Eiken syndrome presenting as pseudohypoparathyroidism due to PTH1R gene pathogenic variant

Abstract Pseudohypoparathyroidism (PHP) is a rare disorder characterized by classic hypocalcemia despite normal or elevated parathyroid hormone (PTH). Pseudohypoparathyroidism is marked by tissue resistance to circulating PTH and is associated with the typical Albright hereditary osteodystrophy (AHO) phenotype, including developmental delay, obesity, short stature, round face, brachydactyly, and ectopic ossifications. Pseudohypoparathyroidism is classified into multiple types based on the extent of clinical features and hormonal resistance beyond the parathyroid glands. We present a 15-year-old boy with recurrent seizures, developmental delay, deafness, poor dentition, and skeletal dysplasia. He did not have the typical AHO phenotype, and investigations revealed severe hypocalcemia, hyperphosphatemia, and elevated PTH, supporting a diagnosis of PHP. Imaging showed bilateral basal ganglia calcification, brachydactyly, clinodactyly, ischiopubic hypoplasia, and skeletal changes beyond those typically observed in patients with typical PHP. Whole-exome sequencing revealed a homozygous missense variant in exon 9 of the PTH1 receptor (PTH1R) gene, suggestive of Eiken syndrome (ES). This variant has not been described in the handful of published cases of ES, and we highlight the rare PTH1R pathogenic variant that leads to PHP and skeletal dysplasia.