Syndromes of Orthopaedic Importance

The diagnosis is made on the basis of family history and
clinical findings, including abnormalities in the ocular, cardiac, and
musculoskeletal systems (13). Several meetings
have been held recently in an attempt to come to a consensus about
diagnostic criteria. Unfortunately, controversy

remains
as to the best set of diagnostic criteria to employ: the more stringent
criteria exclude many individuals who are currently managed as Marfan
syndrome patients. The less stringent Berlin criteria and more
stringent Ghent criteria are outlined in Table 9.1 (14,15,16).
To further confound issues of diagnosis, dural ectasia, which is a
major diagnostic criterion, is defined as a dural volume greater than 7
cm³ below the inferior L5 endplate; this measurement
requires a magnetic resonance image (MRI) study to be performed, using
a technique that allows for this volume to be measured (17,18).
In addition, the normal dural volume in younger, growing children is
not known, and the reliability and reproducibility of volume measures
when used outside of clinical investigative groups is not known.

There are a variety of additional physical findings that
are suggestive of Marfan syndrome and, although not considered part of
the diagnostic criteria, should alert one to consider this diagnosis.
It was thought that the physical finding of an arm span longer than
height would be diagnostic of Marfan syndrome; however, population
studies have shown that this is not the case. The ratio of upper
segment (head to pubic symphysis) to lower segment (pubic symphysis to
plantar surface), which is normally 0.93 in a mature individual, is
often decreased in Marfan syndrome to 0.85 or less (19).
Two clinical findings associated with arachnodactyly are a thumb that
protrudes past the ulnar border of the hand when it is held in a
clenched fist (Steinberg sign) and overlap in the thumb and index
finger when they are wrapped around the opposite wrist (20).

Although there are a variety of radiographic findings
that are frequently present in patients with Marfan syndrome, these are
not pathopneumonic. Spinal morphology suggestive of dural ectasia and
pedicle dysplasia are suggestive of this disorder. The use of
measurements from spine radiographs in making this diagnosis (an
interpedicular distance at L5 greater than or equal to 36.0 mm; a
sagittal diameter at L5 greater than or equal to 13.5 mm; a transverse
process-to-vertebral width ratio at L3 greater than or equal to 2.25
mm) yields a high sensitivity, but a relatively poor specificity (16).
Arachnodactyly is defined, for purposes of radiographic readings, as an
increase in the ratio of length to width of the second to fifth
metacarpals (Fig. 9.2). The average ratio of
the lengths of the second to fifth metacarpals, divided by the widths
of the respective diaphyses, is greater than 8.8 in male patients and
greater than 9.4 in female patients with Marfan syndrome (21).
There are no studies, however, that determine the sensitivity and
specificity of the use of these measures to make a diagnosis of Marfan
syndrome.

Marfan syndrome is inherited in an autosomal dominant manner and is caused by mutations in the fibrillin gene (22).
Thirty percent of the cases, however, are sporadic. The current
evidence points to a dominant-negative effect, in which expression of
the mutant gene product inactivates the function of the normal gene
product. As such, this condition could potentially be treated by the
use of therapies that decrease the expression of the mutant gene (23).
The fibrillin protein plays a role in maintaining the normal mechanical
properties of the soft tissues, especially in resistance to cyclic
stress (24). The clinical findings of laxity
and subluxation of the joints, and weakening of arterial walls with
resultant aortic dilatation, are easy to understand on the basis of the
function of fibrillin. The tall stature and arachnodactyly associated
with the syndrome are seemingly difficult to attribute to the fibrillin
mutation. However, the extracellular matrix also contains growth
factors, which are bound to extracellular matrix proteins. Recent
investigations have found that fibrillin mutations cause some of these
extracellular growth factors, such as transforming growth factor β to
become more readily accessible to cell receptors (25).
The increased growth factor availability likely causes increased
cellular growth and rapid longitudinal bone growth, resulting in long,
thin fingers and toes and tall stature. Although molecular diagnosis
for fibrillin gene mutations is possible, such use of molecular data is
usually not required in making the diagnosis, as physical findings are
generally sufficient for this purpose.

Hyperlaxity is responsible for many of the clinical
problems in Marfan syndrome, including subluxation of joints, a
predisposition to sprains, and even scoliosis.

Scoliosis is a common reason for which patients are
referred to the orthopaedist. Smaller curves can be managed in a manner
similar to that for idiopathic scoliosis, with bracing considered for
select curves in skeletally immature individuals. Although bracing is
often prescribed, it seems to be less effective than in idiopathic
scoliosis (26). This has led some orthopaedists
to suggest that bracing only delays the need for surgical treatment.
There are no well-controlled studies comparing brace treatment with
observation or any other type of management in these patients.
Therefore, brace treatment remains controversial. Despite this, we
offer brace treatment using the same principles as for idiopathic
scoliosis for children with Marfan syndrome. Curves will often be
relatively short and associated with deformity of vertebrae termed
dysplastic (Fig. 9.3). The spinal deformity is
often associated with kyphosis, especially in the lumbar spine region.
Surgery is considered for rapidly progressive curves in skeletally
immature individuals, or for large progressive curves in skeletally
mature individuals. Surgery in these patients is challenging, with
higher complication rates reported than for idiopathic scoliosis.
Infection, instrumentation fixation failure, pseudarthrosis, or coronal
and sagittal curve decompensation occur in 10% to 20% of patients.
Infection is often associated with a dural tear and decompensation is
associated with extreme correction. Although surgery can be safely
undertaken in most patients, there is a report of a postoperative death
from valvular insufficiency. To avoid such complications, the
cardiopulmonary condition of patients with Marfan syndrome should be
evaluated

preoperatively (27,28,29,30,31,32,33,34).
Computerized tomography (CT) scan to assess bony anatomy, especially of
the pedicles, is quite useful in preoperative planning of hook and
screw placement. Avoidance of extreme correction, extension of the
fusion to vertebrae that are neutral and stable in both planes, and
fusing both primary and secondary curves may prevent curve
decompensation, hardware failure, and pseudarthrosis. We recommend
these techniques in the operative management of this condition. Other
unusual spinal deformities can occur, such as subluxation of vertebrae (35).

Dural ectasia is common in individuals with Marfan
syndrome, and seems to increase in severity with age. Its severity is
not related to the severity of other clinical findings; for instance,
there is no association between aortic dilatation and dural ectasia (36).
Although there is a slightly higher incidence of back pain in patients
with dural ectasia than in those without, a 40% incidence of back pain
in patients with Marfan syndrome without dural ectasia suggests that
dural ectasia itself is not the cause of the pain. One should thus
evaluate patients with Marfan syndrome for other causes of back pain
even in the presence of dural ectasia.

