Each limb consists of four segments, including a root or zonoskeleton; a proximal segment or stylopodi- um, consisting of a single bone (humerus, femur); a medial segment or zeugopodium, consisting of two bones (radius and ulna; tibia and fibula); and a distal part or autopodium, corresponding to hand and foot.
The complex processes involved in the formation of these segments and pertinent genetic hints have been reviewed in Chapter 6.
Development of the bones in the limbs takes place for the most part by virtue of endochondral bone formation, that is, transformation of the primitive mesenchyma into an intermediate cartilage model, which subsequently ossifies. First, a network of immature, woven-fibered trabeculae (the primary spongiosa) is produced. Later, the primary spongiosa is replaced by secondary bone, which is either trabec- ular or cortical, depending on the location (Frost 1983). Ossification starts at approximately the mid- point of the cartilaginous model (primary ossifica- tion center) and proceeds toward both ends of the bone until a plate of cellular activity is created at the interface between the diaphysis and the epiphysis.
This growth plate, or physis, allows for longitudinal growth of the bone until its final length is achieved.
The primary ossification centers for the femur make their appearance around the 7th week of gestation, while those for the humerus, radius, ulna, tibia, and fibula appear around the 8th week of gestation. As endochondral ossification proceeds, the mesenchy- mal cells surrounding the cartilaginous model un- dergo transformation into osteoblasts (intramem- branous bone formation) and lay down bone in the subperiosteal zone, which is destined to form the cortex of the developing bone. By ossification of the secondary centers within the epiphyses at the ends of the bone, the epiphyseal cartilage is converted to bone, except for a thin peripheral layer, which per- sists as articular cartilage of the intervening joint.
The tubular bones with secondary ossification cen- ters at both ends are termed, by convention, ‘long’
bones, while those with a center at only one end are termed ‘short’ bones. The secondary ossification cen-
ters for the head of the humerus, distal femur, and proximal tibia make their appearance around the 36th week of gestation, while those for the femoral head and capitulum of humerus do not appear until the 2nd to the 6th month after birth. The distal epi- physis of radius usually appears around 12 months, and the greater trochanter of femur and proximal epiphysis of fibula at about 3 years of age. Ossifica- tion of the long bones extends a long way into child- hood and early adolescence, with the patella develop- ing at about 4 years, the capitulum of the radius at 5 years, the medial epicondyle of the humerus at 6 years, the distal epiphysis of the ulna at 7 years, the olecranon of the ulna at 10 years, and the lateral epi- condyle of the humerus and tubercle of the tibia at 11 years (Garn et al. 1967). With further growth, the physeal plate becomes progressively narrowed and finally disappears, allowing fusion between the epi- physis and the diaphysis.
At any stage of development, even when growth is
complete, the normal bone is an active, dynamic tis-
sue in which the process of bone formation is bal-
anced by that of bone resorption. This balance is ac-
complished by the integrated activity of specialized
bone cells, i.e., osteoblasts and osteoclasts, which are
enrolled into the process of growth, fracture healing,
modeling, and remodeling of the living human
skeleton (Resnick et al. 1995). Modeling is the dy-
namic process by which major adjustments in the
size and shape of the bones are produced. The
process of modeling, which depends heavily upon
the mechanical forces applied to the skeleton,
is most prominent in the immature skeleton until
adolescence, and results in a net increase in the
amount of bone tissue, especially in the sub-
periosteal location. Remarkable examples of bone
modeling in the tubular bones include: (a) drifting
of the midshaft, accomplished by endosteal bone
resorption and periosteal bone formation; and (b)
flaring of the metaphyses, accomplished by re-
sorption along the periosteal surface and apposi-
tion in the endosteal surface. In this way the wide
metaphysis is substituted by a narrow diaphysis
Alessandro Castriota-Scanderbeg, M.D.
as the bone grows in length. Remodeling is the dy- namic process that modifies bone quality, causing the structurally inferior woven-fibered bone of the infant to give way to the more compact lamellar bone of the adult (Resnick et al. 1995). In addition, remodeling replaces aged or injured bone tissue with new bone, a process requiring a tight balance between resorption and formation of the cortical and trabecular bone.
