Paediatric musculoskeletal radiology

The bone dysplasias

 

These are systemic disorders affecting bone and often are associated with dwarfism. Although there is a large number of these, many of them are relatively common. They are much more common than many conditions that are well recognized by radiologists - for example, malignant bone tumors. The prevalence of achondroplasia is 37-64 per million, thanatophoric dysplasia 28-60 per million, achondrogenesis 23-28 per million, osteogenesis imperfecta 36-64 per million, as compared to all malignant tumors in which it is 5.3 per million. The incidence of all the bone dysplasias is 244-322 per million. The radiologic diagnosis of these conditions has real importance since in many of them the radiological diagnosis is the final word. In many of the bone dysplasias there are no other specific biochemical or other tests. Even when such tests are available in some disorders, such as the mucopolysaccharidoses, the radiological appearance points to which test should be done to confirm the diagnosis. The importance of correct diagnosis is also to determine prognosis and genetic counselling. For example, a condition such as achondroplasia usually has a good prognosis so an affected achondroplastic neonate who may have severe respiratory distress should be actively treated. On the other hand, the neonate with thanatophoric dysplasia need not since there is no chance of survival. Also, it is important to know what other associated anomalies may be present. For example, in chondroectodermal dysplasia there may be congenital heart disease and in spondyloepiphyseal dysplasia there may be congenital myopia with retinal detachment.

Prenatal radiologic evaluation of bone dysplasia is usually done with ultrasound. Unfortunately, specific diagnosis is often difficult to determine unless one knows that an affected infant was previously born to the mother. Occasionally, radiography may be of value particularly in evaluation of osteogenesis imperfecta. For such studies it is worthwhile to sedate the infant by giving the mother 10-15 mg of morphine intramuscularly before radiography.

Approach to the bone dysplasias

For optimal evaluation of the bone dysplasias a complete bone survey should be done including the limbs, skull, spine, hands and feet. Although sometimes a diagnosis can be suggested from specific radiographs, the chance for error decreases if the entire skeleton is examined. To be able to diagnose these conditions one needs to know some of the cardinal radiographic signs. The appearance of the diaphysis, the metaphysis, physis and epiphysis are important both in terms of their shape and configuration. The bone length of various bones is also important. Is the shortening rhizomelic (humeri and femora), mesomelic (tibia and fibula or radius and ulna), or acromelic (hands and feet)? The shape, size, and density of the vertebrae are also important. Not all the described findings for a dysplasia may be present in an individual. (A

a	Figure 35. Achondroplasia. a) Pelvis of a 6-month-old achondroplastic infant. Note the square appearing pelvic wings with flat acetabular angles and a sharp sacroscatic notch. This appearance is very characteristic of hondroplasia. b) Normal pelvis. There is a normal lower iliac segment in the pelvis which gives the pelvic wing an appearance of a paddle with a handle. The pelvis in achondroplasia has the appearance of a paddle without a handle since it lacks the lower iliac segment. c) Lack of widening of the distance between the pedicles as one descends in the lumbar spine. This is common in achondroplasia. three legged dog is still a dog!)
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A few of the more common bone dysplasias will be described briefly here. The reader is advised to refer to texts on the subjects for more complete information.

Achondroplasia

This is the most common short limbed bone dysplasia. The affected infants have a depressed nasal bridge and a prominent forehead with somewhat rhizomelic short limbs. The radiographic appearance is often characteristic. The pelvis has square wide iliac wings with flat acetabular angles (Fig. 35 a). The appearance has been likened to that of a paddle without a handle and is due to the lack of the normal lower iliac segment (Fig. 35 b). There is lack of the normal widening of the interpedicular distance as one descends down the lumbar spine (Fig. 35 c). There is also narrowing of the AP diameter of the spine. Clinically, the narrow spinal canal may become significant in adult life when even, small, hypertrophic spurs may impinge upon the spinal cord. Although the cerebral ventricles are often dilated this is usually not a significant hydrocephalus. Achondroplasia is inherited as autosomal dominant. If two achondroplastic parents have a child they have a one in four chance of having one that receives the achondroplastic gene from each of the parents resulting in homozygous achondroplasia which is usually fatal in infancy or early childhood. The radiologic appearance of the homozygous form is much more severe than ordinary (heterozygous) achondroplasia and can be distinguished from it radiologically.

