Pseudohypoparathyroidism type 1B in a patient conceived by in vitro fertilization: another imprinting disorder reported with assisted reproductive technology

Abstract

Pseudohypoparathyroidism type 1B (PHP1B) is characterized by renal tubular resistance to parathyroid hormone (PTH) leading to hyperphosphatemia, hypocalcemia, elevated PTH, and hyperparathyroid bone changes. PHP1B is an imprinting disorder that results from loss of methylation at the maternal GNAS gene, which suppresses transcription of the alpha subunit of the stimulatory G protein of the PTH receptor. Emerging evidence supports an association between assisted reproductive technologies (ART) and imprinting disorders; however, there is currently little evidence linking PHP1B and ART. We present a twin boy conceived by ART to parents with no history of subfertility who presented at age 12 with bilateral slipped capital femoral epiphysis and bilateral genu valgum deformity. Clinical and laboratory investigation revealed markedly elevated PTH, low ionized calcium, elevated phosphorus, TSH resistance, and skeletal evidence of hyperparathyroidism, leading to the diagnosis of PHP1B. A partial loss of methylation at the GNAS exon A/B locus was observed. The patient’s dizygotic twin sibling was asymptomatic and had normal laboratory evaluation. This is the second reported case of a child with PHP1B conceived by ART, further supporting the possibility that ART may lead to an increased risk for imprinting defects.