Mild osteopenia is associated with Marfan syndrome; this
may be caused in part by the fibrillin abnormality disrupting the
normal extracellular matrix structure of bone, and in some cases it may
be related to relative physical inactivity. Susceptibility to fracture
does not seem to be a problem, and it is therefore not clear whether
intervention for the decreased bone density is warranted (37,38).
Protrusio acetabula is present in about one-third of patients with
Marfan syndrome. It is not related to bone mineral density and is
usually asymptomatic (39), and thus prophylactic fusion of the triradiate cartilage is probably not warranted.

In patients with Marfan syndrome, cardiovascular failure
can lead to premature death. Indeed, many cases of sudden death during
athletic activities in the young are in individuals with Marfan
syndrome. Despite this, there are no universally accepted criteria for
restricting physical activity in individuals with Marfan syndrome.
Early intervention using β-blockers can reduce the development of
aortic dilatation. Individuals with aortic dilation may also benefit
from earlier cardiac surgical intervention. Lens dislocation requires
ophthalmologic intervention. In Marfan syndrome the lens is dislocated
in a superior direction, whereas in homocystinuria there is an inferior
dislocation. Homocystinuria shares many clinical features with Marfan
syndrome, but is also associated with a coagulation disorder. As such,
it is crucial that an individual suspected of having Marfan syndrome be
evaluated for cardiovascular problems, and that the possibility of
homocystinuria be excluded before the patient undergoes surgery.

The tradition classification of EDS into 11 types (51) has been modified in a way that groups individuals with this disorder into 6 major types (52), based on clinical findings, genetic cause, and inheritance pattern (52) (Table 9.2).
There are at least six additional subtypes of EDS; these are very rare,
often being reported as a single family. Although an understanding of
the genetic cause of the rare types provides important information
about how various proteins contribute to the maintenance of the
mechanical integrity of the soft tissues, the infrequency of their
occurrence makes their incorporation into a general classification
scheme less useful to the clinician.

EDS is caused by mutations in either a collagen gene or
in a gene that produces a protein that processes collagen. The types of
EDS that are caused by a mutation in collagen are inherited in an
autosomal dominant manner, whereas those caused by a protein processing
defect (kyphoscoliotic and dematosparaxis types) are inherited in an
autosomal recessive pattern. Since collagen is the main structural
component of a variety of connective tissues, it is easy to understand
how these mutations cause the associated changes in soft tissue
mechanics (45,53,54).

There are several characteristics that are unique to the individual subtypes (52,55,56).
The hypermobility type, which is characterized by multiple dislocations
of joints, is also associated with a delay in achieving developmental
milestones, perhaps because of the dislocations. Individuals with this
type have the greatest functional disability. The vascular type is
associated with ruptures of vessels or viscera. Such events are rare in
childhood, but by the age of 20, one fourth of those with the condition
will have had some vascular or visceral complication. Teenage boys may
be at a high risk for this during their prepubertal growth spurt (57).
Early death occurs, most commonly because of vascular rupture, with the
median age of survival being less than 50 years. Individuals with the
kyphoscoliosis type often present as “floppy” infants, and this
diagnosis should therefore be considered in such children. Children
with clinical features suggestive of EDS should be referred to a
geneticist. Although molecular diagnosis is possible for some of the
subtypes, these are usually not needed for making the diagnosis. There
are no universally accepted criteria for restricting participation in
physical activity in patients with EDS, so recommendations to limit
activity should be made on an individual basis.

Subluxations and recurrent dislocations of joints are
common occurrences in the various subtypes. The chronic pain that such
individuals complain of is often attributed to these subluxations. The
management of the subluxations is problematic, and a multidisciplinary
effort, including pharmacologic and physical therapeutic approaches, is
often required. Since the matrix components that provide the mechanical
properties to the soft tissues are defective, surgical approaches
focusing on ligaments and tendons (e.g., soft tissue procedures around
the shoulder) have a low success rate. Procedures that involve surgery
to the bones to better contain the joints have a higher success rate. A
variety of such operations are reported, such as osteotomies, which
change the direction and location of insertion of tendons or capsules
or that provide a larger joint area (tibial tubercle transfer
operations for patellar dislocations, and femoral and pelvic
osteotomies for hip subluxation). In particularly problematic cases, it
may be necessary to place a bone graft to limit motion and prevent
dislocation (e.g., a posteriorly placed graft at the elbow).
Arthrodesis may be required as a last resort in those cases that remain
symptomatic despite other managements (58,59,60).

Scoliosis is common in EDS, and is usually managed using
the same principles as those for idiopathic scoliosis, despite a lack
of studies showing this management approach to be efficacious. Surgical
management can be

problematic in the vascular type, in which vessel ruptures can occur during surgery (61).
It is important not to place undue stretch on vessels during surgery,
and it is probably safest to have a vascular surgeon available in case
a major disruption is encountered. Cardiac valve problems can occur in
EDS, so patients should have a cardiac evaluation before undergoing
surgery. Low bone density is identified in EDS; however, when one
corrects for the activity level of these patients, the bone density may
not be so abnormal (62). Pharmacologic treatment for low bone density should be considered only in rare instances.

Café-au-lait spots are discrete, tan spots (Fig. 9.5).
In patients with NF these spots often appear after 1 year of age, and
then they steadily increase in number and size. The spots have a smooth
edge, often described as similar to the coast of California, as opposed
to the ragged edge of spots associated with fibrous dysplasia, which
are described as similar to the coast of Maine. The spots vary greatly
in number, shape, and size, and six lesions greater than 1 cm in size
are required for the diagnostic criteria. Axillary and inguinal
freckling are common and serve as good diagnostic markers, because such
freckling is exceptionally rare except in people with NF.
Hyperpigmented nevi are dark brown areas that are sensitive to the
touch; they typically overlie a deeper plexiform neurofibroma.

The two types of neurofibroma are different in their anatomic configuration and clinical morbidity. The most

common is the cutaneous neurofibroma, composed of benign Schwann cells and fibrous connective tissue (Fig. 9.6).
This type of neurofibroma may occur anywhere, but is usually just below
the skin. These neurofibromas may not be detectable until 10 years of
age, and with puberty there is a rapid increase in their number. When
many are grouped together on the skin, it is known as a fibroma molluscum.
Plexiform neurofibromas are usually present at birth and are highly
infiltrative in the surrounding tissues. The overlying skin is often
darkly pigmented. They are highly vascular and lead to limb giantism,
facial disfigurement, and invasion of the neuroaxis (Figs. 9.7 and 9.8).

