Joints develop secondarily in the mesenchyme com- prised between the developing ends of two adjacent bones (mesenchymal interpose) at about 5 1/2 weeks.
The mesenchyme is converted to form fibrous tissue, hyaline cartilage, or fibrocartilage, depending on whether the developing joint is a fibrous joint, a syn- chondrosis, or a symphysis, respectively. At the site of a synovial joint, while the primitive mesenchyme of the interzone undergoes liquefaction and cavitation, giving rise to the articular cavity, its peripheral con- densation results in formation of the joint capsule (Resnick et al. 1995). This process is completed by ap- proximately 7 weeks of fetal age, and by 8 weeks movements of the limbs about the joint are appear- ing. Motion is essential for the normal development of joints and contiguous structures. As discussed in more detail in the following pages, congenital limita- tion or loss of joint function may be caused by factors that either are intrinsic to the joint, or are extrinsic but inhibit fetal movements.
Reference
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 Joint Motion
The articular abnormalities discussed in this section may occur in association with a great variety of condi- tions and therefore remain totally nonspecific in many cases.Nevertheless,even if the specific diagnosis cannot be determined, a systematic approach to these defects may help to identify broad categories of disorders, to rule out certain diseases, and to provide insight into the anatomical status of individual joints in the body.
This section summarizes the most relevant clini- cal and radiographic patterns of joint involvement, offering existing knowledge of the mechanisms lying behind the altered joint function whenever possible.
Joint Contracture, Joint Stiffness
䉴
[Limitation (loss) of (active and passive) joint motion]
The issue discussed in the current section encom- passes a heterogeneous group of conditions, both in- herited and acquired, isolated and associated with syndromic and nonsyndromic malformation spec- tra, localized to one joint and generalized. An intro- duction to the contractural abnormalities developing after birth is first provided, followed by a discussion of the congenital forms, which represent the main fo- cus of the section.
Flexion contracture and joint stiffness may occur as late manifestations of conditions causing joint and/or surrounding tissue infiltration (sarcoidosis, amyloidosis), hemorrhage (trauma, hemophilia), or inflammation (rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, scleroderma, gout, calcium pyrophosphate dihydrate crystal deposition disease, eosinophilic fasciitis) (Waugh et al. 1980;
Kane-Wanger et al. 1992). Induration and sclerosis of the tendons and ligaments, subcutaneous tissue, and muscles of a given joint may all be responsible for loss of the full range of joint motion. Joint contrac- ture can also follow electrical or thermal burns, pro- longed immobilization (Woo et al. 1975), or end- stage degenerative arthropathy. In amyloidosis, joint contracture may be related to articular and periartic- ular amyloid deposition, muscle or nerve involve- ment, or a combination of factors. Every joint can be affected, including those in the fingers (Bussiere et al.
1976). Several patterns of joint involvement, often
followed by flexion contracture, may occur in pa-
tients with diabetes mellitus, including periarthritis
(stiff shoulder due to capsular fibrosis and thicken-
ing) (Bridgman 1972), cheiroarthropathy (contrac-
tures at the proximal interphalangeal joints, less
commonly at other sites, in the absence of palmar
fascial thickening, tentatively attributed to connec-
tive tissue abnormalities, vascular changes, neuropa-
thy, and myopathy) (Choulot et al. 1980), Dupuytren’s
Alessandro Castriota-Scanderbeg, M.D.
contracture (interphalangeal joint contracture of the 4th and 5th fingers due to thickening of the palmar fascia) (Noble et al. 1984), and flexor tenosynovitis (interphalangeal joint contracture due to a constrict- ed flexor tendon sheath). Multiple joint stiffness and large-joint contractures are manifestations of the autosomal recessive progressive pseudorheumatoid arthropathy (OMIM 208230), a rare skeletal dysplasia with progressive arthropathy mimicking rheumatoid arthritis (Wynne-Davies 1982; Adak et al. 1998). The disease generally manifests between the ages of 3 and
8 years with waddling gait, muscle weakness, and painful swelling of multiple joints, particularly in the hands. Initial symptoms, i.e., morning stiffness and decreased mobility of the cervical spine, suggest rheumatoid arthritis, but synovitis is absent, the sed- imentation rate is within normal range, and rheuma- toid factor tests are negative. Moreover, soft tissues around the joints are not involved, and swelling of the finger joints is caused by osseous expansion of the ends of the phalanges. Arthropathy is character- istically progressive, and affected patients become
Fig. 8.1 a–d. Progressive pseudorheumatoid arthropathy. a In a 13-year-old girl. Note fixed flexion deformity of the knees, hips, elbows and fingers. b–d In a 17-year-old boy. b There is enlargement of the proximal and distal ends of phalanges, joint space narrowing in the carpal, metacarpo-phalangeal,
and interphalangeal joints, and flexion contractures of the fin- gers. There is also diffuse osteoporosis. c Observe severe platyspondyly, irregular end-plates, and anterior vertebral beaking. d Note premature osteoarthritis, deformed femoral capital epiphyses, and coxa vara. (From Kaibara et al. 1983) a
b c
d
crippled because of multiple joint contractures, with fixed flexion deformity of the hips, knees, and el- bows. Roentgenographic changes include general- ized osteoporosis; bulbous enlargement of both ends of the phalanges in the hands; platyspondyly, Scheuermann-like lesions, and kyphoscoliosis in the spine; long bone epiphyseal dysplasia with prema- ture osteoarthritis; and multiple flexion deformities (Fig. 8.1a–d). Universal platyspondyly results in short stature. The head and face are normal (Kaibara et al. 1983; Spranger et al. 1983). Spondylo-epiphyseal dysplasia (Stanescu type) shares several clinical and radiographic features with progressive pseudorheu- matoid dysplasia, including multiple joint swelling and stiffness, progressive joint contractures, platy- spondyly, bulbous widening of the phalanges, and premature osteoarthritis (Fig. 8.2a,b). However, nor- mal height, coxa valga, lack of vertebral tonguing, and autosomal dominant inheritance unambiguously identify patients with Stanescu type of dysplasia (Nishimura et al. 1998). Paradoxical joint stiffness may occur in conditions with joint laxity, such as Ehlers-Danlos syndrome, Marfan syndrome, and ho- mocystinuria. In these disorders, ligamentous laxity and recurrent dislocations lead to precocious os- teoarthritis (during the 3rd or 4th decade of life) and, possibly, to flexion joint contracture. Commonly in- volved joints are the hands, knees, and shoulders (Lewkonia and Pope 1985; Beighton and Horan 1969).
