Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access
Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc
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Short Communication

Volume 8, Number 3, March 2016, pages 246-253

The Diversity of the Clinical Phenotypes in Patients With Fibrodysplasia Ossificans Progressiva

Figures

Figure 1.
Figure 1. AP radiograph of a 6-month-old girl showed the characteristic shortening and broadening of the first metatarsal which was angulated medially with hypoplasia of the basal phalanx of the first toe - triangular distal phalanx. These features are the earliest in the diagnosis of FOP, making the diagnosis possible before the appearance of soft tissue calcification.
Figure 2.
Figure 2. (a) Congenital flexion deformity of the thumbs is another clue for diagnosis. (b) Severe bilateral and symmetrical shortening of the big toes associated with flexion deformities of the second toes respectively.
Figure 3.
Figure 3. AP thorax radiograph showed the columns and plaques of ectopic bone in a 7-year-old girl with FOP and situs inversus (note the direction of the apex of the heart). Opacities in the muscles and near the tendons insertions were encountered in all patients with progression from proximal to distal and formation of a true bony bridge between various parts of the skeleton was evident (arrows).
Figure 4.
Figure 4. Reformatted CT scan in a 14-year-old girl showed monophalangia with subsequent development of severe shortening of the first metatarsals (secondary to abnormal fusion of the epiphyses).
Figure 5.
Figure 5. (a) Progressive episodes of heterotopic ossifications typically lead to ankylosis of all major joints of the axial and appendicular skeleton, rendering movement impossible. AP radiograph of the knees showed a 13-year-old girl presented with progressive painful limitation of range of motion of the both knees with progressive extra-severe articular ankylosis of the left ankle joint. (b) 3D reconstruction CT scan of the pelvis of the same patient (13-year-old) showed two ossified bands originated from the posterior aspect of the right iliac bone, run downwards and where both got fused and inserted beneath the femoral neck adding extra dilemma to the patient.
Figure 6.
Figure 6. 3D reconstruction CT scan in a 16-year-old girl showed diffuse ankylosing ossification of the inferior margins of the scapulae with that of the spine. On the right side, diffuse ankylosing ossification was noted which extended from the inferior margin of the right scapula with a downward manner to cover the posterior aspect of the ribs (7 - 12) until it got ankylosed with the right margin of S1. On the left side, a longitudinal bar of ossification fused superiorly with the inferior margin of the left scapula with downward extension to involve the posterior aspect of the ribs (6 - 12) and bifurcated to two divisions: one extended upward to involve the shaft of the left humerus (arrow head) and the other branch fused with another bar of ossifcation which run in parallel to other bar, which originated from the spinous process of T11 and extended downwards to fuse with the other ossifcation bar at the level of the spinous process of L4 with eventual formation of a dreadful ankylosis (black arrow) (Fig. 3). These progressive episodes of heterotopic ossifications typically lead to dreadful ankylosis of all major joints of the axial and appendicular skeleton, rendering movement impossible, associated with marked elevation in the alkaline phosphatase level (three times greater than normal).
Figure 7.
Figure 7. 3D reconstruction CT scan of the pelvis in a 15-year-old female patient showed massive heterotopic ossification around the pelvis and the upper shaft of the left femur and the ischium pubis with eventual development of extra-articular ankyloses (firm bridging from the femur to the pelvis) associated with massive ossification of the soft tissue (i.e. heterotopic ossification formed in the soft tissues above and below the greater trochanter of the femur).

Table

Table 1. Diversity of Clinical Presentations in Children and Adults With FOP
 
PatientsAge at which diagnosis was made, sexAge at which soft tissue calcification first notedFindings that led to diagnosisMicrodactyly of big toes and thumbsTorticollisGenetic testing resultsAlkaline phosphatase levelsSurgical proceduresOther manifestations
Patient 16 months old, female-Congenital halux valgus+-Negative for ACVR1 gene mutationNormalNone1) Congenital flexion deformity of the thumbs
2) Unusual stiffness of the spine
Two patients of same age group6 - 11 months old, two males-Congenital hallux valgus+-Positive ACVR1 mutation (R206H)NormalNoneCongenital flexion deformity of the thumbs
Patient 45 years old, femaleThree yearsCongenital hallux valgus+++Was tested primarily for FBN1 gene which was negative. Then, positive for ACVR1 gene mutation (R206H)Two times greater than normalNoneMarfanoid habitus
Two patients same age group7 - 8 years old, two malesFour yearsCongenital hallux valgus-+++Was tested primarily for FBN1 gene and showed negative resultsTwo times greater than normalNoneMarfanoid habitus with extreme stiffness of the spine and pain
Patient 77 years old, femaleThree yearsCongenital hallux valgusNoneTorticollis associated with swellings over the neckPositive ACVR1 gene mutation (R206H)Three times greater than normalNoneMarfanoid habitus associated with painful hips and knees
Patient 814 years old, femaleSeven yearsMonophalangia of the big toesMonophalangia of the big toes++No genetic tests performedThree times greater than normalNonePainful ankylosis of all major joints
Patient 913 years old, femaleTen yearsMonophalangia of the big toesMonophalangia of the big toes++Positive ACVR1 gene mutation (R206H)Three times greater than normalNoneExtra-articular ankylosis of the left knee
Patient 1014 years old, femaleSeven yearsMalformed big toes with superimposed ankyloses of the proximal phalanx with the metatarsal of the first digit of the footSevere microdactyly of the big toes++Was tested primarily for FBN1 gene and showed negativeAlkaline phosphatase levels were four times greater than normal in the period of 10 weeks after the inciting traumaNoneClinically diagnosed as Marfan syndrome
Patient 1116 years old, femaleTen yearsCongenital hallux valgus associated with Marfanoid habitus++-Positive ACVR1 gene mutation (R206H)Alkaline phosphatase levels were four times greater than normal in the period of 12 weeks after the inciting traumaNoneMassive heterotopic ossification around the pelvis and the upper shaft of the left femur and the ischium pubis with eventual development of extra-articular ankyloses