There are many skeletal manifestations, but the presence
of an unusual scoliosis, overgrowth of a part, or a congenital
pseudarthrosis lesion seen on radiographs should alert the physician to
consider a diagnosis of NF (65). There are a
variety of anomalies of bone observed in radiographic images, ranging
from a scalloping of the cortex, to cystic lesions in long bones that
look much like nonossifying fibromas, to permeative bone destruction (Fig. 9.9). These radiographic findings may mimic benign or malignant bone lesions (66,67,68).
Radiographs of the pelvis usually show various degrees of coxa valga,
and in nearly 20% of patients there is radiographic evidence of
protrusio acetabuli (69,70).

Lisch nodules are hamartomas of the iris. These nodules
are present in 50% of all 5-year-olds with NF1, and in all adults with
NF1. It is unusual for Lisch nodules to be present in individuals who
do not have NF1, and so the detection of these nodules can aid in
making this diagnosis. However, it may be difficult to detect these
lesions, and patients should be sent to an experienced ophthalmologist
for this diagnosis. The lesions do not cause any visual disturbances.
Once the diagnosis is established, further ophthalmologic evaluation is
not necessary (71,72).

NF is the most common single-gene disorder in humans, affecting 1 in 3000 newborns (73,74,75).
NF1 is an autosomal dominant disorder with 100% penetrance, but
one-half of cases are sporadic mutations and are associated with an
older-than-average paternal age. The most well-known patient who was
presumed to have had NF, Joseph Merrick, also called the Elephant Man,
probably did not have this condition; his clinical profile better fits
Proteus syndrome (76). The NF1 gene is located on chromosome 17 (77). Its protein product, neurofibromin, acts as a tumor suppressor (78). There are also other potential genes located in introns within the NF1 gene, whose functional significance is unclear.

Neurofibromin has similarity to the G-protein family of
signal transduction proteins. These proteins convey messages from cell
surface receptors to cytoplasmic effectors. Neurofibromin plays such a
role in the Ras signaling system, which is involved in the control of
cell growth (79). Mutations in the NF1
gene cause a disruption in its normal regulatory function of Ras
signaling. This gives the affected cells an abnormal growth pattern.
Neurofibromin is expressed at higher levels in the neural crest during
development. Cells from the neural crest migrate to become pigmented
cells of the skin, parts of the brain, spinal cord, peripheral nerves,
and adrenals, thus explaining the common sites of abnormalities in the
disorder. The gene defect gives a clue to potential novel therapies,
because pharmacologic agents that block Ras signaling could be used to
treat the disorder. Disruption of the normal Ras signaling cascade is
probably responsible for the malignant potential of this disorder. Only
one of the two copies of the NF1 gene is
mutated in affected patients; however, tumors from such individuals
have been found to have only the mutated gene because of loss of the
normal copy (80,81,82,83).
Farnestyl transferase inhibitors block the downstream effects of Ras
signaling activation and thus have the potential to be used in the
treatment of some of the more severe

manifestations of NF. There are several ongoing early-phase trials of such drugs (84,85).

Although patients with other forms of NF rarely present
to an orthopaedist, one should be aware of these types because
musculoskeletal malformations are occasionally present. Patients with
NF2 present with acoustic neuromas, central nervous system tumors, and
rare peripheral manifestations. There are usually fewer than six
café-au-lait spots, and no peripheral neurofibromata. These patients
are very unlikely to present with an orthopaedic deformity. There are
two much less common types of NF, type three and type four (NF3 and
NF4), in which patients are more likely to develop a problem requiring
orthopaedic intervention. Individuals with NF3 present with some of the
characteristics of NF1, but also have acoustic neuromas, which are
characteristic of NF2. These individuals often have spinal deformity,
especially in the cervical region. NF4 presents with the same clinical
findings as NF1, except that one of the cardinal features of NF1,
namely, Lisch nodules of the iris, is absent (63,64).
It is important to distinguish these types from NF1, because they are
probably caused by mutations in a gene different from the one that
causes NF1 (this has already been demonstrated in NF2), and will
therefore not be diagnosed by DNA testing for NF1.

The common orthopaedic manifestations of NF, including
scoliosis, overgrowth of the limbs, pseudarthrosis, and radiographic
appearances of lesions, enable the initial diagnosis to be made if the
syndrome is kept in mind. Patients with NF often exhibit overgrowth,
ranging from a single digit to an entire limb and from mild anisomelia
to massive giantism. As such, the possibility of NF should be
considered in a child with focal giantism, such as macrodactyly. When
NF is compared with the more symmetric idiopathic hemihypertrophy,
there is disproportional overgrowth involving the skin and subcutaneous
tissue more than the bone (Fig. 9.8).

Scoliosis is common, and curves tend to fall into two
categories: a dystrophic curve and an idiopathic curve. Most curves in
NF resemble idiopathic scoliosis curves.

Their
relation to NF is not understood, and their precise incidence is still
being debated. These curves can be managed like any other idiopathic
curve.

The dystrophic scoliotic curve is a short, sharp, single thoracic curve typically involving four to six segments (Fig. 9.10) (69,86,87,88,89,90,91,92,93).
It is associated with deformity of the ribs and vertebrae. The onset is
early in childhood, and it is relentlessly progressive. Curves that
initially appear to be idiopathic in children under age 7 have almost a
70% chance of becoming dystrophic over time, although there may be
subtle clues, for example, mild rib penciling (thinning of the ribs in
a shape similar to a pencil point near the vertebrae), suggesting that
the curve is actually dystrophic. The most important risk factors for
progression are an early age of onset, a high Cobb angle, and an apical
vertebra that is severely rotated, scalloped (concave loss of bone),
and located in the middle-to-lower thoracic area (90).
The combination of curve progression and vertebral malformation mimics
congenital scoliosis in appearance and behavior. Dystrophic curves are
refractive to brace treatment. Sagittal plane deformities may occur,
including an angular kyphosis (i.e., gibbus) and a scoliosis that has
so much rotation that curve progression is more obvious on the lateral
than on the anteroposterior radiograph (90). In
those with angular kyphosis, there is a risk of paraplegia. Dystrophic
curves are difficult to stabilize, and it is best to intervene with
early surgery involving both anterior and posterior fusion (90,94,95,96).
Kyphotic deformities are often the most difficult to manage surgically,
and strut grafts across the kyphosis anteriorly may be necessary. In
rare severe cases, the spine can even seem to be “dislocated” because
of the kyphosis and scoliosis. In cases with extremely severe
deformity, halo-femoral or halo-gravity traction may be necessary to
safely straighten the spine to a more acceptable deformity without
producing neurologic sequelae. Other reported techniques include
inserting a bone graft without instrumentation and then gradually
straightening the curve using a cast postoperatively (97).
In rare severe cases in which there is a vertebral “dislocation” one
can use instrumentation to achieve an overall alignment of the back,
while leaving the vertebrae “dislocated” (98). Unusual complications have been reported in the management of such dystrophic curves, such as a rib head

migrating into the neural canal resulting in spinal cord compromise (99).