Another potential mechanism is persistent joint effu- sion and hemarthrosis from repetitive subclinical trauma, again caused by ligamentous and capsular laxity (Osborn et al. 1981). It is of interest for the dif- ferential diagnosis that joint contracture occurs only in the 5th digits of the hands in Marfan syndrome, whereas it occurs in multiple digits, the elbows, and the knees in homocystinuria (Brenton et al. 1972).
Congenital joint contractures may be divided in two broad groups, depending on whether the ultimate cause is intrinsic or extrinsic to the developing fetus (Jones 1997). Intrinsic factors include neurological abnormalities, such as anencephaly, microcephaly, hydranencephaly, unilateral cerebral hypoplasia, holoprosencephaly, meningomyelocele, anterior mo- tor horn cell degeneration, aberrant myelin forma- tion, and several others (Hageman et al. 1985, 1988, 1994; Gorgen-Pauly et al. 1999; Borochowitz et al.
1991; Kobayashi et al. 1995; Novotniy 1998); muscle abnormalities, such as fetal myopathies, myotonic dystrophy (Steinert syndrome), myotonic chondro- dystrophy (Schwartz-Jampel syndrome), and muscle agenesis (Jobsis et al. 1999; Hageman et al. 1986;
Wieacker et al. 1985); and joint and/or contiguous tis-
Fig. 8.2 a, b. Spondyloepiphyseal dysplasia, Stanescu type in the 14-year-old boy whose case is illustrated in Fig. 4.32. a Note rela- tively short trunk, flexion contracture of knees, hips, and elbows, and genu valgum. The boy’s height is normal. b Note bulbous ex- pansion of both ends of the phalanges with megaepiphyses, flex- ion of distal interphalangeal joints, and premature osteoarthri- tis. These changes are indistinguishable from those of progres- sive pseudorheumatoid dysplasia. (From Nishimura et al. 1998)
a
b
sue problems, such as lack of joint development, syn- ostosis, congenital skin anomalies (restrictive der- mopathy), aberrant fixation of joints (diastrophic dysplasia), and aberrant soft tissue fixations (pop- liteal pterygium syndrome). In contradistinction, ex- trinsic factors act through a mechanical restriction of the fetus, such as fetal crowding and constraint from any cause (multiple births, oligohydramnios) (Hall 1985). As the term is applied currently, arthrogryposis is not a disease itself, but a birth defect consisting in multiple nonprogressive joint contractures of prena- tal onset. The defect occurs in approximately 1 in 3000
births, and can be seen in isolation or in association with other abnormalities. Over 150 syndromic and nonsyndromic conditions manifest with multiple congenital joint contractures at birth, and the etiolog- ic and genetic basis of these is very heterogeneous (Hall 1985; Ladda et al. 1993; Froster-Iskenius et al.
1988; Herva et al. 1988; Lowry et al. 1985). In a study of 350 patients with various kinds of congenital contrac- tures, 135 (38%) were found to have a specific syn- drome termed amyoplasia (see discussion below); 80 patients (23%) had mental or developmental retarda- tion (11 of these had abnormal karyotypes, about half of them being chromosomal mosaics) (Reed et al.
1985); 11 patients (3%) had multiple limb pterygia (7 of which were instances of the autosomal recessive multiple pterygium syndrome) (Hall et al. 1982b), and 15 patients (4%) had had a possible teratogenic expo- sure during fetal life (infection, maternal drug or tox- in ingestion, chronic maternal illness, or direct physi- cal insult) (Hall and Reed 1982). Regardless of the eti- ology, joint contractures are secondary to fetal akinesia, suggesting that function is an integral part of normal joint development. The clinical phenotype varies according to the underlying etiology, but some features, including equinovarus deformity of the foot, ulnar deviation of the hand, carpotarsal fusions, hip dislocation, patella malposition and dislocation, and scoliosis are common to all types (Hall 1985; Poznan- ski and La Rowe 1970).
A practical approach to the etiology of arthrogry- posis that is useful for estimation of the recurrence risk (including the empiric recurrent risk if a specif- ic diagnosis cannot be reached) and natural history and for decisions on possible therapeutic strategies, consists in identifying children with limb involve- ment only, those with involvement of the limbs and other body areas (trunk, craniofacial or visceral), and those with involvement of the limbs in association with severe central nervous system dysfunction (Hall 1984, 1989). Examples of the first group (limb involve- ment only) include familial camptodactyly, amyo- plasia, trismus-pseudocamptodactyly syndrome, and distal arthrogryposis. Camptodactyly, a peculiar type of localized joint contracture involving the proximal interphalangeal joints of the fingers, is discussed in Chapter 6. Amyoplasia (OMIM 108110) is a sporadic disorder characterized by the absence of limb mus- cles and their replacement by fibrous and fatty tissue.
This is the condition usually meant when the term
‘arthrogryposis multiplex congenita’ is used. At birth, limb positioning is typical: internal rotation of the shoulders, extension of elbows, and flexion of the hands at the wrists. Severe equinovarus deformities
Fig. 8.3 a, b. Amyoplasia (arthrogryposis multiplex congenita) in the 11-year-old boy whose case is illustrated in Fig. 4.38b.
