Pseudohypoparathyroidism Type 1A in an Omani Family Demonstrating Phenotypic Heterogeneity and Progressive...

Pseudohypoparathyroidism type 1A (PHP1A) is an uncommon inherited condition caused by loss‑of‑function mutations in the guanine nucleotide-binding protein, alpha-stimulating activity polypeptide (GNAS) gene, which results in hormone resistance to parathyroid hormone (PTH) and other hormones that signal through the stimulatory alpha subunit of the G protein (Gsα). The disorder is classically associated with Albright hereditary osteodystrophy (AHO), although marked phenotypic and biochemical variability has been increasingly recognized, particularly in children. We report three siblings from an Omani family diagnosed with PHP1A, aged 2.6-9 years, demonstrating substantial intrafamilial heterogeneity. The eldest sibling presented with severe multisystem involvement, including congenital aortic stenosis, extensive osteoma cutis, and neurocognitive impairment. The proband had a more classical endocrine phenotype with progressive PTH elevation and symptomatic soft tissue ossifications. The youngest sibling was identified through family screening during infancy and remained largely asymptomatic despite evolving biochemical abnormalities. All siblings demonstrated characteristic AHO features including round facies, brachydactyly, and shortening of the fourth and fifth metacarpals and metatarsals. Longitudinal biochemical evaluation showed progressive PTH elevation with persistent normocalcemia and hyperphosphatemia. Genetic testing in one sibling confirmed a heterozygous pathogenic GNAS mutation. This familial case series highlights the broad phenotypic spectrum and dynamic biochemical evolution of PHP1A. AHO manifestations may precede overt biochemical abnormalities for several years, particularly during childhood. Recognition of subtle early features, proactive family screening, and longitudinal biochemical monitoring are essential for timely diagnosis and management.