There can be several vertebral abnormalities evident on
radiographs. These include scalloping of the posterior body,
enlargement of the neural foramina, and defective pedicles,
occasionally with a completely dislocated vertebral body (100,101,102,103,104).
Such findings may mean that there is a dumbbell-shaped neurofibroma in
the spinal canal, extending out through a neural foramina. The dura in
NF patients behaves like the dura in patients with a connective tissue
disorder, and dural ectasia is common, with pseudomeningoceles
protruding through the neural foramina. Unlike neurofibroma, dural
ectasia is an outpouching of the dura, without an underlying tumor or
overgrowth of spinal elements (Fig. 9.11) (105,106,107,108). The incidence of anterolateral mening-oceles was underestimated until asymptomatic patients were screened with MRI (65,109).
The erosion of the pedicles may lead to spinal instability, especially
in the cervical spine. In rare cases, this can even lead to dislocation
of the spine (110,111).
MRI and CT scans are helpful preoperatively in delineating the presence
of defective vertebrae or dural abnormalities, and may assist in
choosing the levels on which to place instrumentation.

Pseudarthrosis of a long bone is typically associated with NF (88). It usually affects the tibia, with a characteristic anterolateral bow that is obvious in infancy (Fig. 9.12) (112,113).
Fracture usually follows, with spontaneous union being rare and
surgical union presenting a challenge. An anterolateral bowed tibia is
routinely managed with a total-contact orthosis to prevent fracture,
although there are no well-designed studies showing that this is indeed
effective. Intramedullary rod fixation seems to offer the best results
for the initial management of a pseudarthrosis. Recent studies have
shown the importance of achieving neutral tibial alignment in the
healing of a tibial pseudarthrosis. The presence of an intact fibula is
associated with a lower healing rate, perhaps because of associated
tibial malalignment (114). The cause of the
pseudarthrosis is not known; however, neurofibromas have not been
identified at the pseudarthrosis site. The pseudarthrosis process may
affect the ulna, radius, femur, or clavicle (115,116,117,118,119,120,121).
In each of these locations, there is a course similar to that in the
tibia, with bone loss and difficulty in achieving union (Fig. 9.13). Not all pseudarthroses of the forearm require treatment (122), but if they are symptomatic, the available options include proximal and distal synostosis to produce a single-bone

forearm, the use of a vascularized fibula graft, or resection of the
pseudarthrosis with shortening of the forearm and internal fixation (123).

There are a variety of benign and malignant neoplastic
processes that affect individuals with NF1. Most neurofibromas do not
require treatment, but symptomatic lesions may require excision.
Plexiform neurofibromas that become symptomatic are very difficult to
manage. Their vascularity and infiltrative nature make complete
extirpation almost impossible, with a substantial risk of
uncontrollable hemorrhage and neurologic deficit. Although speculative,
the use of angiogenesis inhibitors, such as interferon, or some
experimental agents that modulate the effect of the causative gene
mutation, such as farnesyl transferase inhibitors, may be beneficial (124,125).

The exact incidence of malignancy in NF is controversial, with reported rates ranging from under 1% to over 20% (126,127,128,129,130).
The most common tumor location is in the central nervous system, with
lesions such as optic nerve glioma, acoustic neuroma, and astrocytoma (131).
There is a risk of malignant degeneration of a neurofibroma to a
neurofibrosarcoma. This process can occur in a central or peripheral
neurofibroma (132,133,134,135).
It can be quite difficult to distinguish a malignant lesion from a
benign one. CT scans show areas of low-enhancing density in
neurofibrosarcomas (136), but there are no
studies confirming the sensitivity and specificity of this finding.
Similar patterns can also be visualized using MRI. Routine surveillance
for sarcomatous change is impossible because of the large number of
neurofibromas. Lesions that increase in size or develop new
characteristics should be investigated. There is a propensity for
children with neurofibroma to develop other malignancies, such as Wilm
tumors or rhabdomyosarcomas.

Hypertension as a result of renal artery stenosis or
pheochromocytoma is reported regularly, as is a curious type of
metabolic bone disease similar to hypophosphatemic osteomalacia (137,138). Hypertension is a major

risk factor for early death (130). Precocious puberty may occur because of an intracranial lesion (139).
Affected children are short, but tend to have large heads.
Approximately 50% have an intellectual handicap. Although the mean IQ
is low, the range of IQ is quite wide (140).
More than the low IQ, it is the difficulty in concentrating (which is
common in this condition) that may interfere with the learning process (141). The concentration problems can sometimes be managed pharmacologically.

MPS type I is the clinical prototype. It is
characterized by a deficiency of L-iduronidase, the enzyme that
degrades dermatan sulfate and heparan sulfate. The Hurler and Scheie
forms represent the severe and mild ends of the clinical spectrum in
MPS I. Children with the Hurler form have progressive mental
retardation, severe, multiple skeletal

deformities,
and considerable organ and soft tissue deformities, and die before the
age of 10 years. The Scheie form is characterized by stiffness of the
joints and corneal clouding, but no mental retardation; the diagnosis
is usually made at approximately 15 years of age, and the patient has a
normal life expectancy. Many patients with MPS I fall in the middle of
this clinical spectrum. The clinical variation is determined by the
location and type of mutation that occurs along the gene for
L-iduronidase (410,411).

