Background: Progressive osseous heteroplasia (POH) is a rare condition characterized by extensive heterotopic ossification (HO) of connective tissues. Associations of HO and Albright hereditary dystrophy (AHO) lead to the identification of GNAS mutations to be causative for ectopic none formations. The highly imprinted GNAS locus is known to cause a broad spectrum of pathologic conditions, including pseudohypoparathyrodism (PHP), pseudoPHP AHO. While PHP is caused by maternal inheritance, paternal inheritance leads to pseudoPHP and POH. Only a small subpopulation of patients with maternally inherited GNAS mutations has been reported to feature HO.
Objective and hypotheses: Here, we report the case of a 10-year-old boy with PHP1a, featuring extensive dermal ossification at multiple locations. In contrast to reported mild ectopic ossification in PHP1a patients, this case shows the potentially progressive character of HO despite maternal inheritance of a GNAS mutation.
Method: The patients history including genetic analysis, lab and imaging findings as well as treatments are reported.
Results: Genetic analysis of the GNAS locus has been performed in the patient and both parents, excluding a paternal inheritance. In the course of treatment, both extensions of existing lesions as well as occurrence of new lesions were observed despite treatment and serum calcium levels within the target range. While being progressive in size and number of lesions, HO in our patient has been shown to be limited to the dermis which is in line with the small number of similar cases.
Conclusion: We hereby report the occurrence of severe heterotopic ossification in a patient with a maternally inherited GNAS mutation and PHP1a. Despite serum calcium levels in the target range, bone formation remains progressive raising the need of specific treatments for this impairing symptom.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology