Clinical and genetic features, surgical management, and longitudinal follow-up in two children with progressive osseous heteroplasia.

Background: Progressive osseous heteroplasia (POH) is an ultrarare disorder characterized by heterotopic ossification that progresses from the skin and subcutaneous tissues into deeper connective tissues. Most affected individuals harbor heterozygous inactivating variants in Methods: We retrospectively characterized two children with clinically diagnosed POH who underwent genetic testing and surgical treatment. Whole-exome sequencing was performed on peripheral blood and, when available, resected tissue, followed by PCR-Sanger sequencing and T-vector cloning. Case 1 underwent clinical and radiographic follow-up for 5 years; follow-up for Case 2 was limited to family-provided radiographs obtained at 2 years. Results: Case 1 harbored a possible postzygotic mosaic Conclusion: These cases provide additional clinical, molecular, and longitudinal information on POH and illustrate the importance of lesion distribution and resectability when interpreting surgical outcomes. The available postoperative findings cannot establish a causal relationship between variant status and prognosis because the patients differed in baseline disease extent, completeness of excision, follow-up duration, and outcome ascertainment. A possible association between mosaic burden and lesion distribution remains a hypothesis that requires evaluation in larger cohorts.