Table 1.
Genetic mutations involved in heterotopic ossification.
| ACVR1 Mutation | ALK2 Domain | Amino Acid Change | Clinical Features |
|---|---|---|---|
| c.617 G>A | GS | R206H | Classical FOP; HO of tendons, ligaments, skeletal muscle; congenital hallux valgus of the great toes; short broad femoral necks; cervical spine fusion; osteochondromas |
| c.605 G>T | GS | R202I | One short great toe; fixed right shoulder and elbow; fusion of neck; relatively late age onset (14 years) |
| c.619 C>G | GS | Q207E | Classical FOP phenotype plus growth retardation with height and weight below the 5th percentile for age |
| c.983 G>A | Kinase | G328E | Severe reduction deformities in all digits; spinal fixation; shoulders fixed in adduction; elbows fixed in flexion; jaw gape; mild cognitive impairment; diffuse scalp hair thinning |
| c.982 G>A | Kinase | G328R | FOP variant; normal toes; short thumbs; no HO during childhood; stooped posture at 30 years of age; hypoplastic cerebellum |
| c.982 G>T | Kinase | G328W | Severe reduction deficits of great toes with lack of toe nails in affected digits; severe malformation of thumb; thin scalp hair and slowed growth rate in second decade of life; sparse eyebrows; mild cognitive impairment with difficulty in abstract thinking; no difficulty in attention span; anatomic abnormalities of the cerebellum |
| c.1067 G>A | Kinase | G356D | Persistence of primary teeth into adulthood; primary amenorrhea; malformation of thumb and great toes |
| c.774 G>C | Kinase | R258S | Absence of great toe malformation; disease onset at age 4 with painful swelling in cervical vertebral region; long remission period; flare-up at age 18 with progressive HO |
| c.1124 G>C | Kinase | R375P | Normal toes; slow progression of disease; flare-ups at age 14; limited motion of spine and shoulders at age 40 |
| c.587 T>C | GS | L196P | No great toe malformation; no heterotopic ossification in skeletal muscle until motorcycle accident at age 21 |
| c.974 G>C | Kinase | G325A | Hallux valgus; late-onset HO provoked by viral illness |
| c.1067 G>A | Kinase | R356D | Slowly progressive respiratory dysfunction and abnormal heterotopic ossification; rigid spine; baldness; sensorineural hearing loss; severe hypodactyly |