References
Frost HM. The skeletal intermediary organization. Metab Bone Dis Relat Res 1983; 4: 281–90
Garn SM, Rohmann CG, Silverman FN. Radiographic stan- dards for postnatal ossification and tooth calcification. Med Radiogr Photogr 1967; 43: 45–66
Resnick D, Manolagas SC, Niwayama G, Fallon MD. Histogene- sis, anatomy, and physiology of bone. In: Resnick D (ed.) Diagnosis of bone and joint disorders.W. B. Saunders Com- pany, Philadelphia, 1995 (3rd ed.), pp. 609–51
Abnormalities of the Shape and Contour of the Long Bones
The delicate balance of bone resorption and bone formation, as outlined above, can be altered by a number of factors, including congenital and acquired diseases and drugs, notably diphosphonates (Miller and Jee 1979). As stated earlier, the modeling process produces major changes in the shape and size of the bones (Silverman 1990). Defective modeling of the tubular bones can result in either increased or reduced tubulation. Overtubulation, a condition of diminished periosteal deposition, gives rise to long, slim bones, whereas undertubulation is associated with bone shortening and either diaphyseal or meta- physeal expansion. Pathologic conditions involving undertubulation include most skeletal dysplasias characterized by increased bone density, e.g., osteo- petrosis and both craniometaphyseal and craniodia- physeal dysplasias. In addition to modeling defects, many other factors can lead to major changes in the shape and contour of the long bones: defective endo- chondral bone formation within the physis (e.g., achondroplasia, especially the homozygous form), bone marrow infiltration and expansion (e.g., ane- mias and storage diseases), muscle inactivity and dis- use (e.g., neuromuscular disorders), inherent bone weakening (e.g., osteomalacia), and several others. In most cases, the final shape of the bone is the result of a complex interaction between different and some- times unrelated factors.
Some important alterations in the shape and con- tour of the tubular bones are emphasized in this chapter, and the principal mechanisms of their de- velopment are discussed. The coexistence of different
‘shapes’ in a single bone (e.g., the long bones in os- teopetrosis are bowed and widened, in addition to being dense) precludes firm categorization of indi- vidual disorders in one section or another, a circum- stance that is reflected in the large overlap within and across sections in the chapter.
References
Miller SC, Jee WS. The effect of dichloromethylene diphospho- nate, a pyrophosphate analog, on bone and bone cell struc- ture in the growing rat. Anat Rec 1979; 193: 439–62 Silverman FN. The bones: normal and variants. In: Silverman
FN, Kuhn JP (eds.) Caffey’s pediatric X-ray diagnosis. Year Book Medical Publisher, Inc., Chicago, 1990, pp. 1465–527
Broad Tubular Bones
䉴 [Expanded tubular bones]
Several mechanisms can account for broadening of the tubular bones, including defective modeling, cor- tical hyperostosis, bone marrow hyperplasia or infil- tration, and new bone deposition in the periosteum and adjacent soft tissues. As a consequence, broad tubular bones are seen in a wide variety of disorders, both congenital and acquired, including several skeletal dysplasias, metabolic disorders, and hemato- logical diseases. Depending on the underlying etiolo- gy, broadening of the long bones is focal or general- ized, symmetrical or asymmetrical. This section of- fers an overview of the conditions characterized by defective modeling and bone marrow infiltration/
hyperplasia. The subject of cortical hyperostosis is addressed in the section of this chapter headed “Cor- tical Thickening.”
Failure of normal modeling of a tubular bone (un- dertubulation) can cause either diaphyseal or meta- physeal expansion, or both. Diaphyseal expansion is typically seen in patients with diaphyseal dysplasia (Camurati-Engelmann disease, OMIM 131300; Fig.
5.1), in which the tubular bones manifest enlarged
and sclerotic diaphyses, cortical thickening, and nar-
rowing of the medullary cavity (Crisp and Brenton
1982; Neveh et al. 1984). Undermodeled tubular
bones with expanded diaphyses and thin cortices are
seen in craniodiaphyseal dysplasia (OMIM 122860,
218300), a disorder with severe sclerosis and hyper-
ostosis of the facial and skull bones (leontiasis ossea). A severe modeling defect resulting in club- shaped metaphyseal expansion with cortical thin- ning, which is most prominent in the distal fe- murs, occurs in craniometaphyseal dysplasia (OMIM 123000, 218400). Metaphyseal widening does not be- come apparent until childhood, while in infancy the disease manifests with diaphyseal sclerosis and nor- mal metaphyses, thereby simulating diaphyseal dys- plasia (McAlister and Herman 1995). Extensive scle- rosis of the skull base and facial bones, with oblitera- tion of the paranasal cavities, is characteristic of this condition but is less prominent than in craniodia- physeal dysplasia. In frontometaphyseal dysplasia (OMIM 305620), changes in the long bones, including metaphyseal widening and thin cortices, are similar to, but milder than, those of craniometaphyseal dys- plasia. The differential diagnosis is based on the appearance of the facial bones (unaffected in fron- tometaphyseal dysplasia and diffusely sclerotic in craniometaphyseal dysplasia) and pelvis (marked flaring of iliac wings in frontometaphyseal dysplasia and normal appearance in craniometaphyseal dys- plasia). In metaphyseal dysplasia (Pyle disease,
