Fibrodysplasia Ossificans Progressiva

At a glance

Genetically transmitted malformative syndrome affecting the connective tissue system characterized by heterotopic bond formation and progressive musculoskeletal disability. It is characterized by malformed big toes that are often monophalangic, mild mental retardation, and intermittently progressive ectopic ossification. Preoperative examination revealed multisystem involvement including cranial and cervical ankylosis and severe restrictive lung disease.

Synonyms

Myositis Ossificans; Münchmeyer Disease; Stone Man disease.

Incidence

Incidence is 1:2,000,000 live births and seems to affect both genders equally.

Genetic inheritance

Autosomal dominant. Gene map locus is 4q27-q31.

Pathophysiology

Results from overexpression of a potent bone-inducing morphogen (bone morphogenetic protein 4) in lymphocytes that is responsible for ectopic osteogenesis.

Diagnosis

Mainly clinical, based on the presence of new bone formation in the soft tissue. There is also an increase in alkaline phosphatase during active phase of the disease. Diagnosis established by molecular biology studies (increased levels of bone morphogenetic protein 4 and its mRNA).

Clinical aspects

Symptoms usually appear around 6 years of age and consist of cartilaginous and osteoid transformation of connective tissue. This ectopic bone formation leads to skeletal muscle mass displacement and serious limitation of joint movement, mainly in the elbow, hip, and knee. There is a characteristic hallux deformity, which consists of shortened and angulated halluces with associated brachymesodactyly. Cervical spine involvement is common, with varying degrees of cervical fusion and the possibility of atlantoaxial subluxation. Temporomandibular joint involvement may occur. Muscles of the face, larynx, eyes, anterior abdominal wall, diaphragm, and heart usually escape involvement. Finally, limitation of rib movement may lead to a restrictive, shallow type of breathing but rarely to respiratory failure, although pneumonia is a common complication. ST-segment changes and right bundle branch block are however often seen.

Precautions before anesthesia

Obtain an ECG and pulmonary function testing. Also obtain baseline alkaline phosphatase level. Preoperative examination revealed multisystem involvement including cranial and cervical ankylosis and severe restrictive lung disease. Cervical spine radiography to rule out atlantoaxial subluxation should be done preoperatively.

Anesthetic considerations

Because of the temporomandibular and atlantoaxial involvement, direct laryngoscopy may be difficult and fiberoptic tracheal intubation may be wise. It is recommended to maintain spontaneous ventilation until the tracheal tube has been secured. Proper vascular access must be secured and maintained postoperatively. Positioning of the patient on the operating room table might be more problematic because of the joint limitations. Successful execution of regional techniques may be impossible because of the ectopic bone formation. Also, local trauma may induce more ectopic bone formation. General anesthesia is recommended.

Pharmacological implications

A few patients ...