Marrow transplantation is used in the treatment of the
more severe forms (Hurler syndrome). However, the results on the bones
are variable (412), with most children still
developing the typical skeletal phenotypic features despite undergoing
successful bone marrow transplant (413,414). This may be due to the poor penetration of the enzyme derived from the transplanted leukocytes to the osseous cells (412).
Initial studies suggested an improvement in most of the nonosseous
manifestations of the disease with marrow transplant. More recent
longer-term studies cast doubt on the long-term effectiveness of marrow
transplantation (415). Despite these
disappointing longer-term results, marrow transplant may provide
short-term improvement, especially in the nonosseous manifestations.
The musculoskeletal deformities that persist after marrow transplant
still require treatment.

Malalignment of the limbs can occur, and epiphyseal stapling, or osteotomies, may be necessary for genu valgum (416).
Approximately one-fourth of the patients have an abnormality of the
upper cervical spine. Odontoid hypoplasia and a soft tissue mass in the
canal can be managed like those in Morquio syndrome (described in the
following text). The accumulation of degradation products in closed
anatomic spaces, such as the carpal tunnel, causes “triggering” of the
fingers and carpal tunnel syndrome. These can be managed operatively (417,418).

Between 1929 and 1959, there was a miscellany of skeletal diseases described as Morquio syndrome,
including several types of spondyloepiphyseal dysplasia. Morquio
syndrome is an autosomal recessive disorder with an incidence of 3 per
1,000,000 of the population. Three types of Morquio syndrome are
classified as subtypes of MPS IV. All are caused by enzyme defects
involved in the degradation of keratan sulfate (408,409,410).

Patients with severe classic MPS IVA are short-trunked
dwarfs, although they appear normal at birth. They develop corneal
opacities. The bone dysplasia is radiographically obvious, and the
final height is less than 125 cm (50 in.). Patients have abnormal
dentition. The deficient enzyme is N-acetylgalactosamine-6-sulfate sulfatase, and the chromosomal defect occurs at 16q24.3 (419).
Patients with intermediate MPS IVB have the same but milder phenotypes
as those with type IVA. They are taller, with final heights greater
than 125 cm (50 in.), and they have normal dentition. Here the enzyme
defect is β-D-galactosidase. Patients with mild MPS IVC have very mild
clinical manifestations.

The three forms of Morquio MPS IV can be distinguished
by the severity of symptoms and the patient’s age at detection. All
these patients are normal at birth. For patients with the severe type
IVA, the diagnosis is made between 1 and 3 years of age; those with the
mild type IVC are diagnosed as teens; and those with the intermediate
form (type IVB) are diagnosed somewhere in the middle of this age
range. The three forms may also be separated by the severity of the
radiographic changes.

Intelligence is normal in patients of all of the MPS IV
types, and only rarely are the facial features coarsened. Similarly,
all are short-trunked dwarfs with ligamentous laxity; the laxity is
rather profound in MPS IVA. The degree of genu valgus is significant,
aggravated by the lax ligaments (420,421,422,423).

Management of the knee proves difficult because of the
osseous malalignment and the lax ligaments. Although it is observed
that the fingers and joints are becoming stiff, the medial and lateral
instability of the knee remains. Realignment osteotomies can restore
plumb alignment, but braces may be needed to control the instability
during ambulation. The prophylactic use of braces to prevent initial
valgus or recurrent deformity

after surgery has not been effective (420,421,422,423).
The hips and knees develop early arthritis. The hips show a progressive
acetabular dysplasia. Radiographs may show a small femoral ossific
nucleus, but an MRI or arthrogram will show a much larger cartilagenous
femoral head. The femoral capital epiphyses are initially advanced for
the patient’s age, but between 4 and 9 years of age the femoral heads
grow smaller, then disappear altogether (Fig. 9.36).
The pathophysiology of the progressive hip disease is not completely
understood, and neither medication nor surgery has been shown to
improve the prognosis (420,421,422,423).

Odontoid hypoplasia or aplasia is universal, with resultant C1–C2 instability (422,423,424,425)W (Fig. 9.36). There is a soft tissue mass in the spinal canal, contributing to

cord compression (425,426).
This soft tissue mass can make the space available for the cord smaller
than one would expect on the basis of radiographs alone. Neurologic
function, especially upper-extremity strength and tone, is probably
more important than measuring distances on dynamic cervical spine
films. The upper- and lower-extremity findings are often of flaccidity
rather than spasticity. The onset of the myelopathy can occur as early
as the first decade of life, progressing as the soft tissue
hypertrophies, with the C1–C2 instabilities aggravating the situation.
Sudden deaths of patients with Morquio disease have been reported, and
they are typically attributed to the C1–C2 subluxation. C1–C2 fusion
before the onset of symptoms is controversial, but promoted by some (425,427). Others think the best surgery is occipital cervical fusion because it reduces the anterior soft tissue mass (426,427).
There are no comparative studies evaluating the outcomes of each of the
different management approaches. On the basis of the available
information, it is reasonable to obtain MRI studies on symptomatic
individuals, or on those with radiographic evidence of instability.
C1–C2 fusions are recommended for asymptomatic individuals with MRI
evidence of cord compression. Symptomatic individuals should have
fusions throughout the region of instability and cord compression.
Although decompression is usually performed along with the fusion,
anecdotal evidence suggests that fusion alone may be sufficient,
resulting in the soft tissue mass decreasing in size.

Elsewhere in the spine, the vertebrae show a progressive
platyspondylia with a thoracic kyphosis. Progressive deformity should
be surgically stabilized. Anterior instrumentation is an effective
surgical technique (428). Despite these
problems, many patients with Morquio disease live for decades.
Cardiorespiratory disease is common, but the problems at the upper
cervical spine account for most disabilities.

Arthrogryposis multiplex congenita is the best-known of the multiple congenital contracture syndromes (451,452). Although attempts have been made to change the name arthrogryposis multiplex congenita to multiple congenital contractures or amyoplasia (AMP), the popularity of arthrogryposis remains.

The etiology of arthrogryposis multiplex congenita is
unknown. It was initially described in 1841 by Adolf Wilhelm Otto, who
referred to his patient as a “human wonder with curved limbs” (453).
The disorder is sporadic, with affected individuals having reproduced
only normal children. Classic arthrogryposis can affect only one of
identical twins (454,455).
The development of arthrogryposis may be influenced by an adverse
intrauterine factor or the twinning process itself. Teratogens have
been suggested, but none are proven, despite the multiple animal models
that lend support to that theory (452,456,457,458,459).
Some mothers of children with arthrogryposis have serum antibodies that
inhibit fetal acetylcholine receptor function. One possibility is that
maternal antibodies to these fetal antigens cause the disorder (460).