OMIM 265900) the extreme expansion of the meta- physis, extending well into the diaphysis, leads to the characteristic Erlenmeyer flask deformity in the femur and tibia. Pyle disease resembles craniometa- physeal dysplasia in most respects. Distinctive fea- tures in Pyle disease include milder sclerosis of the skull bones, with no symptoms of cranial nerve com- pression, and a more severe tubulation defect about the metaphyses. Furthermore, the inheritance pat- tern is autosomal recessive in Pyle disease, and auto- somal dominant in craniometaphyseal dysplasia. In the autosomal recessive hereditary hyperphosphata- sia (juvenile Paget disease, OMIM 239000) the tubu- lar bones are markedly widened and bowed, with thick or thin cortices and subsequent narrowing or widening of the medullary cavity, which can hardly ever be distinguished from the cortex. In oculo-den- to-osseous dysplasia (OMIM 257850) failure of nor- mal tubulation results in mild to moderate widening of the tubular bones, involving either the metaphysis or the entire shaft. In osteopetrosis, precocious type (OMIM 259700) the homogeneously dense long bones display undermodeled, club-shaped metaphy- ses. Osteopetrosis, delayed type (OMIM 166600) is also characterized by varying degrees of impaired bone modeling.
Enlargement of the tubular bones as a result of bone marrow infiltration is usually associated with cortical erosion and thinning. In lipid storage dis- eases, including Gaucher’s disease (OMIM 230800) and Niemann-Pick disease (OMIM 257250), widening of the medullary cavity with cortical diminution is secondary to marrow infiltration by lipid-containing cells (Matsubara et al. 1982). In both diseases model- ing deformities also occur, especially at the distal ends of the femoral shafts, resulting in the Erlen- meyer flask deformity (Resnick 1995; Lachman et al.
1973). In mucopolysaccharidosis I-H (Hurler disease, OMIM 252800), the changes in the long tubular bones, which are most prominent at the upper extremities, include diaphyseal and metaphyseal ex- pansion, cortical thinning, and delayed epiphyseal ossification. In mucopolysaccharidosis VI (Maroteaux- Lamy syndrome, OMIM 253200) the tubular bones are relatively short and show irregular diaphyseal widening and submetaphyseal overconstriction. A few patients with childhood lymphoproliferative dis- orders, including leukemia, lymphoma, and masto- cytosis, manifest bony enlargement. More typical manifestations in these disorders are bone destruc- tion with periostitis and osteosclerosis, either focal or diffuse. Conditions involving severe and long- standing anemia, such as thalassemia major, may
Fig. 5.1. Diaphyseal dysplasia (Camurati-Engelmann disease)
in a 36-year-old woman. Note fusiform thickening of the cor-
tex in the diaphyseal portion of the femur (site of intramem-
branous ossification). Cortical thickening is due to periosteal
and endosteal bone apposition. The external contour of the
bone is regular. The medullary cavity is narrowed. (From Van-
hoenacker et al. 2000)
result in alteration of the long bone contour, with metaphyseal and epiphyseal widening, cortical thin- ning, and a coarse, trabeculated appearance. These alterations, which are due to reactive bone marrow hyperplasia, are now prevented in developed coun- tries by maintaining appropriate levels of serum hemoglobin with transfusions.
Two major mechanisms are believed to cause broadening of the long bones in neurofibromatosis type 1 (OMIM 162220): (a) a modeling defect, result- ing in metaphyseal expansion; and (b) periosteal overgrowth secondary to subperiosteal hemorrhage and/or soft tissue infiltration by neurofibromas, which are subsequently incorporated into the cortex.
In hemophilia (OMIM 306700), extensive subpe- riosteal bleeding may eventually calcify over time (Swischuk and John 1995, p. 198). New bone deposi- tion at or around the periosteum can manifest as overall ballooning of the parent bone. In Caffey disease (OMIM 114000) bone deposition occurs within the soft tissues surrounding the periosteum.
Subsequent fusion of the new bone tissue with the cortex gives rise to broadening of the involved tubu- lar bone.
Radiographic Synopsis
AP, lateral, and oblique projections. The corticodia- physeal ratio, measured at the mid-shaft of the tibia on AP projection, is increased in conditions with cor- tical thickening and decreased in conditions with medullary expansion and cortical thinning. The ratio is calculated by summing the widths of both cortices and dividing the result by the entire width of the dia- physis. The normal corticodiaphyseal ratio in chil- dren over 18 months of age and adults is 0.48±0.09 (Bernard and Laval-Jeantet 1962).
