A prospective study of radiographic manifestations in Hutchinson-Gilford progeria syndrome

Abstract

Background: Progeria is a rare segmental premature aging disease with significant skeletal abnormalities. Defining the full scope of radiologic abnormalities requires examination of a large proportion of the world's progeria population (estimated at 1 in 4 million). There has been no comprehensive prospective study describing the skeletal abnormalities associated with progeria.

Objective: To define characteristic radiographic features of this syndrome.

Materials and methods: Thirty-nine children with classic progeria, ages 2-17 years, from 29 countries were studied at a single site. Comprehensive radiographic imaging studies were performed.

Results: Sample included 23 girls and 16 boys-the largest number of patients with progeria evaluated prospectively to date. Eight new and two little known progeria-associated radiologic findings were identified (frequencies of 3-36%). Additionally, 23 commonly reported findings were evaluated. Of these, 2 were not encountered and 21 were present and ranked according to their frequency. Nine abnormalities were associated with increasing patient age (P = 0.02-0.0001).

Conclusion: This study considerably expands the radiographic morphological spectrum of progeria. A better understanding of the radiologic abnormalities associated with progeria and improved understanding of the biology of progerin (the molecule responsible for this disease), will improve our ability to treat the spectrum of bony abnormalities.

Figures

Fig 1

a: 5 year old girl with Progeria and a cortical notch defect: Cortical notch defects when present in the radius were always situated in the proximal diaphysis along the ulnar aspect, essentially at the site of the radial tuberosity (arrow). b: 10 year old girl with Progeria and a cortical notch defect: When present in the tibia, the cortical notch defects were in the anterior cortex of the proximal diaphysis somewhat below the level of the normal concavity associated with the tibial tubercle apophysis (arrow indicates the tibial tubercle; arrowhead indicates the abnormal cortical notch). c: 5 year old girl with Progeria and a cortical notch defect: The defect was always similarly placed in the anterior proximal diaphysial cortex when present in the tibia (arrow). d: 9 year old boy with Progeria and a cortical notch defect: When the greater trochanter was enlarged and elongated, it often had a laterally placed notch defect (arrows). (Also note the presence of hip dysplasia, coxa valga and moderately enlarged proximal femurs.) e: 5 year old girl with Progeria and a cortical notch defect: When present in the femoral neck, cortical notch defects were situated in the mid aspect of the medial margin, as noted on the left in this child (arrow). (Also note the presence of hip dysplasia, coxa valga and moderately enlarged proximal femurs.) f: 10 year old girl with Progeria and a cortical notch defect: One patient had a cortical notch defect in the proximal anterior diaphysis of the right humerus (arrow). There is questionable partial internal ossification.

Fig 1

a: 5 year old girl with Progeria and a cortical notch defect: Cortical notch defects when present in the radius were always situated in the proximal diaphysis along the ulnar aspect, essentially at the site of the radial tuberosity (arrow). b: 10 year old girl with Progeria and a cortical notch defect: When present in the tibia, the cortical notch defects were in the anterior cortex of the proximal diaphysis somewhat below the level of the normal concavity associated with the tibial tubercle apophysis (arrow indicates the tibial tubercle; arrowhead indicates the abnormal cortical notch). c: 5 year old girl with Progeria and a cortical notch defect: The defect was always similarly placed in the anterior proximal diaphysial cortex when present in the tibia (arrow). d: 9 year old boy with Progeria and a cortical notch defect: When the greater trochanter was enlarged and elongated, it often had a laterally placed notch defect (arrows). (Also note the presence of hip dysplasia, coxa valga and moderately enlarged proximal femurs.) e: 5 year old girl with Progeria and a cortical notch defect: When present in the femoral neck, cortical notch defects were situated in the mid aspect of the medial margin, as noted on the left in this child (arrow). (Also note the presence of hip dysplasia, coxa valga and moderately enlarged proximal femurs.) f: 10 year old girl with Progeria and a cortical notch defect: One patient had a cortical notch defect in the proximal anterior diaphysis of the right humerus (arrow). There is questionable partial internal ossification.

Fig 1

a: 5 year old girl with Progeria and a cortical notch defect: Cortical notch defects when present in the radius were always situated in the proximal diaphysis along the ulnar aspect, essentially at the site of the radial tuberosity (arrow). b: 10 year old girl with Progeria and a cortical notch defect: When present in the tibia, the cortical notch defects were in the anterior cortex of the proximal diaphysis somewhat below the level of the normal concavity associated with the tibial tubercle apophysis (arrow indicates the tibial tubercle; arrowhead indicates the abnormal cortical notch). c: 5 year old girl with Progeria and a cortical notch defect: The defect was always similarly placed in the anterior proximal diaphysial cortex when present in the tibia (arrow). d: 9 year old boy with Progeria and a cortical notch defect: When the greater trochanter was enlarged and elongated, it often had a laterally placed notch defect (arrows). (Also note the presence of hip dysplasia, coxa valga and moderately enlarged proximal femurs.) e: 5 year old girl with Progeria and a cortical notch defect: When present in the femoral neck, cortical notch defects were situated in the mid aspect of the medial margin, as noted on the left in this child (arrow). (Also note the presence of hip dysplasia, coxa valga and moderately enlarged proximal femurs.) f: 10 year old girl with Progeria and a cortical notch defect: One patient had a cortical notch defect in the proximal anterior diaphysis of the right humerus (arrow). There is questionable partial internal ossification.

