title: Endochondral ossification in a case of progressive osseous heteroplasia in a young female child.
abstract: Progressive osseous heteroplasia (POH) (OMIM 166350) is a rare autosomal dominant condition, characterized by heterotopic ossification of the skin, subcutaneous fat, and deep connective tissue. This condition is distinct from Albright's hereditary osteodystrophy or McCune Albright syndrome (OMIM 103580) and fibrodysplasia ossificans progressiva (OMIM 135100). We present an unusual presentation of POH in a 7-year-old female child. The clinical features included a painful swelling on the left foot, with mechanical complaints. There was no congenital hallux valgus. Family anamnesis was positive in the father. There were subcutaneous ossifications of his left upper arm, right-sided thorax, and lateral side of the right ankle. The father did not allow any radiographs or further examinations. Radiographic examination of the patient revealed ossified subcutaneous plaques on the left foot, lumbar spine, and left scapulae. Additional blood samples were analyzed, revealing no pseudohypoparathyroidism. Sequence analysis of the gene associated with POH, the GNAS1 gene, revealed the heterozygote mutation c.565_568del, previously found in Albright's hereditary osteodystrophy. Histopathological examination of the subcutaneous ossification showed presence of chondrocyte clusters, a feature usually found in fibrodysplasia ossificans progressiva. The combination of the clinical features, the absence of pseudohypoparathyroidism, histology revealing chondrocyte clusters, and the specific GNAS mutation in this patient makes this a truly unusual presentation of POH. The findings in the described case might denote subdivisions of POH. The condition is associated with progressive superficial to deep ossification, progressive restriction of range of motion, and recurrence if excised. We hope to inform pediatricians and orthopedic surgeons to create more awareness of this disorder so that unnecessary treatments can be avoided and proper counseling offered.
authors.affiliation: Departments of aOrthopedics bPediatrics cClinical Genetics, Maastricht Universitair Medisch Centrum+, Maastricht University dGROW School for Oncology and Developmental Biology, Maastricht University eCAPHRI School for Public Health and Primary Care, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Dirk E
authors.initials: DE
authors.lastname: Schrander
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Welting
authors.forename: Marjolein M J
authors.initials: MM
authors.lastname: Caron
authors.forename: Jaap J P
authors.initials: JJ
authors.lastname: Schrander
authors.forename: Lodewijk W
authors.initials: LW
authors.lastname: van Rhijn
authors.forename: Inge
authors.initials: I
authors.lastname: Körver-Keularts
authors.forename: Constance T R M
authors.initials: CT
authors.lastname: Schrander-Stumpel
mesh_terms: D001851:Bone Diseases, Metabolic / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D002648:Child; D020219:Chondrogenesis; D002864:Chromogranins; D005260:Female; D005528:Foot / Q000473:pathology; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics; D006801:Humans; D009999:Ossification, Heterotopic / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D012873:Skin Diseases, Genetic / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology
chemical_list: D002864:Chromogranins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs