Unique coexistence of SHOX and PTHLH gene mutations in a 12-year-old boy with syndromic short stature. Case report with literature review

Abstract

Despite the availability of advanced genetic testing that enables accurate and reliable genotype assessment, clinicians continue to face diagnostic problems, especially in patients with potentially pathogenic mutations in different genes. SHOX gene mutations are the most common cause of proportional monogenic short stature, whereas the PTHLH gene encodes a parathormone-related protein that plays a crucial role in the regulation of cell growth, calcium ion transport, and bone development. The authors present the case of a 12-year-old boy with a short stature and a mosaic of developmental malformations; nephrocalcinosis; and calcium and magnesium metabolism disorders; with a unique coexistence of mutations in the SHOX and PTHLH genes. The presented case extends the clinical spectrum associated with these rare mutations and shows the usefulness of whole exome sequencing in diagnosing patients with atypical phenotypes.