Fig 1

a: 5 year old girl with Progeria and a cortical notch defect: Cortical notch defects when present in the radius were always situated in the proximal diaphysis along the ulnar aspect, essentially at the site of the radial tuberosity (arrow). b: 10 year old girl with Progeria and a cortical notch defect: When present in the tibia, the cortical notch defects were in the anterior cortex of the proximal diaphysis somewhat below the level of the normal concavity associated with the tibial tubercle apophysis (arrow indicates the tibial tubercle; arrowhead indicates the abnormal cortical notch). c: 5 year old girl with Progeria and a cortical notch defect: The defect was always similarly placed in the anterior proximal diaphysial cortex when present in the tibia (arrow). d: 9 year old boy with Progeria and a cortical notch defect: When the greater trochanter was enlarged and elongated, it often had a laterally placed notch defect (arrows). (Also note the presence of hip dysplasia, coxa valga and moderately enlarged proximal femurs.) e: 5 year old girl with Progeria and a cortical notch defect: When present in the femoral neck, cortical notch defects were situated in the mid aspect of the medial margin, as noted on the left in this child (arrow). (Also note the presence of hip dysplasia, coxa valga and moderately enlarged proximal femurs.) f: 10 year old girl with Progeria and a cortical notch defect: One patient had a cortical notch defect in the proximal anterior diaphysis of the right humerus (arrow). There is questionable partial internal ossification.

Fig 1

a: 5 year old girl with Progeria and a cortical notch defect: Cortical notch defects when present in the radius were always situated in the proximal diaphysis along the ulnar aspect, essentially at the site of the radial tuberosity (arrow). b: 10 year old girl with Progeria and a cortical notch defect: When present in the tibia, the cortical notch defects were in the anterior cortex of the proximal diaphysis somewhat below the level of the normal concavity associated with the tibial tubercle apophysis (arrow indicates the tibial tubercle; arrowhead indicates the abnormal cortical notch). c: 5 year old girl with Progeria and a cortical notch defect: The defect was always similarly placed in the anterior proximal diaphysial cortex when present in the tibia (arrow). d: 9 year old boy with Progeria and a cortical notch defect: When the greater trochanter was enlarged and elongated, it often had a laterally placed notch defect (arrows). (Also note the presence of hip dysplasia, coxa valga and moderately enlarged proximal femurs.) e: 5 year old girl with Progeria and a cortical notch defect: When present in the femoral neck, cortical notch defects were situated in the mid aspect of the medial margin, as noted on the left in this child (arrow). (Also note the presence of hip dysplasia, coxa valga and moderately enlarged proximal femurs.) f: 10 year old girl with Progeria and a cortical notch defect: One patient had a cortical notch defect in the proximal anterior diaphysis of the right humerus (arrow). There is questionable partial internal ossification.

Fig 1

a: 5 year old girl with Progeria and a cortical notch defect: Cortical notch defects when present in the radius were always situated in the proximal diaphysis along the ulnar aspect, essentially at the site of the radial tuberosity (arrow). b: 10 year old girl with Progeria and a cortical notch defect: When present in the tibia, the cortical notch defects were in the anterior cortex of the proximal diaphysis somewhat below the level of the normal concavity associated with the tibial tubercle apophysis (arrow indicates the tibial tubercle; arrowhead indicates the abnormal cortical notch). c: 5 year old girl with Progeria and a cortical notch defect: The defect was always similarly placed in the anterior proximal diaphysial cortex when present in the tibia (arrow). d: 9 year old boy with Progeria and a cortical notch defect: When the greater trochanter was enlarged and elongated, it often had a laterally placed notch defect (arrows). (Also note the presence of hip dysplasia, coxa valga and moderately enlarged proximal femurs.) e: 5 year old girl with Progeria and a cortical notch defect: When present in the femoral neck, cortical notch defects were situated in the mid aspect of the medial margin, as noted on the left in this child (arrow). (Also note the presence of hip dysplasia, coxa valga and moderately enlarged proximal femurs.) f: 10 year old girl with Progeria and a cortical notch defect: One patient had a cortical notch defect in the proximal anterior diaphysis of the right humerus (arrow). There is questionable partial internal ossification.