1. Diaphyseal expansion; thick cortices; narrow medullary cavity (diaphyseal dysplasia)
2. Diaphyseal expansion; thin cortices (craniodia- physeal dysplasia)
3. Metaphyseal expansion; thin cortices; club- shaped distal femurs (Pyle disease; craniometa- physeal dysplasia; frontometaphyseal dysplasia) 4. Widening of the medullary cavity; cortical
diminution (storage diseases; lymphoproliferative disorders; severe anemia)
5. Metaphyseal expansion; periosteal thickening (neurofibromatosis type 1)
6. Periosteal thickening (hemophilia; Caffey disease)
Associations
• Achondrogenesis type 1
• Achondrogenesis type 2
• Anemia, severe
• Bleeding (hemophilia, trauma, battered child syndrome, neurogenic fracture)
• Chromosome 8 trisomy syndrome
• Cleidocranial dysplasia
• Craniodiaphyseal dysplasia
• Craniometaphyseal dysplasia
• Craniometadiaphyseal dysplasia, wormian bone type
• Diaphyseal dysplasia (Camurati-Engelmann)
• Diaphyseal dysplasia – anemia
• Diaphyseal dysplasia – proximal myopathy
• Dysosteosclerosis
• Dyssegmental dysplasia
• Endosteal hyperostosis (van Buchem, Worth)
• Exostoses, multiple heritable
• Fibrogenesis imperfecta ossium
• Fibrous dysplasia
• Gaucher disease
• GM1 gangliosidosis
• Hyperphosphatasia, hereditary
• Hypochondrogenesis
• Infantile multisystem inflammatory disease
• Kyphomelic dysplasia
• Mastocytosis
• McCune-Albright syndrome
• Mesomelic dysplasia (Langer)
• Metaphyseal dysplasia (Pyle disease)
• Mucolipidoses
• Mucopolysaccharidoses
• Neu-Laxova syndrome
• Neurofibromatosis
• Niemann-Pick disease
• Oculo-dento-osseous dysplasia
• Opsismodysplasia
• Osteogenesis imperfecta, type II
• Osteopetrosis
• Oto-palato-digital syndrome, type I
• Pachydermoperiostosis
• Pleonosteosis
• Schwarz-Lelek syndrome
• Scurvy
• Singleton-Merten syndrome
• Thanatophoric dysplasia
• Weissenbacher-Zweymuller syndrome
References
Bernard J, Laval-Jeantet M. Le rapport cortico-diaphysaire tib- ial pendant la croissance. Arch Fr Pediatr 1962; 19: 805–17 Crisp AJ, Brenton DP. Engelmann’s disease of bone. A systemic
disorder? Ann Rheum Dis 1982; 41: 183–8
Lachman R, Crocker A, Schulman J, Strand R. Radiological findings in Niemann-Pick disease. Radiology 1973; 108:
659–64
Matsubara T, Yoshiya S, Maeda M, Shiba R, Hirohata K. Histo- logic and histochemical investigation of Gaucher cells. Clin Orthop 1982; 166: 233–42
McAlister WH, Herman TE. Osteochondrodysplasias, dysos- toses, chromosomal aberrations, mucopolysaccharidoses, and mucolipidoses. In: Resnick D (ed.) Diagnosis of bone and joint disorders. W. B. Saunders Company, Philadelphia, 1995 (3rd ed.), pp. 4163–244
Naveh Y, Kaftori JK,Alon U, Ben-David J, Berant M. Progressive diaphyseal dysplasia: genetics and clinical and radiologic manifestations. Pediatrics 1984; 74: 399–405
Resnick D. Lipidoses, histiocytoses, and hyperlipoproteine- mias. In: Resnick D (ed.) Diagnosis of bone and joint disor- ders. W. B. Saunders Company, Philadelphia, 1995 (3rd ed.), pp. 2190–246
Swischuk LE, John SD. Differential diagnosis in pediatric radi- ology. Williams & Wilkins, Baltimore, 1995
Vanhoenacker FM, De Beuckeleer LH,Van Hul W, Balemans W, Tan GJ, Hill SC, De Schepper AM. Sclerosing bone dys- plasias: genetic and radioclinical features. Eur Radiol 2000;
10: 1423–33
Slender Tubular Bones
䉴 [Slim, elongated bones]
Activity is essential to the normal growth and devel- opment of bones. Inactivity from any cause, includ- ing neuromuscular disorders and prolonged immobi- lization or disuse, produces osseous, articular, and soft tissue changes. Osteoporosis, growth distur- bances and deformities, fractures, soft tissue atrophy or – less frequently – hypertrophy, heterotopic ossifi- cation, cartilage atrophy, and synovitis are examples of pathophysiologic responses to the altered equilib- rium between muscle activity and normal growth and integrity of the adjacent bones. The occurrence of one or another of the changes mentioned is relat- ed to the nature of the underlying disorder and to the patient’s age. Osteoporosis accompanying prolonged immobilization, disuse, or paralysis can be focal or generalized, depending on the causative factor. Al- though its pathogenesis is uncertain, a vascular mechanism, with intraosseous venous stasis and stimulation of osteoclastic activity, is likely (van Ouwenaller et al. 1989). Changes in calcium home- ostasis include hypercalcemia, hypercalciuria, hyper-