Note a fixed flexion of both hands at the wrist, b equinovarus deformity, and gracile appearance of the tubular bones, espe- cially the fibula. The abnormalities were bilateral and symmet- rical. Additional findings in this boy were bilateral hip sublux- ation (Fig. 4.38b) and scoliosis
a
b
of the feet and contractures at knees and hips are usually present. The face is typically round, with a frontal midline capillary hemangioma and slightly small jaw. Intelligence is normal. Symmetrical limb involvement (four limbs, 63%; lower limbs, 24%; up- per limbs, 13%) and absence of other major malfor- mations are typical (Hall et al. 1983a). Radiographic manifestations include gracile bones, fibular hy- poplasia, scoliosis, dislocation of hip and patella (Fig. 8.3a,b). Identical twins are differently affected (Hall et al. 1983b). ‘Arthrogryposis multiplex con- genita, distal type,’ is a designation for congenital contractures with major involvement of the hands and feet. Arthrogryposis, distal type I (OMIM 108120), a condition of autosomal dominant inheritance with variable expression, manifests at birth with tightly clenched fists with medially overlapping fingers, ulnar deviation, and positional foot deformities (Fig. 8.4). Contractures at other major joints are vari- able. Intelligence is normal, and there are no associ- ated visceral anomalies. Camptodactyly replaces clenched fists in adult life (Hall et al. 1982a). Arthro- gryposis, distal type II (OMIM 108130) occurs in var- ious combinations and patterns with other defects, including fused cervical vertebrae, webbed neck, kyphoscoliosis, congenital hip dislocation, cleft lip and palate, micrognathia, ptosis, trismus, a unique hand position, dull normal intelligence, and short stature (Hall et al. 1982a; Reiss and Sheffield 1986;
Kawira and Bender 1985). Although the pathogenesis of these disorders remains obscure, abnormal ten- don attachments have been implicated (Hall et al.
1982a).
Examples of the second group (involvement of limbs plus other body areas) include congenital con- tractural arachnodactyly, multiple pterygium syn- drome, and Schwartz-Jampel syndrome. Congenital contracture arachnodactyly (Beals syndrome, OMIM 121050) is phenotypically similar to the Marfan syn- drome, with arachnodactyly, dolichostenomelia, pro- gressive kyphoscoliosis, abnormal ears (resembling cabbage leaves), patellar dislocation, and congenital contractures of both hands. With increasing age, the clenched hands of the newborn improve, turning in- to camptodactyly. Contractures of other joints, espe- cially of elbows, are present to varying degrees. A dif- ference from Marfan syndrome is that the aorta and the eyes are not affected. Mutations occurring in two structurally related genes encoding large fibrillin proteins, the FBN1 gene located at 15q15–21.3 and the FBN2 gene located at 5q23–31, cause the Marfan syndrome and the congenital contracture arachno- dactyly, respectively (Lee et al. 1991; Putnam et al.
1995; Babcock et al. 1998). The autosomal recessive multiple pterygium syndrome (Escobar syndrome, OMIM 265000) features multiple pterygia, campto- dactyly and syndactyly. Pterygia occur in the neck, axilla, elbow, popliteal fossa, fingers, and intercrural areas. Affected patients are short, with a characteris- tic facies (down-slanting palpebral fissures, ptosis of eyelids, hypertelorism, epicanthal folds, microg- nathia, down-turned corners of the mouth, sad ex- pression, low-set ears). Additional features include talipes equinovarus and/or rocker-bottom feet, geni- tal anomalies (cryptorchidism, absence of labia ma- jora), and musculoskeletal anomalies (multiple flex- ion contractures, scoliosis, kyphosis, vertebral fu- sions, rib anomalies, absent patella). Occasionally, radial head and hip dislocation, diaphragmatic her- nia, and cardiac defects are also present. Intelligence is normal (Hall et al. 1982b; Escobar et al. 1978).
Schwartz-Jampel syndrome (chondrodystrophia my- otonica, OMIM 255800), also of autosomal recessive inheritance, is characterized by myotonia, blepharo- phimosis, and joint contractures. A primary muscle disorder with hypotonia is possibly responsible for most of the clinical features. In fact, early diagnosis and treatment with carbamazepine can resolve my- otonia and prevent the development of the classic clinical picture. Manifestations of the disorder in- clude short stature, expressionless fixed face, pursed lips, narrowed palpebral fissures, small mandible, myopia, spinal malalignment, pectoral deformity, ac- etabular dysplasia, and bowed long bones (Schwartz and Jampel 1962; Squires and Prangley 1996). Mental retardation is present in 25% of cases. The disease
Fig. 8.4. Arthrogryposis, distal type I in a 4 1/2-year-old boy.
Note clenched hands with medially overlapping fingers and ul- nar deviation of the fingers. Flexion deformities and contrac- tures similar to those in the hands were evident in the feet (not shown). No other skeletal or visceral anomalies were present
course is one of progressive muscle weakness and joint contractures reaching a plateau in mid-child- hood.
Examples of the third group of arthrogrypotic dis- orders (limb involvement plus central nervous sys- tem problems) are the Marden-Walker syndrome and the Pena-Shokeir syndrome. Clinical manifesta- tions in Marden-Walker syndrome (OMIM 248700), an autosomal recessive disorder, include fixed facial expression, blepharophimosis, and joint contrac- tures. Central nervous system defects include agene- sis of corpus callosum, cerebellar hypoplasia, brain stem hypoplasia, hydrocephalus, and Dandy-Walker malformation. Micrognathia, decreased muscle mass with hypotonia, microcephaly, and mental retarda- tion are also part of the syndromic spectrum. Death within the first months of life is relatively common, occurring as a secondary event of aspiration, sepsis, or cardiac failure (Marden and Walker 1966). ‘Pena- Shokeir’ is often used as an aspecific label for a clini- cal phenotype caused by decreased intrauterine movement, regardless of the specific cause. There- fore, the designations ‘Pena-Shokeir phenotype’ and
‘fetal akinesia/hypokinesia sequence’ may be used interchangeably (Hall 1986). The Pena-Shokeir phe- notype occurs in a group of etiologically heteroge- neous disorders. When fully expressed, this pheno- type is characterized by polyhydramnios, intrauter- ine growth retardation, pulmonary hypoplasia, craniofacial and limb anomalies, multiple congenital contractures, short umbilical cord, and lethality (Herva et al. 1985). Polyhydramnios is the result of failure of normal deglutition, lung hypoplasia, or de- ficient function of the diaphragm and intercostal muscles. The short umbilical cord and the multiple joint contractures are caused by the absence of fetal movements. Hence, overlap with arthrogryposis multiplex congenita is recognized. The unusual fa- cies and lethality in Pena-Shokeir allow the differen- tial diagnosis. Furthermore, interphalangeal sublux- ation has been reported as a potentially specific sign of Pena-Shokeir (Houston and Shokeir 1981). Over- lap is also recognized between the Pena-Shokeir phe- notype and trisomy 18 (Jones 1997).
