Autosomal dominant pseudohypoparathyroidism type 1b due to STX16 deletion: a case presentation and literature review.

Introduction: Pseudohypoparathyroidism (PHP) is a heterogeneous group of rare, genetically related, endocrine disorders, characterized by end-organ resistance to parathyroid hormone (PTH) action and other G protein-coupled receptors (GPCRs) related hormones. The clinical variants of PHP are classified according to the presence of features of Albright's hereditary osteodystrophy (AHO) and in vivo response to exogenous PTH. Autosomal dominant PHP1b is often caused by a deletion in the syntaxin-16 (STX16) gene, leading to a loss of methylation in the A/B exon of the guanine nucleotide-binding protein a-stimulating polypeptide (GNAS) complex. Herein, we present a case of a 41-year-old man with familiar PHP1b due to a maternal inherited 3-kb STX16 deletion, who was referred to us for consultation by artificial reproductive technology specialists.

Evidence acquisition: A bibliographic search was performed in electronic databases (PubMed and Cochrane Library) to identify similar cases.

Evidence synthesis: Twenty studies (case-series or reports) were eligible. These studies included collectively 120 patients; 46 patients (38.3%) presented with symptoms of hypocalcemia; 38 were asymptomatic (31.7%); data for 36 patients (30%) were unavailable. Thyroid-stimulating hormone (TSH) resistance was documented in 25 occasions (21%); growth hormone deficiency in 2 (1.7%); 3 patients shared features of the AHO (2.5%); 6 had abnormal bone mineral density test (5%). Notable is the development of tertiary hyperparathyroidism in 3 individuals (2.5%).

Conclusions: The present review confirms the heterogeneity in the clinical spectrum of familiar PHP1b. Future research should focus on the molecular characterization of the GNAS disorders, leading to a facile diagnosis and appropriate genetic counseling.