Thanatophoric dysplasia

The term thanatophoric means death-dealing and indeed affected infants are still-born or usually die a few days after birth. Characteristically the infants have a long trunk and very short curved limbs. The most characteristic radiological findings are very flat ossification centers of the vertebral bodies that are most easily recognized in the lateral view(Fig. 36 a). Usually central indentations are present and there are large spaces between the ossified centres. The femora and other bones are very short and usually curved (Fig. 36 b). Although thanatophoric dysplasia was previously confused with achondroplasia it is easily distinguishable. It is a very different entity and it is not related genetically. It is probably inherited as an autosomal dominant.

 

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Figure 36.Thanatophoric dysplasia. a) Lateral view. The vertebrae appear very flat with large spaces between them. Histologically the vertebrae are actually not flat but have very flat ossification centres. The limbs are very short. b) The femora are very short and curved. The pelvis is somewhat similar to that in achondroplasia, but is much more severely involved. The trunk is long.

Achondrogenesis

This other relatively common group of fatal neonatal dysplasias is achondrogenesis. Characteristic of this group is lack of ossification of the vertebral bodies with a relatively short trunk (Fig. 37). There are several forms of achondrogenesis, some with long, and others with short limbs. Most are inherited as autosomal recessive.
There are many other fatal neonatal conditions including several with very short ribs and polydactyly.

 

		Figure 37. Achondrogenesis. Lateral view. The trunk is short and the abdomen is protuberant in contradistinction to the long trunk of thanatophoric dysplasia. There is very poor ossification of the vertebral bodies, but somewhat better ossification of the posterior elements.
		Figure 38. Chondrodysplasia punctata. There are multiple punctate calcifications in the wrist and elbow regions. The skin appears mottled, which is due to the severe ichthyotic changes in the skin.

Chondrodysplasia punctata

This is a heterogeneous group of conditions associated with small punctate calcifications in the epiphyses that are present at birth (Fig. 38). The two major types are the x-linked dominant form (Conradi-Hünerman type) and the rhizomelic form which is inherited as autosomal recessive. The later form is a peroxisomal disorder and is often associated with migrational disorders of the brain. The presence of the puncta in the cartilage is usually associated with abnormality of growth and development. The punctata usually disappear after a few years of life so that in older children the diagnosis can only be made by the presence of resulting deformity which may be non-specific. A close clinical and radiologic mimic of chondrodysplasia punctata is seen in infants of mothers who have received the anticoagulant warfarin. Another mimic is the Zellweger Syndrome (cerebrohepatorenal syndrome) which is another peroxisomal disorder. A distinctive finding of the Zellweger syndrome is the common location of the puncta in the patellae. Punctata may also be seen in a variety of other forms of chondrodysplasia punctata as well as other diseases including trisomy 18 and 21 and fetal alcohol syndrome. In many of these other disorders the puncta involve only the tarsal bones.

Diastrophic dysplasia

This condition is characterized by dwarfism associated with club feet and a normal facial appearance. Sometimes ear swellings are present at birth which results in ear deformity later in life. At birth the knee ossification centres are very retarded. When they ossify they are flattened and irregular. Later in life this results in severe arthritis. The thumb is very short with a short often round first metacarpal (Fig. 39 a). Also peculiar longitudinal epiphyses are often seen in the phalanges of the hand. One of the major complications of diastrophic dysplasia is acute kyphosis in the midcervical spine which may result in cord compression (Fig. 39 b). This dysplasia is inherited as autosomal recessive.

Chondroectodermal dysplasia (Ellis van Creveld syndrome)

This is a dysplasia which is characterized by short limbed dwarfism, polydactyly, and nail and tooth abnormalities. It is inherited as autosomal recessive. Congenital heart disease is present in over half of the cases. A large atrial septal defect or a single atrium is the most common cardiac

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Figure 39. Diastrophic dysplasia. a) Hand in a newborn infant. Note the very short round first metacarpal and a thumb that points away from the hand in a hitch-hiker position. There is also an abnormal proximal phalanx of the middle finger. This is due to an unossified longitudinal epiphysis. The car pal ossification centres are somewhat early which is common in this condition. b) Severe kyphosis in same neonate as in a. This severe angulation is seen in about 15 % of infants with diastrophic dysplasia and it can cause spinal cord compression.

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anomalies. There is postaxial polydactyly of the hand. The distal phalanges of the hand are hypoplastic and there are cone shaped epiphyses in the middle phalanges (Fig. 40). Several carpals are often fused. There may be a hypoplastic thoracic cage.