Histologic analysis discloses a small muscle mass with
fibrosis and fat between the muscle fibers. Myopathic and neuropathic
features are often found in the same muscle biopsy specimen. The
periarticular soft tissue structures are fibrotic and, in essence,
there is a fibrous ankylosis. The number of anterior horn cells in the
spinal cord is decreased, without an increase in the number of
microglial cells (461,462,463).
The pattern of motor neuron loss in specific spinal cord segments
correlates with the peripheral deformities and the affected muscles,
suggesting that a primary central nervous system disorder plays an
important role in causing this condition (464).

Clinical examination remains the best way to establish a diagnosis. The limbs are striking in appearance and position (Fig. 9.40).
They are featureless and tubular. Normal skin creases are lacking, but
there may be deep dimples over the joints. Muscle mass is reduced,
although in infancy there is often abundant subcutaneous tissue.
Typically, the shoulders are adducted and internally rotated, the elbow
more often extended than flexed, and the wrist flexed severely, with
ulnar deviation. The fingers are flexed, clutching the thumb. In the
lower extremities, the hips are flexed, abducted, and externally
rotated; the knees are typically in extension, although flexion is
possible; clubfeet are the rule. Motion of the joints is restricted.
The condition is pain-free, with a firm, inelastic block to movement
beyond a very limited range. In two-thirds of the patients, all four
limbs are affected equally, but in one-third, lower-limb deformities
predominate. Only on rare occasions do the upper extremities
predominate. Deformities tend to be more severe and more rigid
distally. The hips may be dislocated unilaterally or bilaterally.

The viscera are usually spared from malformations,
although gastroschisis has been reported. As a consequence of the
general muscle weakness, there is a 15% incidence of inguinal hernia.
Major feeding difficulties, caused by a stiff jaw and an immobile
tongue, are frequently encountered in infancy, and lead to respiratory
infections and failure to thrive (465). The
face is not particularly dysmorphic. A few subtle features, such as a
small jaw, narrowing of the face and, occasionally, limited upward gaze
(secondary to ocular muscle involvement). A frontal midline hemangioma
may help with the diagnosis (Fig. 9.40).

Radiographs reveal that the joints are normal, and that
changes are adaptive and acquired over time as a consequence of their
fixed position (Fig. 9.41). There is evidence
of a loss of subcutaneous fat and tissue. Electromyograms and muscle
biopsies are of questionable diagnostic value. They have been used to
separate patients with primarily neuropathic changes from those with
myopathic changes, but the clinical implications of such distinctions
are not clear. A diagnosis of arthrogryposis can be suspected when
prenatal ultrasound detects an absence of fetal movement, especially if
seen in combination with polyhydramnios (456).

Despite every large medical center having treated
patients with arthrogryposis, the natural history and long-term
outcomes are not well known (466,467).
Some contractures seem to worsen with age, and the joints become
stiffer. No new joints become involved. At least 25% of affected
patients are nonambulatory, and many others are limited household
walkers (468). As a rule, those with
arthrogryposis who are very weak as infants stay weak, and those who
appear stronger as infants stay strong. The dependency of adults seems
to be related to education and coping skills more than to the magnitude
of contractures of the joints.

The essential features of Larsen syndrome are multiple
congenital dislocations of large joints, a characteristic flat face,
and ligamentous laxity (505) (Fig. 9.42).
The cause of the facial flattening is unclear, but it is especially
noticeable when observed in profile, and is associated with some
hypertelorism and a broad forehead. Dislocation of multiple joints
appears in a characteristic pattern that includes bilateral dislocated
knees, with the tibia anterior on the femur, bilateral dislocated hips,
bilateral dislocated elbows, and bilateral clubfeet (506,507,508,509,510).
The physician should think of this syndrome whenever dislocated knees
are detected. The ligaments are lax or entirely absent. The ligamentous
laxity is often so substantial that Larsen syndrome may be confused
with EDS.

Radiographs show that the knees are dislocated, with the tibia anterior to the femur (508). Arthrograms show a small or absent suprapatellar pouch, absent cruciate ligaments, and a misaligned patella (Fig. 9.43).
The elbows have complex radial–humeral, ulnar–humeral, and radial–ulnar
dislocations. Radial–ulnar synostosis is common and usually associated
with ulnar–humeral dislocation (Fig. 9.44B). A
spheroid ossicle frequently occurs anterior to the elbow joint; its
origin is unknown. There are more carpal centers than are normal (Fig. 9.44A), and extra ossification centers in the foot, with a curious double ossification pattern of the calcaneus (Fig. 9.44C).
This double ossification pattern can help confirm the diagnosis in
cases in which the diagnosis is not clear. Abnormal cervical spine
segmentation, with instability, is typical, as is kyphosis, a
complication often associated with myelopathy. Some cases are inherited
in an autosomal dominant manner, and this aids in the diagnosis.

Both autosomal dominant and recessive inheritances are reported in Larsen syndrome, although many cases are sporadic (511,512,513). Some autosomal dominant cases are caused by mutations in the gene encoding filamin B (514).
This is an intracellular protein that serves as scaffolding on which
signaling and protein trafficking pathways are organized. It is
expressed in the growth-plate and vertebrae, and

as
such, the mutation likely acts to disrupt normal patterning and
development of the joints and vertebral bodies, resulting in the
typical phenotypic features. There are cases in which only one side of
the body has a Larsen syndrome phenotype, suggesting that some cases
are due to somatic, or mosaic, mutations (515).

The large numbers of deformities of the lower
extremities require treatment in order to achieve stable, located
joints. Knee stability is necessary to achieve ambulation. Reduction
almost always requires surgery. The knee may remain unstable after
reduction because of the lack of major stabilizing ligaments, such as
the anterior cruciate ligament. Long-term orthoses are often needed.
Successful anterior cruciate ligament reconstruction has not been
reported. The knee is usually reduced before the hips, although
simultaneous procedures are possible (508,516).
Although most knees do not respond to attempts at manipulation and cast
correction, traditionally an initial trial of cast treatment is
attempted. Too-vigorous manipulations result in distal femoral
metaphyseal–physeal fractures. Because manipulation has not been found
to be helpful for true dislocations, we believe that it can be
abandoned once a dislocation is confirmed. Surgery may be undertaken as
early as 3 to 4 months of age. Restoration of the range of motion must
be cautious (gaining full extension is often a problem), and a flexion
splint or brace may be required after operative reduction to guard
against redislocation.