Radiographic Synopsis
Evaluation of the skeleton aims at verifying whether joint fixation is due to an anatomic anomaly (for ex- ample, congenital synostosis) or to a deficit of joint function in the absence of primary structural causes.
In joint contractures occurring as part of a primary disease the radiographic findings are those of the un- derlying disease process.
1. Multiple flexion deformities; widening of meta- physes and epiphyses of the phalanges; platy- spondyly; premature osteoarthritis; osteoporosis (progressive pseudorheumatoid arthropathy) 2. Flexion contracture of the interphalangeal joint of
the 5th digits; arachnodactyly; dolichostenomelia;
patella dislocation (Marfan syndrome)
3. Multiple, symmetrical joint contractures, com- monly involving all four limbs (shoulders, elbows, hands, wrists, knees and hips); severe foot equino- varus; absent limb muscles; gracile bones; fibular hypoplasia; scoliosis; hip and patella dislocation (amyoplasia)
4. Congenital contractures of the fingers and toes, isolated (arthrogryposis, distal type I) or associat- ed with fused cervical vertebrae, kyphoscoliosis, congenital hip dislocation, cleft lip and palate, and micrognathia (arthrogryposis, distal type II) 5. Arachnodactyly; dolichostenomelia; progressive
kyphoscoliosis; patellar dislocation; congenital contractures of both hands, camptodactyly (con- genital contracture arachnodactyly)
6. Multiple flexion contractures; multiple pterygia;
camptodactyly and syndactyly; characteristic fa- cies (multiple pterygium syndrome)
7. Joint contractures; myotonia; blepharophimosis (Schwartz-Jampel syndrome)
8. Joint contractures; fixed facial expression; ble- pharophimosis (Marden-Walker syndrome) 9. Multiple congenital joint contractures; pulmonary
hypoplasia; unusual facies; lethality (Pena-Shokeir syndrome)
Associations
• Aarskog syndrome
• Aase-Smith syndrome
• Achondroplasia
• Acromesomelic dysplasia
• Addison disease
• Adducted thumb syndrome
• Amyloidosis
• Amyoplasia congenita disruptive sequence
• Antley-Bixler syndrome
• Apert syndrome
• Aplasia cutis congenita
• Arthrogryposis, distal, types I and II
• Arthrogryposis-advanced skeletal maturation- unusual facies
• Camptodactyly-ichthyosis syndrome
• Catel-Manzke syndrome
• Caudal dysplasia sequence
• Cerebro-oculo-facio-skeletal syndrome
• CHILD syndrome
• Chondrodysplasia punctata (recessive, X-linked dominant)
• Chromosomal abnormalities (trisomy 8,trisomy 9, mosaic, 13, trisomy 18, XXXXY, deletion 11q, duplication 4p, duplication 10q, duplication 15q)
• Cockayne syndrome
• Contractural arachnodactyly, congenital (Beals syndrome)
• De Lange syndrome
• Dermo-chondro-corneal dystrophy of François
• Diabetes mellitus
• Diastrophic dysplasia
• Digitotalar dysmorphism
• Duchenne muscular dystrophy
• Dyggve-Melchior-Clausen syndrome
• Dyschondrosteosis
• Dysplasia epiphysealis hemimelica
• Dyssegmental dysplasia
• Epidermolysis bullosa dystrophica
• Exostoses
• Fabry disease
• Farber disease
• Femoral hypoplasia-unusual facies syndrome
• Fetal-alcohol syndrome
• FG syndrome
• Fibrochondrogenesis
• Fibrodysplasia ossificans progressiva
• Fluorosis
• Flynn-Aird syndrome
• Freeman-Sheldon syndrome
• Frontometaphyseal dysplasia
• Geleophysic dysplasia
• German syndrome
• GM1 gangliosidosis
• Golden-Lakim syndrome
• Goodman camptodactyly syndrome
• Gordon syndrome
• Hecht syndrome
• Hemophilia
• Homocystinuria
• Hypochondroplasia
• Infantile multisystem inflammatory disease
• Killian/Teschler-Nicola syndrome
• Klein-Waardenburg syndrome
• Kniest dysplasia
• Kuskokwim syndrome
• Kyphomelic dysplasia
• Leri-Weill dyschondrosteosis
• Macrodystrophia lipomatosa
• Mandibuloacral dysplasia
• Marden-Walker syndrome
• Melorheostosis
• Metaphyseal chondrodysplasias (Jansen, McKusick, Schmid)
• Metatropic dysplasia
• Mietens-Weber syndrome
• Moore-Federman syndrome
• Mucolipidoses
• Mucopolysaccharidoses
(Hunter, Hurler, Morquio, Maroteaux-Lamy)
• Multiple epiphyseal dysplasia
• Multiple pterygium syndrome (Escobar syndrome)
• Multiple synostoses syndrome (facio-audio-symphalangism)
• Myhre syndrome
• Nail-patella syndrome
• Neu-Laxova syndrome
• Oligohydramnios sequence
• Oto-palato-digital syndrome type I
• Pachydermoperiostosis
• Pallister-Hall syndrome
• Parastremmatic dwarfism
• Pelvic dysplasia-arthrogrypotic lower limbs
• Pena-Shokeir syndrome
• Pleonosteosis (Leri)
• Popliteal pterygium syndrome
• Progeria
• Progressive pseudorheumatoid chondrodysplasia
• Pseudoachondroplasia
• Pseudodiastrophic dysplasia
• Pyle metaphyseal dysplasia
• Restrictive dermopathy
• Rigid spine syndrome
• Rutledge lethal congenital anomaly syndrome
• Saethre-Chotzen syndrome
• Schwartz-Jampel syndrome
• Scleroderma
• Seckel syndrome
• Shprintzen-Goldberg syndrome
• Sjögren-Larsson syndrome
• Spondylocostal dysplasia, Jarcho-Levin
• Spondyloepiphyseal dysplasia congenita
• Spondyloepiphyseal dysplasia (Stanescu)
• Spondylometaphyseal dysplasia (Kozlowski)
• Stewart-Bergstrom syndrome
• Stickler syndrome
• Trismus pseudocamptodactyly syndrome (Hecht)
• Tumoral calcinosis
• Weaver syndrome
• Weill-Marchesani syndrome
• Winchester syndrome
• Zellweger syndrome
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Ankylosis
䉴
[Joint fixation]
Although ankylosis and synostosis are often used as synonyms, each term implies a distinct mechanism of joint fixation. Synostosis indicates a failure of joint formation, while the true meaning of ankylosis is supervening fixation of a previously normally de- veloped joint. The radiographic and pathological aspects related to the presence of synostosis at specif- ic articular sites are discussed elsewhere in this book.