phosphoremia, and reduced levels of plasma 1,25-di- hydroxyvitamin D, a pattern indicating suppression of the parathyroid-1,25-dihydroxyvitamin D axis (Stewart et al. 1982). Thinning of the long bones may result from active bone resorption either at the level of one of the three cortical envelopes (subperiosteal, intracortical, and endosteal) or at the trabecular lev- el. If the causative mechanism has been exerting its effect since infancy, underdevelopment of the entire affected skeletal area can occur. In these cases, the long bones are gracile, with thin cortices and diaphy- seal constriction. In addition to slender and hy- poplastic long bones, patients with poliomyelitis sometimes experience premature closure of the growth plates and epiphyses about the ankle and knee, with a ‘ball-in-socket’ epiphyseal appearance and pes cavus deformity (Richardson et al. 1984).
Long-standing muscle hypotonia and flaccidity give rise in the immature skeleton to slim bones, coxa val- ga deformity, increased height of the vertebral bod- ies, and narrowing of the intervertebral disks (Hsu 1982). Children with cerebral palsy and muscle spasticity can manifest flexion contracture of the hips, hip dislocation, equinus deformity of the ankle, scoliosis, lordosis, and pelvic obliquity (Mayfield et al. 1981). Children with Erb-Duchenne paraly- sis (damage to the 5th and 6th cervical roots) or Klumpke’s paralysis (damage to the 7th and 8th cer- vical roots) who do not recover over time may dis- play hypoplasia of the involved arm, slender bones, and a variety of shoulder deformities, including hy- poplasia and elevation of the scapula, shallow gle- noid fossa, and tilted coracoid process (Pollock and Reed 1989).
Thin, gracile bones occur in osteogenesis imperfec- ta type I (OMIM 166200) and type IV (OMIM 166220) and in the rare lethal skeletal dysplasia with gracile bones (OMIM 602361), a short-limbed dwarfing con- dition with markedly thin diaphyses, diaphyseal frac- tures, thin ribs and clavicles, facial anomalies, and positional abnormalities of hands and feet (Maro- teaux et al. 1988).
Several connective tissue disorders feature slender limbs. In these cases, muscular atrophy and weakness act in concert with the inherent bone defect in deter- mining bone gracility and slenderness. Marfan syn- drome (OMIM 154700) is an autosomal dominant disorder of the connective tissue primarily involving the eyes, the skeleton, and the cardiovascular system.
Affected patients are typically tall, with long slim limbs, thin subcutaneous fat, and muscle hypotonia.
Arachnodactyly with hyperextensibility is typical
(Magid et al. 1990). Radiographic changes of Marfan
syndrome are similar to those occurring in other con- ditions with ‘marfanoid’ skeletal abnormalities. For example, homocystinuria (OMIM 236200), an autoso- mal recessive disorder with an inborn defect of me- thionine metabolism and excessive plasma levels of homocysteine, shows long slim limbs (dolichoste- nomelia), arachnodactyly, and a constellation of vas- cular, brain, ocular and skeletal derangements, in- cluding vascular narrowing or dilatation, atheroma- tous lesions, ocular lens subluxation, cutaneous malar flush, microcephaly, dural calcifications, enlarged paranasal sinuses, widening of the diploic space of the skull, prognathism, scoliosis, compression frac- tures of the spine with ‘codfish’ vertebrae, sternal de- formities, large metaphyses and epiphyses, and liga- mentous laxity (Brenton 1977). The presence of osteo- porosis, mental retardation, and vascular complica- tions allows differential diagnosis from Marfan syn- drome (Smith 1967). Slender tubular bones are also seen in congenital contractural arachnodactyly (Beals syndrome, OMIM 121050), another inherited disor- der of the connective tissue manifesting with joint contractures (knees, elbows, hips), arachnodactyly,
progressive kyphoscoliosis, and abnormally shaped,
‘crumpled’ ears (Beals and Hecht 1971; Hecht and Beals 1972; Epstein et al. 1968; McKusick 1975) (Fig. 5.2). Beals syndrome differs from Marfan syn- drome in the absence of ocular abnormalities, while cardiovascular abnormalities such as mitral valve prolapse are occasionally found. Patients with Stickler syndrome (arthro-ophthalmopathy, OMIM 108300), a connective tissue disorder with an autosomal domi- nant mode of inheritance, also have a marfanoid habitus, with distinct orofacial changes, including cleft palate and micrognathia (Opitz et al. 1972).