Asphyxiating thoracic dysplasia - Jeune syndrome

The main manifestation of this condition is a small thorax which results in respiratory distress. The condition may vary from very severe to quite mild. The infants with the mild cases survive but may develop renal failure in later childhood due to microcystic renal disease (nephronopthisis). In the neonate this disorder may be difficult to differentiate from chondroectodermal dysplasia since occasionally polydactyly may be present.

Figure 40. Chondroectodermal dysplasia (Ellis-van Creveld syndrome) in a 6-year-old girl. The tubular bones are short. There is deformity of the fifth metacarpal, and a residual of a sixth finger that was previously present. There is fusion of the capitate and hamate and an additional carpal bone. The distal phalanges are quite characteristic with very unusual long thin epiphyses, particularly in the second and fifth digits. There are also short middle and proximal phalanges with characteristics cone epiphyses.

Spondyloepiphyseal dysplasia congenita

These infants have a flat face and a short trunk. Some have a cleft palate, club feet, and myopia. The most characteristic appearance radiographically is a marked delay in ossification of the pubis, talus, and calcaneus. In the spine there is flattening or hypoplasia of the vertebral bodies.

Hypophosphatasia

This is a condition of variable severity. In the severe infantile form the whole skeleton is very poorly ossified with marked cupping of the ends of the bones with poor ossification of the skull. The cupped ends of the bones can be detected on prenatal ultrasound. In older children spotty lucencies and lucent defects are present in the metaphyses of long bones which sometimes may be confused with rickets (Fig. 41). Serum alkaline phosphatase is very low and there is increased excretion of phosphoethanolamine in the urine.

	Figure 41. Hypophosphatasia. III defined lucencies are seen in the distal femoral and proximal tibial metaphyses. In the distal radius these have a more punched out appearance. Although hypophosphatasia can sometimes be confused with rickets, differentiation usually is not difficult as in rickets the metaphyseal lucency and irregularity is similar across the whole growth plate.
	Figure 42. Metaphyseal chondrodysplasia (Jansen type). Extensive dense calcification is seen in all metaphyseal regions. This appearance is pathognomonic of this rare disorder.

Metaphyseal chondrodysplasias

There are several metaphyseal chondrodysplasias that are characterized by irregularity of the metaphyses with some similarity to rickets. The most characteristic of these is the Jansen form which at birth has the appearance of rickets. In early childhood dense, irregular calcifications occur in the ends of the bones which are pathognomonic of this condition

Figure 43. Metaphyseal chondrodysplasia (McKusick type). There is metaphyseal irregularity with some areas of lucency and sclerosis. This is a disorder often associated with severe immune deficiency.

(Fig. 42). In the adult the bones are short thick with bulbous ends. A recessively inherited form of this disease, the McKusick form, is important to recognize because it is associated with immune defects. Both T cell and B cell defects may occur. The characteristic radiological appearance is of rickets-like changes in the ends of the bones. They differ from rickets in that there are areas of focal sclerosis in the metaphyses (Fig. 43) and that there is shortening of the long bones.

Osteogenesis imperfecta (OI)

This is a group of diseases that were previously clinically divided into four forms. Actually they represent a large number of different abnormalities mostly involving type I collagen. Many different often single amino acid substitutions at various positions in the collagen I chain have been found. The severe neonatal form of OI itself has a wide spectrum; sometimes presenting with marked shortening and widening of the long bones in an accordion pattern (Fig. 44) while in others there are very thin bones which are bowed or broken. At birth fresh fractures may or may not be present but, instead, healing fractures may be evident in the long

Figure 44. Osteagenesis imperfecta type II. Severe neonatal form. This infant had the appearance of a short limb dwarf. There is marked telescoping of bones particularly the femora. Multiple healing fractures are seen. Same bones are bowed.

bones or ribs. Skull ossification is very poor at birth and sometime the skull bones are barely visible. Multiple wormian bones (sutural bones) are commonly seen although they are usually seen better later in childhood. In milder forms of OI the fractures may not occur until the child is several years old. Prognosis in the neonatal form depends on the number of fractures. Blue sclera are seen in many forms. Most of the forms of OI are inherited as autosomal dominant. Sometimes the less severe forms of OI may be mistaken for child abuse. Skull radiographs are of value in such cases since if wormian bones are present the diagnosis of OI is more likely.

