Endocrine Abstracts

Introduction: Progressive osseous heteroplasia (POH) is a rare genetic condition of progressive heterotopic ossification (HO), from skin and subcutaneous tissues into deep skeletal muscles. Most cases are caused by heterozygous inactivating mutations of GNAS gene. Related disorders are Albright hereditary osteodystrophy (AHO), pseudohypoparathyroidism (PHP), and primary osteoma cutis. Distinction from other GNAS-based conditions is made by the extension of HO from superficial to deep tissues in POH.

Case report: We present the case of a 10-year-old girl who came to medical attention at 3-months of age for lumbar and scapular subcutaneous ossifications. The biopsy confirmed osseous metaplasia of the connective tissue. The ossification process progressed in size, depth and area, up to painful swelling and mechanical compression in the shoulder. She underwent surgical resection of the scapular lesion at 3-years of age but the ossification recurred 2 years later. There were no congenital hallux valgus or other skeletal deformities. She had clinical features of AHO: round facies, flat nasal bridge, short neck, brachydactyly, obesity. Lab tests revealed mild elevated TSH (4.98 μU/ml) at 5-years of age and later, at 8-years of age, elevated parathyroid hormone (395.9 pg/ml) with hypocalcemia (Ca=8.1 mg/dl) and hyperphosphatemia (P=7.18 mg/dl). She was diagnosed as having PHP most probably type Ia/c based on the typical clinical findings of AHO phenotype and biochemical profile. She received treatment with calcitriol and levothyroxine. Follow-up examinations revealed moderate progression of the heterotopic ossifications and favourable clinical course with spontaneous puberty and no other hormone resistance identified yet at age of 12.

Conclusions: Overlapping features of POH and PHP type I can be present, as part of the spectrum of the heterogeneous GNAS related disorders. Awareness and distinction of these conditions are important for appropriate management.