Esra Eraslan AYDEMİR, Şerife Özkarakoç ERTÜRK, Can Berk LEBLEBİCİ, Halil Gürhan KARABULUT, Özgür DEMİR
Endocrinology Research and Practice - 2026;30(3):213-216
X-linked hypophosphatemia (XLH) is the most common inherited form of hypophosphatemic rickets, caused by inactivating mutations in the phosphate-regulating endopeptidase homolog, X-linked (PHEX) gene. Despite its distinct clinical and biochemical features, XLH can be misdiagnosed as achondroplasia because of overlapping skeletal manifestations. Two sisters, aged 53 and 60 years, who were misdiagnosed with achondroplasia for more than 5 decades were later diagnosed with XLH. Both patients presented with diffuse bone pain, severe skeletal deformities, including coxa vara with shepherd's crook deformity and femoral bowing and a history of spontaneous dental abscesses. Laboratory testing revealed hypophosphatemia with normocalcemia. Family history showed an X-linked dominant inheritance pattern, with an affected father, all 4 sisters affected, and 3 unaffected brothers-inconsistent with achondroplasia. Whole-exome sequencing identified a novel heterozygous PHEX variant, c.207_212del (p.K69_V70del), classified as a variant of uncertain significance (VUS) per American College of Medical Genetics (ACMG) guidelines. Notably, the first patient had undergone parathyroidectomy 24 years earlier, likely reflecting tertiary hyperparathyroidism as a long-term complication of undiagnosed XLH. This report highlights that careful evaluation of family history, combined with simple biochemical tests, can prevent decades of misdiagnosis and its associated morbidity.