Similarly, congenital disease processes manifesting with multiple synostoses, such as Antley-Bixler syn- drome, Apert acrocephalosyndactyly, and multiple synostosis syndrome, are also not included here.
Ankylosis can be due to calcium deposition in the joint or in the soft tissues surrounding the joint. A number of inflammatory and connective tissue disor- ders are recognized in which joint ankylosis may be part of the clinical spectrum. In advanced rheumatoid arthritis, the proliferative granulation tissue – or pan- nus, the pathological hallmark of the disease – can ex- tend across the joint bridging the articular cavity. By calcification of the dystrophic tissue that bounds the articular cartilages of opposing bones, the initial fi- brous ankylosis is transformed into bony ankylosis.
The disease has a predilection for the synovial articu- lations of the appendicular skeleton, especially those in the hands and feet, wrist, knee, elbow, glenohumer- al and acromioclavicular joints. However, the at- lantoaxial joint and apophyseal joints of the cervical spine can also be involved. Bony proliferation with in- tra-articular bony ankylosis frequently occurs in the seronegative spondyloarthropathies (ankylosing spondylitis, psoriasis, and Reiter’s disease), a group of inflammatory disorders sharing radiologic and pathological similarities with rheumatoid arthritis, but with prominent involvement of the cartilaginous articulations (discovertebral junctions, symphysis pubis, manubriosternal joint) and entheses (tendi- nous and ligamentous attachments in the calcaneus, pelvis, femoral trochanters, humerus, patella, etc.).
The sites primarily affected by ankylosing spondylitis are the joints and entheses of the axial skeleton. Psori- asis has a variable distribution, but is essentially a polyarticular disorder of appendicular joints, with prominent involvement of the interphalangeal articu- lations of the hands and feet. In Reiter’s disease, asymmetrical involvement of the joints in the lower extremities, sacroiliitis, spondylitis, and calcaneal en- thesopathy are common manifestations. Intra-articu- lar bony ankylosis is relatively common in juvenile chronic arthritis, including the juvenile-onset adult type (seropositive) of rheumatoid arthritis, seronega- tive juvenile chronic arthritis (Still’s disease), and ju- venile-onset ankylosing spondylitis, and also in septic arthritis. In the spine, obliteration of intervertebral disc spaces and bony bridging resulting in ankylosis of contiguous vertebrae also occurs in some cases of alkaptonuria, X-linked hypophosphatemia, calcium pyrophosphate dihydrate (CPPD) crystal deposition disease (Brem 1982), and (occasionally) severe degen- erative osteoarthritis.
A mixed pattern of intra-articular and periarticu-
lar soft tissue (tendons, tendon sheaths, capsule, bur-
sae) calcification (Resnick et al. 1977; Albert and Ott
1984) is characteristic of scleroderma, a generalized
disorder of connective tissue that affects the skin,
lungs, gastrointestinal tract, heart, kidney, and mus- culoskeletal system. Articular involvement is com- mon in scleroderma, with preferential locations in the fingers, wrists, and ankles. Erosive arthritis of the distal interphalangeal joints (Resnick 1995; Baron et al. 1982; Bassett et al. 1981), articulations that are not commonly involved in rheumatoid arthritis, of the proximal interphalangeal, metacarpophalangeal, 1st carpo-metacarpal, and inferior radioulnar joints, which can culminate in bony ankylosis, can all be seen in scleroderma (Jamieson et al. 1985; Resnick et al. 1978; Bjersand 1968). Ankylosis of such major joints as the elbows and hips also occurs (Huyck and Hoffman 1982). Mixed connective tissue disease is the designation for a condition characterized by overlap- ping clinical features of scleroderma, systemic lupus erythematosus, dermatomyositis, and rheumatoid arthritis and by a feature revealed by laboratory in- vestigations in all cases: the presence of antibodies to RPN, a soluble ribonucleoprotein (Sharp et al. 1972;
Bennett and O’Connell 1978; Notman et al. 1975;
Alarcon-Segovia 1981). Ankylosis at the capitate- trapezoid articulation could possibly have clinical significance (Halla and Hardin 1978).
As anticipated, ankylosis can also be due to bridg- ing heterotopic calcific or ossific deposits within the soft tissues surrounding the joint even when the joint itself is not primarily affected. Examples include trau- ma (myositis ossificans), neurological injury, postsur- gical scars, and thermal and electrical burns (Fig. 8.5).
Thermal and electrical injuries affect the elbow, shoul- der, and hip most frequently, irrespective of their proximity to the burn site. If the joint is directly dam- aged by the burn intra-articular fusion may ensue.
Progressive heterotopic ossification of muscles, tendons, ligaments, fasciae, aponeuroses and, occa- sionally, the skin in combination with bilateral short hallux is the clinical and pathological hallmark of fibrodysplasia (or myositis) ossificans progressiva syndrome (OMIM 135100), an inheritable connective tissue disorder (McKusick 1972). The inheritance pattern is autosomal dominant (the disease gene maps to 4q27-q31) (Feldman et al. 2000; Lucotte et al.
2000), with almost full penetrance for short hallux and wide variability for fibrodysplasia (McKusick 1972; Jones 1997). Most cases are sporadic, represent- ing spontaneous fresh mutations (Rogers and Geho 1979; Connor and Evans 1982; Connor et al. 1993) probably related to paternal age (Rogers and Chase 1979; Tuente et al. 1967). The prevailing pathogenetic theory, which is not shared by all investigators (Smith 1998), is one of primary involvement of the fibrous tissue, with secondary extension to the striate mus- cles through the contiguous fascial coverings (McKu- sick 1972; Reinig et al. 1986; Kalukas and Adams 1985). Histological changes at the involved sites include edema, fibroblast proliferation, muscular cell degeneration, and deposition of abnormal colla- gen, which subsequently undergoes mineralization (Cramer et al. 1981; Kaplan et al. 1993). The newly formed bone is entirely identical to normal membra- nous bone. The initial clinical presentation includes swelling, local warmth, pain, and fever, mimicking an infection, a trauma, or a neoplasm. Common sites of initial heterotopic ossification are neck (sternoclei- domastoid), shoulder girdle, spine, and pelvis. The distal extremities are involved late in the course of the disease. An entire muscle or group of muscles can be replaced by bone. The smooth muscles are spared.