The hips are dislocated, often despite a rather
normal-appearing acetabulum. There is a sense of a good range of
motion, although the hip may prove to be irreducible (510).
The evolution of hip management in Larsen syndrome mirrors that in
arthrogryposis multiplex congenita, and there is a trend toward earlier
treatment. The relative rarity of this syndrome, however, accounts for
the lack of good comparative data on how best to manage the hip
dislocations. Reduction of the hip is associated with a high
redislocation rate and revision surgery (508,509,510).
For this reason, some specialists advocate either leaving bilateral
dislocated hips alone, or waiting until after 1 year of age and
performing femoral and pelvic osteotomies, along with the open
reduction. However, we prefer an approach similar to that in
arthrogryposis, with early surgical relocation (usually through a
medial approach). Because the knees are hyperextended when dislocated
and cast in a flexed position after surgical relocation, both knees and
hips can be operated upon at the same time. Secondary osteotomy of the
pelvis and femur can be performed later, if necessary.

The clubfeet can be managed in a cast until the knee deformity is corrected. Some feet can be corrected with

serial casting, but long-term results suggest less residual deformity when the foot is treated surgically (508).
The foot may need to be braced to control ankle instability. Despite
the dislocations of the elbow or shoulder, the arms remain functional
and rarely require treatment. Crutches or walkers can be used despite
the dislocations.

The major concern involving the spine is structural abnormalities of the cervical vertebrae (517,518).
This manifestation may occur more frequently than previously
recognized, and children should have cervical spine films taken in the
first year of life to identify this deformity. Kyphosis is often due to
hypoplasia of the vertebral bodies. A combination of cervical kyphosis
and forward subluxation may result in quadriplegia and death. Posterior
stabilization early (within the first 18 months of life) may prevent
the significant problems associated with treatment after myelopathy has
occurred and allow for correction of a kyphotic deformity with growth (519).

Anesthesia complications are common. The mobile
infolding arytenoid cartilage creates airway difficulties. The
associated tracheomalacia can be especially problematic in the newborn,
and may delay surgery for the hips and knees (520).
The anesthesiologist should be aware of possible cervical spine
instability, and a preoperative lateral radiograph is recommended.

The children have normal intelligence. The prognosis is
generally good with aggressive orthopaedic treatment if the child
survives the first year of life. The mortality figures for the first
year may be as high as 40%. During the neonatal period, the
cartilage-supporting structure of the larynx and trachea is soft, and
there may be alarming elasticity of the thoracic cage at the
costochondral junction, leading to respiratory failure and death.
Cervical spine problems may also contribute to early mortality.
Congenital cardiac septal defects, elongation of the aorta, and
acquired lesions of the mitral valve and aorta, similar to those found
in Marfan syndrome, further complicate medical and anesthesia
management (521,522).

Children with distal arthrogryposis have characteristic
fixed hand contractures and foot deformities, but the major large
joints of the arms and legs are spared (523,524,525).
Because different craniofacial abnormalities are often associated with
distal arthrogryposis, the condition has been categorized as several
eponymic syndromes (e.g., Gordon syndrome), a situation that leads to
confusion (526). The cardinal features of
distal arthrogryposis are the hand deformity with ulnar deviation of
the fingers at the metacarpophalangeal (MCP) joint, flexion deformities
at the proximal interphalangeal and MCP joints, and a cup-like palm
with a single palmar crease (Fig. 9.45). The thumb is flexed and adducted, with a web at its base (527).
Distal arthrogryposis is common, and is sometimes incorrectly called
multiple camptodactyly. The inheritance pattern of distal
arthrogryposis is autosomal dominant, but there may be considerable
variation in families, and this can lead to missing the diagnosis (526,527,528,529).
Distal arthrogryposis is divided into type I and type II on the basis
of the absence or presence of facial findings, respectively.

Some cases of distal arthrogryposis type I are caused by mutations in the TPM2 gene, which encodes β-tropomyosin, a protein important in fast-twitch muscle fibers (530).
Type II distal arthrogryposis (Freeman-Sheldon syndrome) is caused by
mutations in an isoform of troponin I that is specific to the
troponin-tropomyosin complex of fast-twitch myofibers (530).
Both these mutations result in abnormal activity of fast-twitch muscle
fibers, suggesting that dysregulation of these muscle fibers is the
common pathophysiologic cause of distal arthrogryposis. Because there
are a variety of subtypes of distal arthrogryposis, it is likely that a
number of causative genes will be identified, and perhaps all of these
will play a role in the dysregulation of fast-twitch muscle fibers.

Although the hand deformity is characteristic and
constant, the feet may be clubbed, have stiff metatarsus adductus, and
have a vertical talus. The major joints in the upper and lower
extremities are otherwise normal, although a minor knee-flexion
deformity may be found. Intelligence is normal. The associated
craniofacial anomalies are cleft lip or cleft palate and, in such
patients, the syndrome of distal arthrogryposis may have an eponymous
name, such as Gordon syndrome (531,532).
Radiographs show normal bony architecture, and only with persistence of
deformities in the hands and feet are articular changes detected.

This
syndrome can be diagnosed prenatally in the fetus by detecting an
unchanged position and lack of motion of the hands in contrast to the
normal activity of the large uninvolved joints (533).

Overall, children with distal arthrogryposis have good
function. The hands function well because the shoulders, elbows, and
wrists are normal. Thumb surgery to lengthen the flexor pollicis longus
and rebalance the extensor is the most common surgery (534).
The feet more frequently require surgery. Some clubfeet can be
corrected with manipulation and serial casts. Most are treated with
circumferential releases. The outcome of treatment of clubfoot is
better in this syndrome than in other arthrogrypotic clubfeet.

Freeman-Sheldon syndrome is sometimes called distal arthrogryposis type II
because the hand and foot deformities are similar to those of distal
arthrogryposis. It is recognized by its most characteristic feature, a
“whistling face” (Fig. 9.46). The original name, craniocarpotarsal dystrophy, is misleading because it does not involve the cranium (535,536). This syndrome is usually sporadic, although there is evidence of autosomal dominant and autosomal recessive inheritance (537,538,539).
The eyes are deeply set. The cheeks are fleshy, and pursed lips
simulate whistling. There is a small mouth and a curious H-shaped
dimple in the chin.

Scoliosis was not initially recognized as a common
feature, but it affects more than one-half of the patients. The onset
is in the first decade. It is often severe, with a left thoracic
pattern reported regularly. The vertebrae are normally shaped. Although
the scoliosis can be managed as in idiopathic scoliosis, the curves are
more rigid and may not respond well to brace treatment (538,540).

