Fibrodysplasia ossificans progressiva (FOP). Myositis ossificans progressiva.
Incidence
It is an ultra-rare genetic disorder. It has an estimated prevalence of 1.36 people per million. It has no racial, ethnic or geographic predisposition. It is related to a gain-of-function point mutation in the ALK2/ACVR1 gene. It is often confused with other more common conditions.
Clinical Characteristics
This condition is a rare and disabling genetic condition of congenital skeletal malformations and progressive heterotopic ossification (HO), possible one of the most catastrophic disorders of HO in humans. Two clinical features define classic FOP: bilateral malformation of the great toes and progressive heterotopic ossification. Other frequently observed signs include short malformed thumbs and early developmental abnormalities in the cervical spine. Other skeletal abnormalities can lead to difficulty eating, hearing impairment, and life threatening cardiopulmonary complications. Approximately 50% of patients experience progressive hearing impairment. Many patients are confined to wheelchair by the third decade of life. Median age of death is 45 years, commonly from complications of thoracic insufficiency syndrome. Definitive diagnosis of FOP can be made by direct clinical evaluation and can be confirmed by DNA diagnostic testing of the ACVR1 gene. The primary molecular pathology involves the bone morphogenetic protein (BMP) signaling pathway, and an overactivity of this pathway is the underline cause of the ectopic chondrogenesis, joint fussion and osteogenesis seen in FOP. The condition is characterized by flare-ups that often lead to progressive heterotopic ossifications (HO) with abnormal and irreversible formation of bone in muscles, tendons and ligaments. So it is a condition where soft tissue turns to bone, often related to a triggering event, like surgeries done on the lesions, IM injections, biopsies, etc.
Precipitants
There are often triggering events, like surgeries done on the lesions, IM injections, biopsies, etc. All these procedures precipitate flare ups and increase the heterotopic bone formation in those areas.
Provocation Tests
None.
Diagnostic Procedures
Definitive diagnosis of FOP can be made by direct clinical evaluation and can be confirmed by DNA diagnostic testing of the ACVR1 gene.