Joint ankylosis is caused by ossification of the sur- rounding tissues, as opposed to a primary articular abnormality. Various postural deformities develop as the result of joint ankylosis. Ankylosis of the tem-
Fig. 8.5. Electrical burn in a 34-year-old man. Note extra-ar- ticular heterotopic ossification leading to lateral osseous bridging of the hip. (From Balen et al. 2001)
poromandibular joint limits nutrition, while involve- ment of the hips leaves the patient wheelchair bound (Connor and Evans 1982; Cohen et al. 1993). Hearing loss is common. Most patients experience symptom onset at about 5 years of age. Restricted mobility of a single or of multiple joints is apparent within 15 years in the vast majority of patients (Cremin et al.
1982). The natural history of the disease is one of re-
current remissions and exacerbations (Cohen et al.
1993). Radiographic manifestations include bilateral short hallux (90%), often with interphalangeal fu- sions; hallux valgus; short thumbs (about 50%);
cylindrical columns of solid new bone replacing an entire muscle or group of muscles; ‘pseudoexostoses’
at the insertions of tendons, ligaments, and fasciae;
progressive intervertebral fusions (especially in the
Fig. 8.6 a–e. Fibrodysplasia ossifi- cans progressiva. a In a 17-year-old male youth. Note short great toe with interphalangeal fusion. The phalanges are in mild valgus devia- tion. b–e In a 6-year-old girl. b Bony outgrows arising from the tibial metaphysis and reminiscent of os- teochondromas. Note also mature trabecular heterotopic ossification bone in the axilla (c), iliopsoas mus- cles (d), and nuchal ligament (e).
(From Mahboubi et al. 2001)
a b
d e
c
cervical spine); and ossification of the spinal liga- ments (Fig. 8.6a–e). Occasionally X-rays show short middle phalanges of the 5th fingers and toes with clinodactyly; malformed cervical vertebrae; broad femoral necks; cortical thickening of both tibias;
broad mandibular condyle; spina bifida; scoliosis;
and lumbar spinal stenosis (Cremin et al. 1982;
Thickman et al. 1982). The trabecular pattern of the heterotopic bone in this condition allows its distinc- tion from other disorders with periarticular calcium deposition, including idiopathic calcinosis univer- salis, dermatomyositis, idiopathic tumoral calcinosis, and disorder of calcium metabolism, in which the dense lesions remain calcific and do not mature into trabecular bone. Disorders such as Klippel-Feil, Still’s disease, and ankylosing spondylitis, which share sim- ilarities with fibrodysplasia progressive ossificans at the spinal level, can be easily ruled out by ascertain- ing the absence of the typical anomalies involving the great toes, which are present and potentially rec- ognizable at birth in all cases of fibrodysplasia ossifi- cans progressiva (Smith et al. 1996).
Radiographic Synopsis
1. Symmetrical involvement of the synovial joints of the appendicular skeleton (hands, feet, wrists, knees, elbows, and shoulders most involved); soft tissue swelling; osteoporosis; joint space narrow- ing; marginal bony erosions; subchondral cyst for- mation; joint ankylosis, deformity, and dislocation (rheumatoid arthritis)
2. Synovial and cartilaginous articulations involved;
preferential involvement of the joints in the axial skeleton (sacroiliac, apophyseal, discovertebral, and costovertebral articulation); characteristic pattern of spinal ascent; involvement of entheses;
joint space narrowing and erosion; marginal scle- rosis; bone formation within joint capsule, ten- dons, and ligaments; joint ankylosis (ankylosing spondylitis)
3. Synovial and cartilaginous articulations involved;
asymmetrical involvement of the appendicular (upper and lower limb) and axial joints; promi- nent involvement of the interphalangeal articula- tions of hands and feet; osteolysis of terminal phalanges; bone formation within joint capsule, tendons, and ligaments; intra-articular bony anky- losis (psoriasis)
4. Synovial and cartilaginous articulations involved with findings reminiscent of psoriasis; asymmet- rical involvement of the appendicular (lower limb) and axial joints; calcaneal enthesopathy;
resolution of some lesions (Reiter’s disease)
5. Erosive arthritis of the distal and proximal inter- phalangeal joints, metacarpophalangeal joints, 1st carpometacarpal joints, and inferior radioulnar joints; tuftal resorption; skin atrophy; soft tissue calcification (scleroderma)
6. Bilateral short hallux; short thumbs (less com- mon); heterotopic ossification of striate muscles;
‘pseudoexostoses’ at insertion points of tendons, ligaments, fasciae, and aponeuroses; ankylosis of spine, shoulders, hips, temporomandibular joints, etc. (fibrodysplasia ossificans progressiva syndrome)
Associations
• Alkaptonuria
• Ankylosing spondylitis
• Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease
• Degenerative osteoarthritis
• Fibrodysplasia ossificans progressiva syndrome
• Hemophilia
• Juvenile chronic arthritis
• Mixed connective tissue disease
• Neurological injury
• Osteogenesis imperfecta
• Psoriasis
• Reiter’s disease
• Rheumatoid arthritis
• Scleroderma
• Septic arthritis
• Surgical scars
• Thermal and electric burns
• Trauma
• Winchester syndrome
• X-linked hypophosphatemia
References
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Balen PF, Helms CA. Bony ankylosis following thermal and electrical injury. Skeletal Radiol 2001; 30: 393–7
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Bjersand AJ. New bone formation and carpal synostosis in scleroderma. A case report. Am J Roentgenol Radium Ther Nucl Med 1968; 103: 616–9
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Cramer SF, Ruehl A, Mandel MA. Fibrodysplasia ossificans progressiva: a distinctive bone-forming lesion of the soft tissue. Cancer 1981; 48: 1016–21
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Joint Laxity, Joint Hypermobility
䉴
[Hyperextensible joints, increased range of joint motion]
The osseous surfaces of a synovial articulation are bound together by a fibrous capsule externally rein- forced by a variety of supporting structures (ten- dons, aponeuroses, fasciae, and ligaments) and, at some joint sites, by accessory intra-articular liga- ments (e.g., the cruciate ligaments of the knee). The fibrous capsule represents the outer layer of the artic- ular capsule (the inner layer being the synovial mem- brane) and is composed of parallel and interlacing thick bundles of connective tissue. The ligaments are tough bands of connective tissue that resist excessive or abnormal motion and are therefore essential to the maintenance of joint stability (Resnick and Ni- wayama 1995).