Fig 2

a: 17 year old boy with Progeria and dystrophic calcifications: Dystrophic soft tissue calcifications were seen over the chest, abdomen, and extremities. They were often linear, curvilinear or clumped (as in this child’s lower leg)(arrow). b: 3 year old girl with Progeria and dystrophic calcifications: When calcifications were adjacent to the digital tufts, they frequently were “popcorn” like in their configuration as seen in the second digit. (Also note variable degrees of acroosteolysis of the tufts.)

Fig 2

a: 17 year old boy with Progeria and dystrophic calcifications: Dystrophic soft tissue calcifications were seen over the chest, abdomen, and extremities. They were often linear, curvilinear or clumped (as in this child’s lower leg)(arrow). b: 3 year old girl with Progeria and dystrophic calcifications: When calcifications were adjacent to the digital tufts, they frequently were “popcorn” like in their configuration as seen in the second digit. (Also note variable degrees of acroosteolysis of the tufts.)

Fig 3

a: 8 year old boy with Progeria with ulnar minus variant: There is relative foreshortening of the ulna consistent with mild ulnar minus variant. (Also note variable degrees of acroosteolysis of the tufts.) b: 10 year old girl with Progeria with Madelung like deformity: There is a mildly angular contour formed by the distal radius and ulna, with the median aspects of each sloping proximally, consistent with a mild Madelung’s deformity. Also note variable degrees of acroosteolysis of the tufts and dystrophic calcifications distal to several of the tufts.

Fig 3

a: 8 year old boy with Progeria with ulnar minus variant: There is relative foreshortening of the ulna consistent with mild ulnar minus variant. (Also note variable degrees of acroosteolysis of the tufts.) b: 10 year old girl with Progeria with Madelung like deformity: There is a mildly angular contour formed by the distal radius and ulna, with the median aspects of each sloping proximally, consistent with a mild Madelung’s deformity. Also note variable degrees of acroosteolysis of the tufts and dystrophic calcifications distal to several of the tufts.

Fig 4

a: 17 year old boy with Progeria with enlarged proximal humerus: The proximal humerus is moderately enlarged bilaterally. (Also note narrow pulmonary apices, small clavicles with distal resorption, thin ribs with anterior resorption and cardiomegaly.) b: 12 year old boy with Progeria with enlarged proximal and distal humerus: This patient shows mild enlargement of the proximal humerus with comparable enlargement of the distal humerus, particularly laterally. The diaphysis is mildly narrowed. (Also note pseudoarthrosis of the distal clavicle.) c: 4 year old sister of patient in figure 4b who also has Progeria: This image, in comparison to figure 4c, reveals normally sized proximal and distal humerus without diaphyseal narrowing. (Also note mild resorption of the distal clavicle which is mildly narrowed.)

Fig 4

a: 17 year old boy with Progeria with enlarged proximal humerus: The proximal humerus is moderately enlarged bilaterally. (Also note narrow pulmonary apices, small clavicles with distal resorption, thin ribs with anterior resorption and cardiomegaly.) b: 12 year old boy with Progeria with enlarged proximal and distal humerus: This patient shows mild enlargement of the proximal humerus with comparable enlargement of the distal humerus, particularly laterally. The diaphysis is mildly narrowed. (Also note pseudoarthrosis of the distal clavicle.) c: 4 year old sister of patient in figure 4b who also has Progeria: This image, in comparison to figure 4c, reveals normally sized proximal and distal humerus without diaphyseal narrowing. (Also note mild resorption of the distal clavicle which is mildly narrowed.)

Fig 4

a: 17 year old boy with Progeria with enlarged proximal humerus: The proximal humerus is moderately enlarged bilaterally. (Also note narrow pulmonary apices, small clavicles with distal resorption, thin ribs with anterior resorption and cardiomegaly.) b: 12 year old boy with Progeria with enlarged proximal and distal humerus: This patient shows mild enlargement of the proximal humerus with comparable enlargement of the distal humerus, particularly laterally. The diaphysis is mildly narrowed. (Also note pseudoarthrosis of the distal clavicle.) c: 4 year old sister of patient in figure 4b who also has Progeria: This image, in comparison to figure 4c, reveals normally sized proximal and distal humerus without diaphyseal narrowing. (Also note mild resorption of the distal clavicle which is mildly narrowed.)

Fig 5

10 year old girl with Progeria with enlarged irregularly shaped greater trochanter: Once the femoral greater trochanter begins to calcify, it often becomes enlarged and elongated superiorly. (Also note small cortical notch defects in both medial femoral necks, left more pronounced than the right (arrows). Also there is mild hip dysplasia, with coxa valga and moderately enlarged proximal femurs (coxa magna).

Fig 6

5 year old girl with Progeria with pseudoarthrosis: There is pseudoarthrosis of the distal left clavicle. Both clavicles are thin with distal resorption.