The hands demonstrate the classic distal arthrogryposis pattern described earlier (538,540,541).
There are other contractures, including flexion deformities of the
elbow and knee, decreased range of motion of the shoulder, decreased
range of motion of the neck, and dislocated hips (542).
Operative management principles for the upper extremity are similar to
those in distal arthrogryposis. The hands are treated with physical and
occupational therapy, but there is less improvement than is seen in the
other distal arthrogryposis syndromes (543). Most of the other associated contractures can be treated like those in the other arthrogrypotic syndromes.

Clubfoot is the most common foot deformity, with vertical talus being the next most common (Fig. 9.47) (538,540,541). The clubfoot and vertical talus deformities are resistant to nonoperative measures.

During infancy, dysphagia and aspiration lead to failure
to thrive, and even to death. Surgery to permit adequate mouth opening
for feeding may be necessary (544). Children
who survive the neonatal period do well and have normal intelligence.
Anesthesia complications are common; some are the result of
abnormalities related to the laryngeal cartilages (544,545,546,547).
The cause is unknown, but the buccinator muscle is hypoplastic, and
electromyograms and muscle biopsies are identical to the peripheral
muscle studies in classic arthrogryposis multiplex congenita (548), suggesting some similarity in pathophysiology.

Pterygium comes from a Greek
word meaning “little wing.” A pterygium is a web. It can be seen as an
isolated malformation in some syndromes, such as the pterygium colli in
the neck of patients with Klippel-Feil syndrome.

There are two clinically important pterygia syndromes: multiple pterygium syndrome and popliteal pterygia syndrome (549). Several pterygium syndromes are lethal, with the affected patients not surviving the fetal or the newborn period (550,551).
The web syndromes are separated genetically as autosomal recessive
(i.e., lethal pterygium syndrome and multiple pterygium) and autosomal
dominant (i.e., popliteal pterygium) (552).
However, they often overlap. Lethal pterygium syndrome may be diagnosed
prenatally by detecting hydrops and cystic hygroma colli (553).

Both popliteal pterygium syndrome and van der Woude
syndrome are caused by mutations in the gene encoding interferon
regulatory factor-6 (554). Van der Woude syndrome is a dominantly inherited developmental disorder

characterized by pits or sinuses of the lower lip, and cleft lip or
cleft palate. It is unclear how a mutation in this interferon
regulatory factor causes these seemingly dissimilar syndromes.

Multiple pterygia syndrome (i.e., Escobar syndrome) is
characterized by a web across every flexion crease in the extremities,
most prominently across the popliteal space, the elbow, and in the
axilla (555,556) (Fig. 9.48).
There also are webs across the neck laterally and anteriorly from
sternum to chin, drawing the facial features down. The fingers are
webbed. The webs can be obvious, but if they are not, the affected
children can look very much like those with arthrogryposis multiplex
congenita. The two features that differentiate this syndrome from
classic arthrogryposis are vertical talus and congenital spine
deformity. The vertical talus is fairly constant in multiple pterygium
syndrome and can be managed only by surgery. Circumferential release
and prolonged protection, as in managing any arthrogrypotic foot
deformity, are necessary. The spine deformity is significant, with
multiple segmentation abnormalities and lordoscoliosis (557) (Figs. 9.49 and 9.50).
The lordoscoliosis may be substantial enough to interfere with trunk
and chest growth, leading to respiratory death during the first or
second year of life (Fig. 9.50). Mobility
depends much on the magnitude of the lower-extremity webs and the
residual motion of the joints, with many patients limited to
wheelchairs for locomotion. The children have normal intelligence, and
efforts should be maximized to enable them to function independently.
Surgery is rarely needed for the upper extremities.

Popliteal pterygium syndrome (i.e.,
fascial-genital-popliteal syndrome) has recognizable characteristics in
the face, the genitals, and the knee (558,559,560,561,562). The features include a cleft lip and palate, lip pits, and intraoral adhesions (563,564). A fibrous band crosses the perineum and distorts the genitalia (565). A popliteal web is usually present bilaterally (562).
It runs from ischium to calcaneus, resulting in a severe knee-flexion
deformity. Tibia hypoplasia may be associated. Within the popliteal web
is a superficial fibrous band, over which lies a tent of muscle running
from the os calcis to the ischium, and is known in the older literature
as a “calcaneoischiadicus muscle.” The popliteal artery and vein are
usually deep, but the sciatic nerve is superficial in the web, just
underneath the fibrous band (Fig. 9.51). There is a distinctive foot abnormality in this syndrome: a bifid great toenail and syndactyly of the lesser toes.

Although the original cases of multiple and popliteal
pterygium syndromes were clearly defined, there is more phenotypic
variation in both than was originally thought. For example, mild webs
in joints of the upper extremity may be found in patients with
popliteal pterygium syndrome. Adaptive changes in the joints occur over
time. On

radiographic examination, the patella look elongated, and the femoral condyles flattened, because of knee-flexion deformity.

From a management perspective, the determining factors
are the magnitude of scoliosis and the size of the web crossing the
knee. The thoracic vertebral dysplasia, thoracic lordosis, and the
small chest impair lung development, resulting in death in the first
years of life in those with multiple pterygium syndrome. For the
longer-term survivors, management of the spine deformity is identical
to those with nonsyndromic congenital scoliosis. Preoperative MRI
evaluation of intraspinal contents and ultrasound of the kidney are
indicated.

The knee is the joint that limits mobility in both syndromes and is the joint that most determines future ambulatory potential (562,566,567,568).
Traditionally, treatment of the knee begins with physical therapy, but
the effectiveness of this therapy is doubtful. Early popliteal web
surgery is recommended before the onset of adaptive changes in the
articular surfaces, and before further vascular shortening. The nerve
is usually located just under the skin and web, and care must be taken
to avoid nerve damage. The web is resected, and Z-plasty of the skin is
performed. There is a high recurrence rate despite use of braces.
Femoral shortening with an extension osteotomy is often required. If
almost-full knee extension cannot be achieved at surgery, femoral
shortening should be considered, even if during infancy or childhood (569). Gradual distraction techniques can be used, but an advantage over traditional techniques has not been demonstrated (570).
Posterior soft tissue procedures can be combined with distraction
techniques to gradually extend the knee. Femoral shortening techniques
are associated with low recurrence rates of the deformity, and have the
advantage of reducing tension on the neurovascular structures. These
techniques are therefore our treatment of choice.