In disorders of the connective tissue with joint
laxity, the articular capsule, the ligaments, and the
periarticular supporting tissues are all involved by
the primary mesenchymal defect. In the Ehlers-Dan-
los syndromes, a group of disorders with impaired
collagen synthesis (Beighton et al. 1969; McKusick
1972; Prockop and Kivirikko 1984; Kivirikko and Ris-
teli 1966) characterized by disorganization of colla-
gen bundles and abnormal shortening of the colla-
gen chains (Svane 1966; Rybka and O’Hara 1967),
joint hyperextensibility, skin fragility/hyperelasticity,
and vascular fragility with bleeding diathesis are car-
dinal features, whereas primary osseous abnormali- ties are absent. Ligamentous and capsular laxity leads to kyphoscoliosis, pes planus, spondylolisthesis, and genu recurvatum (Beighton et al. 1969; Lewkonia and Pope 1985; Bannerman et al. 2000; Pyeritz 2000).
Other organs and systems are involved to variable extents, including the eye, gastrointestinal tract, bronchopulmonary tree, genitourinary system, and cardiovascular system (Schippers and Dittler 1989).
Unlike Marfan syndrome and homocystinuria, dolichostenomelia is not an obligatory finding. The label ‘Ehlers-Danlos syndrome’ refers in fact to a group of nine syndromes (Beighton et al. 1998) that share the same complex of clinical abnormalities, while differing in both genetic and biochemical char- acteristics. Unclassified forms and overlapping syn- dromes (e.g., Ehlers-Danlos type VII and osteogene- sis imperfecta) exist (Ainsworth and Aulicino 1993;
Hartsfield and Kousseff 1990; Wordsworth et al. 1991;
Hamada et al. 1992). Both active and passive joint hypermobility of severe degree is observed in type I (OMIM 130000), type III (OMIM 130020), and type VII (OMIM 130060) (Lacour 1998; Giunta et al. 1999;
McKusick 1974) Ehlers-Danlos syndrome. Sponta- neous dislocations are common and correlate with the degree of laxity (Beighton and Horan 1969a).
Sites of dislocation are both small and large joints, including the hands, the radial head, the hip, and the patellofemoral, glenohumeral, temporomandibu- lar, sternoclavicular, and acromioclavicular joints (McKusick 1972; Beighton and Horan 1969b; Horton et al. 1980; Carter and Wilkinson 1964). Recurrent dislocations cause premature degenerative joint dis- ease (Osborn et al. 1981). Persistent effusions or hemarthroses, which are also thought to result from repetitive subclinical trauma caused by ligamentous and capsular laxity, may contribute to the precocious occurrence of degenerative joint disease. Secondary changes of the articular constituents, with articular cartilage degeneration, capsular thickening, and contractures, can be responsible for switching from joint laxity to joint stiffness in the advanced stages (Beighton and Horan 1969a). The carpometacarpal joint of the thumb is particularly vulnerable (Gold- man 1995; Gamble et al. 1989). In Marfan syndrome (OMIM 154700) the eye, the skeleton, and the cardio- vascular system are primarily involved. Despite wide variability of the clinical phenotype, ectopia lentis, aortic root dilatation or dissection, dolichosteno- melia, and dural ectasia are consistent features of the syndrome (Tsipouras 1992; Tsipouras et al. 1992;
Morse et al. 1990; Joseph et al. 1992). Mutations in the gene encoding fibrillin (FBN1, locus maps to 15q15–
15q21) result in Marfan syndrome (Tsipouras et al.
1992; Kainulainen et al. 1990; Sarfarazi et al. 1992).
Fibrillin is a component of elastin fibrils, which are found in the tunica media of the aorta, periosteum, and ligaments (Tsipouras et al. 1992). Marfan syn- drome and congenital contractural arachnodactyly, a milder disorder without major involvement of the eyes and aorta, are phenotypically and genetically re- lated disorders. However, while the mutant gene in the Marfan syndrome (FBN1) is located on chromosome 15, the disease locus in congenital contractural arachnodactyly (FBN2) is located on chromosome 5.
Similarly, isolated mitral valve prolapse does not ap- pear to be linked to the fibrillin gene on chromosome 15. Manifestations of ligamentous laxity and joint hy- permobility include scoliosis (frequent), pes planus deformity (frequent) (Pyeritz and McKusick 1981), joint dislocation (patellas, hips, clavicles, mandible), joint deformation (genu recurvatum, patella alta), and premature osteoarthritis (Magid et al. 1990;
Pennes et al. 1985; Walker et al. 1969).Atlantoaxial dis- location is rare (Levander et al. 1981). Homocystinuria (OMIM 236200) is a heterogeneous group of inherit- ed disorders of the connective tissue, with abnormal- ities involving the central nervous system (variable mental retardation, seizures); the vasculature (fibrous medial degeneration of the aorta and other arteries, arterial and venous thrombosis); the eyes (bilateral lens subluxation, myopia, less frequently cataracts and optic atrophy); the skeleton (slim long bones, arachnodactyly, pectus carinatum or excavatum, pes cavus, kyphoscoliosis, osteoporosis, multiple contrac- tures); the skin (thin skin, malar flush, prominent ve- nous markings, ‘cigarette paper’ scars); and the hair (fine, sparse, dry, and light) (Schoonderwaldt et al.