Other disorders with slim long bones are those involving an appearance suggestive of advanced age, including Cockayne syndrome, progeria, and Werner syndrome. Patients with Cockayne syndrome (OMIM 216400) show profound postnatal growth deficiency, early-onset (1st year of life) senile-type changes, mental retardation, central and peripheral nervous system abnormalities, ocular abnormalities, photosensitive skin, a characteristic facies, and slim long limbs (Riggs and Seiberg 1972). Cockayne syn- drome is similar in various features to progeria (OMIM 176670), a probably autosomal dominant disorder with a precocious senile appearance that is striking in degree, thin calvarium with open fontanels, alopecia, thin skin, atrophy of subcuta- neous fat, deficient growth beginning during the first months of life, early-onset atherosclerosis, osteo- porosis, facial hypoplasia, receding chin, beaked nose, and slender tubular bones and ribs (DeBusk 1972; Gillar et al. 1991). Mental development is nor- mal, and acro-osteolysis of distal phalanges and clav- icles are features peculiar to progeria (Reichel et al.
1971). In Werner syndrome (OMIM 277700), an auto- somal recessive disorder (gene WNR mapped to 8p12 is similar to DNA helices), senile-type changes are usually not apparent until early adult life. This syn- drome features absence of the pubertal growth spurt, short stature, skin atrophy with thick fibrous subcu- taneous tissue, gray sparse hair, premature loss of teeth, cataract, slim extremities, small hands and feet, narrow face with beaked nose, atherosclerosis, het- erotopic calcifications, osteoporosis, and an elevated risk of malignancy (Fleischmajer and Nedwich 1973;
Adoue 1997). Thin, gracile tubular bones and ribs are characteristic radiographic manifestations of Haller- mann-Streiff syndrome (OMIM 234100), a sporadic disorder with proportionately small stature, cranio- facial abnormalities (brachycephaly with frontal bossing, malar and mandibular hypoplasia, small pointed nose, narrow palate, dental defects, skin atro- phy, thin sparse hair), ocular abnormalities (mi-
Fig. 5.2. Congenital contractural arachnodactyly in a 13-year-
old girl. Note slim, elongated long bones in the shank
crophthalmia, cataract, strabismus), and skeletal ab- normalities (slender bones, wormian bones, de- creased number of sternal ossification centers) (Stone 1975; Cohen 1991; Scheuerle 1999). The auto- somal recessive 3 M syndrome (OMIM 273750) is characterized by proportionate dwarfism, face with frontal bossing, flattened malar region, short nose with upturned nares, long philtrum, prominent mouth with thick lips, and slender tubular bones and ribs (Feldmann et al. 1989). Slim, stick-like tubular bones are also found in the Pena-Shokeir phenotype (fetal akinesia/hypokinesia sequence, OMIM 208150), a lethal disorder characterized by multiple joint ankylosis, facial anomalies, and pulmonary hypopla- sia (Hall 1986). The designation arthrogryposis is currently applied to the clinical picture of multiple, nonprogressive joint contractures of prenatal onset.
A number of underlying disorders manifest with multiple congenital contractures. Both active and passive motion are limited, the bones are gracile, and the soft tissues are hypotrophic. Equinovarus of
the foot, ulnar deviation of the hand, coalition in the carpus and tarsus, dislocation of hip and patella, fibular hypoplasia, and scoliosis are common fea- tures (Poznanski and La Rowe 1970). In the rare auto- somal recessive Marinesco-Sjögren syndrome (OMIM 248800) the principal features include cerebellar atax- ia, congenital cataracts, mental and physical retarda- tion, myopathy and skeletal anomalies, including kyphoscoliosis, clubfoot, gracile bones, cubitus val- gus, short metatarsals and metacarpals, coxa valga, and microcephaly (Brogdon et al. 1996) (Fig. 5.3a,b).
