The syndrome is hereditary without sex predilection. Unaffected family members may have the toe deformities without the subsequent ectopic ossification. The name of the disease indicates its histologic resemblance to the ectopic ossification found in other forms of myositis ossificans (see Section 6, Plate 6-24).

Clinical Manifestations. Congenital anomalies of the digits are initially noted at birth. Hypoplasia of the great toes is the most common manifestation, with great toe microdactyly occurring in 90% of patients. A similarly high association occurs with marked hallux valgus. Less common, microdactyly of the thumb occurs in 50% of patients.

The average age at onset is 5 years old, with characteristic localized swellings arising in the neck, back, and limbs, often accompanied by considerable tenderness, pyrexia, and occasionally draining ulcers. The ossification develops somewhat later and may cause ankylosis of the vertebral bodies and joints such as the elbow, knee, hip, and shoulder. By the midadolescent years, 95% of patients have severely restricted upper extremity range of motion. Despite the marked upper extremity involvement, the most debilitating effects are seen in the jaw muscles (inhibiting jaw motion) and chest muscles (impairing chest wall expansion and breathing). Fortunately, the tongue, diaphragm, and sphincters are not involved. Spinal involvement is common, with 65% of patients displaying scoliosis features.

Treatment. There are limited options for treatment. Clinical diagnosis is important, because surgical biopsy or excision only create robust recurrence. Supportive measures to ensure adequate nutrition and respiration may be needed, owing to the involvement of mastication and chest wall musculature. Patient falls can cause severe flareups or lifelong disability. Cervical involvement can make anesthesia management difficult. Current efforts with targeted gene therapy and bone morphogenetic protein antagonists have shown future promise. At this point, treatment measure are mainly supportive, ensuring proper nutrition, fall prevention, and pain control. Despite a marked disability, patients with fibrodysplasia ossificans progressiva can survive for many years.

PROGRESSIVE DIAPHYSEAL DYSPLASIA (ENGELMANN DISEASE)

This autosomal dominant hereditary disorder is characterized by a bilateral and symmetric cortical thickening of long bone diaphyses. The genetic pattern displays variable penetrance, with the disease becoming manifest in childhood as neuromuscular dystrophy. The child walks with legs spread apart, imparting a peculiar waddling gait. Generalized weakness and fatigability, along with delayed growth and sexual development, are commonly seen. Involvement of the skull in 60% of patients may lead to optic and auditory nerve entrapment.

With progression of the disease, the diameter of the diaphysis enlarges and the medullary canal becomes increasingly narrowed. The lesions spread proximally and distally toward the epiphyses. With the near obliteration of the medullary canals, hematopoiesis is diminished, resulting in secondary anemia and hepatomegaly.

Diagnostic Studies. Typical radiographic findings include (1) symmetric skeletal distribution; (2) fusiform enlargement of the diaphysis of the long bones and amorphous increase in density at the base of the skull; (3) thickening of the cortex by both periosteal and endosteal accretion of mottled bone without a recognizable trabecular pattern; (4) abrupt demarcation of the lesion; (5) progression of the lesion proximally and distally along the long axis of the bone with gradual alteration of the previously normal cortical bone; (6) relative elongation of the limb; (7) changes in soft tissue associated with underdevelopment and malnutrition; and (8) normal epiphyses and metaphyses.

Histologic examination shows that bone formation is increased on both the periosteal and endosteal surfaces. The increased osteoclastic and osteoblastic activity in the affected area destroys much of the lamellar bone and lays down large amounts of irregularly arranged trabecular bone, increasing the bone porosity.

Treatment. The only treatment for this disorder is symptomatic care. Good nutrition is essential in the treatment of secondary anemia, and blood transfusions may be needed. Anti-inflammatory medication (including corticosteroids) aids with symptomatic pain relief, with physical therapy being a staple part of treatment to increase strength and preserve joint motion. Bisphosphonates have been shown to correlate with increased bone pain in patients with progressive diaphyseal dysplasia.