1981; Isherwood 1996; Beals 1969). Manifestations of
joint laxity, such as genu valgum and patella alta, are
not consistently present (Brenton et al. 1972; Skovby
1989; Smith 1967; Hurwitz et al. 1968; Leonard 1973)
and, a point that is of interest for the differential diag-
nosis against Marfan syndrome, they coexist with
flexion contractures of the fingers, elbows and knees
(in Marfan syndrome, contracture occurs in the 5th
digit only) (Beals 1969; Brenton et al. 1972). Other dis-
tinctive features in homocystinuria include mental
retardation, malar flush, vascular thromboses, and ec-
topia lentis at birth (Goldman 1995). Ligamentous
laxity and bone fragility are characteristic clinical as-
pects of osteogenesis imperfecta (OMIM 166200,
166210, 166220, 259420), an inherited connective tis-
sue disorder with a defect in fibrillar type I collagen
synthesis (Stoltz et al. 1989; Marini 1988; Rosenstock
1968; Brenner et al. 1989a, b), a major component of
the bone organic matrix (Nerlich et al. 1993). Type I collagen is also highly represented in ligaments, ten- dons, fasciae, sclerae, and teeth. As stated earlier, Ehlers-Danlos type VII is another disorder related to mutations of type I collagen. Blue sclerae, a common finding in osteogenesis imperfecta, can also occur in Ehlers-Danlos type VII (Cohn and Byers 1990; Pope et al. 1989; Byers 1990; Sykes 1993). Despite these simi- larities, and the occurrence in patients with osteogen- esis imperfecta of the clinical abnormalities that are typical for connective tissue disorders, including joint laxity and hypermobility, no increase in the preva- lence of dislocations has been reported in osteogene- sis imperfecta (Gertner and Root 1990). Similarly, bleeding is less constant and severe in osteogenesis imperfecta than in Ehlers-Danlos syndromes (Gert- ner and Root 1990; Beighton et al. 1983; Ramser et al.
1966). Joint laxity is most prominent in osteogenesis imperfecta type I and type III of the Sillence classifi- cation (Sillence et al. 1979). Severe kyphoscoliosis and genu valgum may arise from ligamentous and capsu- lar laxity or fracture deformities, or a combination of the two. Joint laxity, familial (articular hypermobility syndrome, OMIM 147900), a condition formerly in- cluded under the Ehlers-Danlos umbrella (Ehlers- Danlos syndrome type XI), is now recognized as a separate disorder of autosomal dominant inheritance characterized by joint laxity and congenital hip dislo- cation (Horton et al. 1980) and not including the skin changes that are part of the spectrum of the Ehlers- Danlos syndromes (Beighton et al. 1998). Recurrent dislocation of other joints, including the patella and the shoulder, may also be observed. Ligamentous and capsular laxity, with dislocated hips at birth and ear- ly-onset, progressive kyphoscoliosis, is also observed in spondyloepimetaphyseal dysplasia with joint laxity (OMIM 271640). Joint laxity and dislocation (at- lantoaxial, hip) are prominent findings in Down syn- drome (OMIM 190685). In this regard, the dispute prompted by the ‘triple jeopardy’ of the upper cervical spine (atlantoaxial subluxation, hypoplastic posterior arch of C1, and atlanto-occipital instability) on whether or not children with Down syndrome should be screened radiographically remains unresolved (Kriss 1999).
Radiographic Synopsis
1. Joint hyperextensibility; skin fragility/hyperelas- ticity; vascular fragility; joint dislocation; kypho- scoliosis; pes planus; spondylolisthesis; genu re- curvatum; premature osteoarthritis (Ehlers-Dan- los syndrome)
2. Ectopia lentis; aortic dilatation/dissection; do- lichostenomelia; dural ectasia; joint dislocation;
kyphoscoliosis; pes planus; genu recurvatum;
patella alta; premature osteoarthritis (Marfan syn- drome)
3. Ectopia lentis; mental retardation; vascular throm- bosis; dolichostenomelia; arachnodactyly, joint contractures; patella subluxation; pes cavus;
kyphoscoliosis; thin skin; sparse fine hair (homo- cystinuria)
4. Joint laxity; multiple fractures; kyphoscoliosis;
genu valgum (osteogenesis imperfecta) Associations
• Aarskog syndrome
• Achard syndrome
• Acromesomelic dysplasia
• Bannayan-Riley-Ruvalcaba syndrome
• Borjeson-Forssman-Lehmann syndrome
• Chromosome XXXXY syndrome
• Coffin-Lowry syndrome
• Coffin-Siris syndrome
• Cohen syndrome
• Cutis laxa
• Cutis laxa-growth deficiency syndrome
• Deafness and metaphyseal dysostosis
• Down syndrome
• Ehlers-Danlos syndromes
• FG syndrome
• Floating-Harbor syndrome
• Focal dermal hypoplasia (Goltz-Gorlin syndrome)
• Fragile X syndrome
• Geroderma osteodysplastica hereditaria
• Hajdu-Cheney syndrome
• Hallermann-Streiff syndrome
• Homocystinuria
• Hypermobility syndrome
• Hypochondroplasia
• Johanson-Blizzard syndrome
• Joint laxity-idiopathic scoliosis
• Kabuki syndrome
• Langer-Giedion syndrome
• Larsen syndrome
• Lenz-Majewski syndrome
• LEOPARD syndrome
• Lowe syndrome
• Marfan syndrome
• Marfanoid hypermobility syndrome
• Megaepiphyseal dysplasia-wrinkled skin-aged appearance
• Metaphyseal chondrodysplasia, McKusick
• Metatropic dysplasia
• Mitral valve prolapse, isolated
• Mucopolysaccharidosis IV A (Morquio)
• Multiple endocrine neoplasia, type 2b
• Nail-patella syndrome
• Osteogenesis imperfecta, type I
• Osteoporosis-pseudoglioma syndrome
• Pallister-Killian syndrome
• Pseudoachondroplasia
• Robinow syndrome
• Rubinstein-Taybi syndrome
• Seckel syndrome
• Shprintzen syndrome
• Spondyloepimetaphyseal dysplasia with joint laxity
• Spondyloepiphyseal dysplasia
• Stickler syndrome
• The 3-M syndrome
• Tricho-rhino-phalangeal dysplasia, type 2
• Velo-cardio-facial syndrome
• Wrinkly skin syndrome
• Zimmermann-Leband syndrome
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