Radiographic Synopsis
1. Thin, vertically oriented femoral neck (coxa val- ga); underdeveloped, slender tubular bones; os- teoporosis; fractures; soft tissue atrophy; soft tis- sue and bone infections; heterotopic ossification;
cartilage atrophy (neuromuscular disorders, im- mobilization)
2. Thin, gracile bones; multiple fractures (osteogene- sis imperfecta, ‘lethal skeletal dysplasia with gracile bones’)
3. Dolichostenomelia; arachnodactyly (Marfan syn- drome, homocystinuria, congenital contractural arachnodactyly)
4. Slender tubular bones; bulky metaphyses and epi- physes; curved fibulas (Cockayne syndrome) 5. Slim tubular bones (progeria, Werner syndrome,
Hallermann-Streiff syndrome, 3M syndrome, Mari- nesco-Sjögren syndrome)
6. Gracile bones with slim tubular bones; multiple joint contractures (Pena-Shokeir phenotype, arthro- gryposis)
Associations
• Arthrogryposis
• Caudal dysplasia sequence
• Cockayne syndrome
• Congenital contractural arachnodactyly (Beals syndrome)
• Hallermann-Streiff syndrome
• Homocystinuria
• Hypopituitarism
• Intrauterine dwarfism, peculiar facies and thin bones with multiple fractures
• Lethal skeletal dysplasia with gracile bones
• 3M syndrome
• Marfan syndrome
• Marinesco-Sjögren syndrome
• Marshall-Smith syndrome
• Muscular dystrophies
• Neurofibromatosis
• Neuromuscular disorders
Fig. 5.3 a, b. Marinesco-Sjögren syndrome. Note slenderness of the long bones in the a lower and b upper extremities. Cubi- tus valgus, and short metacarpals are also apparent in b. (From Brogdon et al. 1996)
a b
• Osteogenesis imperfecta types I, IV
• Pena-Shokeir phenotype
• Progeria
• Pterygium syndrome (lethal multiple pterygium)
• Winchester syndrome
References
Adoue DP. Images in clinical medicine. Werner’s syndrome.
N Engl J Med 1997; 337: 977
Beals RK, Hecht F. Congenital contractural arachnodactyly: a heritable disorder of connective tissue. J Bone Joint Surg Am 1971; 53: 987–93
Brenton DP. Skeletal abnormalities in homocystinuria. Post- grad Med J 1977; 53: 488–96
Brogdon BG, Snow RD, Williams JP. Skeletal findings in Mari- nesco-Sjogren syndrome. Skeletal Radiol 1996; 25: 461–5 Cohen MM Jr. Hallermann-Streiff syndrome: a review. Am J
Med Genet 1991; 41: 488–99
DeBusk FL. The Hutchinson-Gilford progeria syndrome.
J Pediatr 1972; 80: 697–724
Epstein CJ, Graham CB, Hodgkin WE, Hecht F, Motulsky AG.
Hereditary dysplasia of bone with kyphoscoliosis, contrac- tures, and abnormally shaped ears. J Pediatr 1968; 73:
379–86
Feldmann M, Gilgenkrantz S, Parisot S, Zarini G, Marchal C.
3 M dwarfism: a study of two further sibs. J Med Genet 1989; 26: 583–5
Fleischmajer R, Nedwich A. Werner’s syndrome. Am J Med 1973; 54: 111–8
Gillar PJ, Kaye CI, McCourt JW. Progressive early dermato- logic changes in Hutchinson-Gilford progeria syndrome.
Pediatr Dermatol 1991; 8: 199–206
Hall JG. Analysis of Pena Shokeir phenotype. Am J Med Genet 1986; 25: 99–117
Hecht F, Beals RK. ‘New’ syndrome of congenital contractural arachnodactyly originally described by Marfan in 1896.
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Bowed Tubular Bones
䉴 [Curved bones]
Bowing of the long bones can be focal or generalized, depending on whether the causative mechanism acts locally (trauma, infection) or diffusely (skeletal dysplasias, metabolic disorders, malformation syn- dromes). Although traumas in children mostly cause plastic bending fractures, injuries to the epiphysis occasionally lead to more permanent focal bowing by interfering with the normal bone growth.
Long bones whose structure is inherently weak for any reason are prone to bending changes, especially when exposed to the effects of postural influences and weight-bearing. One typical such situation is offered by rickets and osteomalacia, two terms de- scribing gross histopathologic and radiologic abnor- malities that are common to more than 50 diseases varying in cause and clinical presentation (Pitt 1981).
The term ‘rickets’ means a breakdown in the orderly development and mineralization of the growth plate, with deficient mineralization of the zone of provi- sional calcification. ‘Osteomalacia’ means inadequate or delayed calcium hydroxyapatite deposition on bone matrix, with a relative excess of osteoid accu- mulation in mature cortical and spongy bone (Mankin 1974). Therefore, before fusion of the growth plates rickets and osteomalacia can coexist.