Osteopetrosis

This is a condition of increased bone density which has been seen in infants, children, and adults. In infants the bone may be very dens e and the marrow space very small resulting in lack of bone marrow and hence anemia and leucopoenia. In the infant lucent bands may be seen at the metaphyseal ends. Considerable bony sclerosis is also present in older individuals frequently with bands of sclerosis and lucency perpendicular

Figure 45. Multiple exostoses. The exostoses point away from the growth plate. They are seen at most of the bone ends.

to the bony shaft. The bones are often brittle and fractures are not uncommon. There are many other sclerotic bone dysplasias. Another characteristic one is pyknodysostosis in which there is associated acro-osteolysis and hypoplasia of the acromial ends of the clavicles.

Cleidocranial dysplasia

This is a disorder with absence or a hypoplasia of the clavicles, delayed ossification of the pubis and often posterior defects in ossification of the spine. The children who are affected may be able to place their shoulders together anteriorly. In the hand, abnormal, thick epiphyses are seen in the distal phalanges. Inheritance is autosomal dominant.

Multiple hereditary exostoses (MHE)

Exostoses seen in MHE are bony projections covered in childhood by a cartilaginous cap. They are present in the metaphyses of bones and point away from the growth plate (Fig. 45). They can result in growth disturbances if they are close to the growth plate. The disturbances are particularly severe in the ulna where they can cause severe shortening and

 

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Figure 46. Enchondromatosis (Maffucci type). This type is associated with hemangiomas. a) Multiple lucent defects involve many of the bones of both hands. Mostly the diaphyses are affected. On the left there are many areas of widening of the soft tissues. b) Arteriogram of the left hand. There is an extensive increase in vascularity in the region of the soft tissue swellings indicating the presence of hemangiomas.

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deformity of the radius as well. The metacarpals or phalanges may also be affected with resulting shortening or deformity. In the hand the exostoses may be difficult to see since they are small. In the pelvis there is a coxa valga deformity with thick, irregular femoral necks. The exostoses may press on nerves or vessels. Adjacent bones may be deformed by an exostosis in a nearby bone. The incidence of malignancy is now considered to be about l % in this disorder. Multiple hereditary exostosis is inherited as autosomal dominant.

 

Figure 47. Neurofibromatosis with pseudoarthrosis of the tibia and fibula. The defect in the tibia and fibula is one of the manifestation of this disease. It is not due to neurofibromatosis tissue in the gap but is due to mesenchymal abnormality.

Multiple enchondromatosis (Ollier and Maffucci syndrome)

There are two types of this disease; Ollier disease which is the more common type and Maffucci syndrome which is the association of multiple enchondromatosis with hemangiomas (Fig. 46). Although Ollier disease is usually asymmetrical it is rarely unilateral. Growth disturbances may result from enchondromas near a growth plate. There is an increased risk of malignancy present in both forms of the disease. The risk of malignancy, however, is much greater in Maffucci syndrome where not only bone neoplasms occur, but cerebellar, cerebral, and soft tissue malignant vascular tumors may be seen.

Neurofibromatosis (NF)

This is a condition with many different manifestations in the skeleton as well as other parts of the body. There are two forms of the disease (NF1 and NF2) each due to a different gene abnormality. NFI is the one associated with most skeletal anomalies. In the newborn, there may be bowing of the tibia and fibula, sometimes with pseudoarthrosis (Fig. 47).

Figure 48. Larsen Syndrome. This is a syndrome of multiple dislocations and flat face. There is a double ossification of the caccaneus. This is a very rare isolated normal anomaly. When present in association with dislocations, particularly of the knees, it is characteristic of the Larsen Syndrome.

These defects represent mesodermal abnormalities and are not due to local neurofibromas. They are very difficult to treat. There may be localized enlargement of any body part associated with large fusiform neurofibromas in the soft tissues. These are well visualized on MRI and are often associated with thickening of nerves. When the hip is affected there is often a coxa valga deformity, as well as a deformity of the pelvis. In the thoracolumbar spine a sharply angulated scoliosis may be present while in the cervical spine there may be a sharp kyphosis and/or there may be enlargement of the neural foramina. Defects in the occipital part of the skull are occasionally seen. There may be absence of the lesser wing of the sphenoid. These defects are also not due to destruction by neurofibroma but are due to a mesodermal defect. Spinal cord tumors and optic nerve glioma may be seen. The neural changes are best shown with MRI. Abnormal signal abnormalities present in the brain in neurofibromatosis are common but have not been adequately explained. Arterial lesions may also be present with narrowing of the renal or other arteries.

