Progressive osseous heteroplasia: A case report with an unexpected trigger

Area of Science:

• Genetics
• Pathology
• Biochemistry

Background:

• Progressive osseous heteroplasia (POH) is a rare genetic disorder characterized by heterotopic ossification (HO) in skin and subcutaneous tissues.
• It is caused by inactivating mutations in the GNAS gene and typically manifests in infancy.

Observation:

• A case report of a preterm male infant presenting with subcutaneous calcium deposits after parenteral nutrition extravasation.
• Skin biopsy confirmed intramembranous ossification, and genetic testing identified a novel, de novo, heterozygous nonsense variant in the GNAS gene.

Findings:

• The identified GNAS variant aligns with the clinical diagnosis of POH.
• This case is the first to report an inflammatory trigger in POH, with no associated endocrine abnormalities or overlapping conditions.
• Intravenous bisphosphonate, glucocorticoid, and topical sodium thiosulfate treatments showed no clinical improvement.

Implications:

• This case expands the known phenotypic spectrum of GNAS mutation disorders.
• It suggests that anti-inflammatory treatments might be beneficial for POH.
• GNAS mutations should be considered in patients with progressive calcium deposition following extravasation injuries.