Their coexistence facilitates the radiographic diag-
nosis, which is difficult in the presence of osteomala-
cia alone. Children with rickets show characteristic
changes at the growth plates, notably at the costo-
chondral junctions of the middle ribs, the distal ends
of the femur, radius, and ulna, the proximal end of
the humerus, and both ends of the tibia. Features in- clude growth plate widening, decreased density, and irregularities in the zone of provisional calcification, metaphyseal cupping and fraying, increased epi- metaphyseal distance, and bone rarefaction, which is most prominent in the metaphyses (Fig. 5.4a–c).Var- ious bone deformities can develop, depending on the child’s age at disease onset and the duration of dis- ease. In early infancy, changes in the skull are strik- ing, with occipital flattening (caused by supine pos- tural influences) and prominent frontal and parietal bones (caused by accumulation of osteoid). During infancy and early childhood, characteristic bowing deformities of the long bones in the arms and legs become apparent, which are secondary to abnormal postures assumed by the child and/or to displace- ment of the growth centers by unequal musculo- tendinous pulls. With the effects of weight-bearing, bowing deformities in the lower legs tend to worsen, and progressive scoliosis may develop. As mentioned above, when rachitic changes are lacking the radi- ographic recognition of osteomalacia can be ex-
tremely difficult. In fact, osteopenia, a cardinal fea- ture of osteomalacia, is not specific. Cortical hyper- ostosis resulting from (partial) mineralization of ex- cessive subperiosteal osteoid deposition can be diagnostically misleading. Difficulties in diagnosis can also arise from the superimposition of hyper- parathyroidism and osteitis fibrosa cystica, a compli- cation of long-standing low serum calcium levels (Renton 1998). More specific signs of osteomalacia are so-called Looser’s zones, or milkman’s pseudo- fractures. They are seen as focal areas of radiolucen- cy reflecting unmineralized osteoid, which are ori- ented at right angles to the cortex and incompletely span the diameter of the bone (Sabean 1966; Meema and Meema 1975). Their bilateral and symmetrical distribution, and their occurrence at specific sites (ribs, pubis, inner borders of scapula and femur, pos- terior margin of ulna) are characteristic, and allow radiographic differentiation from other disorders with similar findings, such as Paget disease and fi- brous dysplasia. Many rachitic and osteomalacic syn- dromes are caused by vitamin D deficiency (dietary
Fig. 5.4 a–c. Rickets. a In a 2-month-old boy dur- ing the early phase of treatment the distal ends of the radius and ulna are irregularly mineralized, frayed, and cupped. Both bones are undermineral- ized, with a coarse trabecular pattern. The provi- sional zones of calcification are partially recalci- fied and appear as a transverse line of increased density located well beyond the ends of the shafts.
b, c. In a 13-month- old girl 1 month after the be- ginning of treatment the metaphyses are cupped, with a marginal band of increased density due to recalcification of the provisional zone. Note bowing deformity of the ulna (arrows), tibias and fibulas
a b
c
deficiency, gastrointestinal malabsorption, prematu- rity, liver disease, anticonvulsive therapy, renal os- teodystrophy, parathyroid disorders) or by primary renal tubular loss of phosphate (X-linked hypophos- phatemia, disorders of renal tubular dysfunction subsumed under ‘Fanconi syndromes,’ neoplasms, ingestion of such drugs as ipofosfamide) (Pitt 1991).
However, other rachitic and osteomalacic syndromes, such as axial osteomalacia, hypophosphatasia, and metaphyseal chondrodysplasia, are known, in which no detectable vitamin D, calcium and phosphorus metabolism abnormality can be found (Pitt 1995).
X-Linked hypophosphatemia (OMIM 307800), the most common form of renal tubular rickets and osteomalacia, is inherited as an X-linked dominant trait commonly resulting from a de novo mutation
Fig. 5.5. X-linked hypophosphatemia in a 77-year-old woman.
Pronounced femoral bowing is associated with an active mid- diaphyseal lateral Looser zone (arrow) and proliferative changes along the linea aspera (arrowheads). (Reprinted, with permission, from Hardy et al. 1989)
Fig. 5.6 a–c. Hypophosphatasia, congenital lethal form. a Fe- male fetus of unspecified gestational age. Extensive ossifica- tion defects involving both ends of the femur associated with marked bowing give a ‘chromosome-like’ appearance. b Male fetus at 39 weeks of gestational age. The femur is short, with
splayed metaphyses and central lucent ossification defects ex- tending only slightly into the diaphyses. c Male fetus of un- specified gestational age. Almost normally modeled femoral diaphysis with marked metaphyseal flaring and irregularities.
(From Shohat et al. 1991)
a b c
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