Larsen syndrome

This is a syndrome of multiple dislocations. Additional characteristic radiological findings in the young infant include double ossification of the calcaneus (Fig. 48) and short, broad metacarpals. Sharp kyphosis in the mid cervical spine may be seen. It may compress the cervical cord and cause quadriplegia or death. In older children there may be considerable irregularity in shape and location of the carpals, and there may be multiple extra carpals.

 

Figure 49. Holt Oram Syndrome with triphalangeal thumb, which appears finger-like. This is a syndrome of atrial or ventricular septal defects associated with hand abnormalities ranging from a triphalangeal thumb to an absent thumb.

Holt Oram syndrome

This is a syndrome of atrial or ventricular septal defects, or a conduction defect of the heart associated with a variety of radial abnormalities which range from triphalangeal thumb (Fig. 49) to an absent thumb or phocomelia. The triphalangeal thumb is rarely seen in other conditions and when present with the above heart defects Holt Oram syndrome should be suspected. The condition is inherited as autosomal dominant. It needs to be differentiated from the VATER association (Vertebral anomalies, imperforate Anus, Tracheoesophageal fistula, Esophageal atresia, Radial defect) which is a nongenetic association of anomalies. Many other anomalies can occur with those in the VATER association including heart disease as well as renal and other bone anomalies.

Gaucher disease

This is a disease caused by a deficit of glucocerebroside hydrolase resulting in storage of glucosylceramide within the lysosomal bodies of macrophages and other reticuloendothelial cells. This causes alterations in the bone marrow, enlargement of the spleen, and a modelling abnormality with an Erlenmeyer flask appearance of the lower femora (Fig. 50 a). Aseptic necrosis of the proximal fem oral epiphysis or of the

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Figure 50. Gaucher Disease. a) 8-year-old girl. There is an Erlenmeyer flask deformity of the distal femur. This is a manifestation of Gaucher disease in children. b) Same girl at 6 years of age. There are multiple areas of lucency and sclerosis in the femoral heads, which represent aseptic necrosis. There is also a fracture of the femoral neck with sclerosis around it. This fracture was incidentally discovered and was not clinically suspected. This type of fracture is very characteristic of Gaucher disease.

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femoral neck with sclerosis and sometimes fractures may be seen (Fig. 50 b). The necrosis also often involves the diaphysis. The spleen is markedly enlarged. Vertebra plana may be seen. MRI is of value to determine the extent of the various changes that can occur in the bone marrow of these children before they are apparent on radiography. They may include aseptic necrosis, fresh hemorrhage or infarcts.

The mucopolysaccharidoses (MPS)

These are disorders of mucopolysaccharide metabolism with excretion of mucopolysaccharides in the urine. Although there are at least eight

a	Figure 51. Mucopolysaccharidosis type IH (Hurler disease) a) Characteristic appearance of the pelvis with a pinched in appearance of the lower iliac areas. Compare this to the normal pelvis in Figure 35 b. The acetabula are poorly formed and there is coxa valga deformity. b) There is poor modelling of the metacarpals which appear wide. The proximal ends of the metacarpals are pointed. c) The ribs appear thick, particularly away from the spine while near to the spine they are of normal caliber. d) Minimal anterior beaking of thoracic lumbar vertebrae.
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	Figure 52. Joint effusion demonstrated with ultrasound. On the left there is a large sonolucent space in front of the left femoral neck which represents a hip effusion. White on the right the structures appear normal.

defined clinical types there are many more enzyme abnormalities associated with them. They all have similar radiologic changes but with considerable variation in severity. Some have distinctive changes of their own. The most common finding to all is in the pelvis with thinning of the lower iliac segment (Fig. 51 a). Other findings include relatively thick coarse bones and some pointing at the proximal ends of the metacarpals (Fig. 51 b). The ribs are often wide away from the spine and relatively thin near it (Fig. 51 c). The classic MPS changes are seen in the Hurler form (MPS IH) (Fig. 51). In other forms they may be milder such as in the San Filippo form (MPS III). In MPS IV (Morquio syndrome) flat vertebral bodies are seen throughout the spine while in the other forms of MPS only beaking in the thoracolumbar region may be seen (Fig. 51 d). Clinical and radiologic diagnosis to determine the specific type is useful as it decreases the number of tests that need be done to characterize the disorder.

 

Andrew K. Poznanski