Article Type : Case Report
Authors : Weber AP, Weber SA, Rueda ACR and Marin DMJ
Keywords : Klippel-Trenauney-Weber; Paediatric; Vascular malformation; Angiodysplasia; Limb overgrowth; Clubfoot
A congenital deformity that causes limb overgrowth in childhood
has multiple genetic and environmental etiologies. One of them is the
Klippel-Trenauney-Weber syndrome (SKT), a rare condition characterized by blood
vessel, soft tissue and bones abnormalities, which may affect structures like
fingers toes or the hole limb, and may worsen preexisting deformities such as
clubfoot. We present the case of a 9-year-old patient with SKT and congenital
clubfoot.
SKT
is a rare congenital disease characterized by the triad of varicose veins, capillary
malformations and hypertrophy of soft tissue and bone. This can cause limb
overgrowth and deformities mainly in fingers and toes and may present
life-threatening vascular complications. Its etiology is unknown. The treatment
is multidisciplinary, intended to improve quality of life, surgical correction
of deformities, attend complications and avoid sequels. We present the case of
a 9-year-old patient with SKT and congenital clubfoot.
A 9-year-old female patient with no relevant family history.
Since the age of 6 she presented asymmetry of the lower extremities and
clubfoot, edema of the left pelvic limb and claudication. In 2011, surgery was
performed to correct the clubfoot, however, it persisted along with the
asymmetry and the claudication, getting worse with time. On physical
examination, the left pelvic limb was 4 cm larger compared to the right. An
increase in volume was also noted mainly in the leg and ankle, due to the
muscles, lymphatic vessels and varicose veins abnormalities. Port-wine stains
were observed on thorax, left leg and abdomen. In addition, a “cafe-au-lait”
skin stain was seen on the same leg (Figure 1). Angio-CT scan of pelvic limbs
reported multiple varicose venous malformations and arterio-venous fistulas in
the left pelvic limb, with early venous filling, and soft tissue and bone
hypertrophy, suggestive of SKT (Figure 2). Genetic studies reported 46 XX
genotype without numeric or structural chromosomal abnormalities. Biopsy of the
“cafe-au-lait” skin stain was taken from the left leg to rule out
neurofibromatosis discarding this diagnosis because none were found. Other
diagnostic possibilities associated with limb overgrowth such as
Beckwith-Wiedemann, Soto or Proteus syndrome were also excluded. With all the
previous data, the diagnosis of SKT was confirmed.
To correct the asymmetry of the pelvic limbs, an epiphysiodesis of the left distal femur was performed. An anterior and posterior Blump’s staples were placed between the diaphysis and the metaphysis temporarily to improve symmetry by slowing bone growth (Figure 3). Six months later, to correct completely the asymmetry, proximal distal and tibial femoral epiphysiodesis and clubfoot plasty were performed. The patient evolved adequately; the clubfoot was completely corrected. With physiotherapy she improved her walking. During follow-up, the patient's growth was assessed and the asymmetry was corrected. To preserve symmetry, further epiphysiodesis of the right limb was proposed if needed. Currently, the patient is walking normally, without pain and performing her daily activities without difficulties. She attends medical consultation for follow-up and periodic examinations to detect other possible complications of SKT.
Figure 1: Discrepancy of 4cm in length between lower extremities, with increased muscle mass and port-wine stain in the left limb, and a “cafe-au-lait” skin stain in the same leg.
Figure 2: Angio-CT scan with soft tissue hypertrophy and multiple venous malformations.
Figure 3: Epiphysiodesis with
Blump’s staple placement.
SKT is a rare congenital disease of unknown cause,
characterized by a triad that consists of vascular malformations mainly of the
deep venous system and capillaries, skin color changes (port-wine stain) in up
to 80-98% and varicosities in 70-80% of cases [1]. These are the most frequent
clinical manifestations and the causes of most of the life-threatening
complications. These anomalies affect the extremities causing hypertrophy of
muscle, lymphatic, fat and bone tissue. They usually occur in only one limb,
although in rare cases it can affect two at the same time. The main symptoms
are pain and walking abnormalities. Overgrowth of the limb, hypertrophy and
muscular and tendon flaccidity can cause or worsen other associated deformities
such as clubfoot like the case of the patient reported here, and should be
taken into account for the complete management of this problem [2,3].
The frequency of this pathology is unknown; however,
it has been reported in 1: 100,000 live births [4]. In patients with a
first-degree family history it increases up to 1: 880 [5]. Although it can
affect both men and women, “it seems to have certain predilection for men” goes
Ceballos et al. [6] mentioned that many cases of SKT are de novo since there
are no first-degree relatives with a diagnosis of this disease. However, in
those in which the disease has been traced in the family tree, the presence of
an autosomal dominant pattern has been demonstrated. This suggests that it may
be caused by a genetic defect in homozygous patients. The association with
angiogenic factors such as the AGGF1 and PIK3CA genes related with vascular and
lymphatic overgrowth seems to be of relevance [7]. This disease can be
associated with other genetic syndromes that affect the skin and vascular
system such as neurofibromatosis [8]. In this patient who had suggestive
lesions that looked like “cafe-au-lait”, neurofibromatosis was ruled out.
The etiology is still unknown. There are theories
that point to an alteration during fetal growth, in the process of development
of vascular structures. These alterations usually manifest themselves in
childhood or adolescence. They may be limited to the skin, subcutaneous tissue
or muscles, however, in some cases they affect all these areas causing
progressive deformities especially in lower extremities. The most frequent and
serious complications are disseminated intravascular coagulation (DIC) 88% and
pulmonary thrombosis in 10%, which are linked to the vascular malformations.
Bleeding from the digestive tract has also been reported [9,10]. The disorders
that are associated with the limb overgrowth in pediatric patients have a
multifactorial etiology. There are endocrine, nutritional and environmental
factors, with different genetic causes such as those identified in other
pathologies classified overgrowth syndromes in those with vascular involvement
such as SKT, and those with only somatic components [11]. The overgrowth of
soft and bone tissue caused by abnormal vascular proliferation causes the
increase in volume, diameter and length of the limb. Among all the
malformations mentioned in the literature caused by this disease, limb
deformities have been reported between 50 and 94%, with the lower extremities
being the most affected in up to 95% of cases unilaterally. Vascular
malformations with venous and lymphatic hypertension that cause alterations of
the extremities may be present since intrauterine life.
McGrory et al. reported
in a series of 108 patients the deformities in the SKT. Most of them were found
in fingers and toes such as macrodactyly, syndactyly, polydactyly or
clinodactyly. Other deformities reported were, five patients with idiopathic
scoliosis, one with clubfoot and other with flat foot and patellar subluxation,
one patient with congenital hip dislocation, another with knee hemartrosis,
another with carpal tunnel syndrome and one with Ehlers-Danlos syndrome [12].
Due to the type of associated pathologies in SKT that have been found in some
case reports and series such as the one mentioned above, a hypothesis that a
collagenopathy could be associated with SKT can be made since most of these
pathologies may have a defect of this protein, possibility that has been not
studied yet as far as we know. Collagen abnormalities as proposed in one of the
new theories of the pathogenesis of the clubfoot, such as "fibrous
retraction," may be involved [13]. The diagnosis of this disease is
possible in the presence of the mentioned clinical signs. Especially when the vascular
malformations, the port-wine skin stain, the presence of varicose veins, the
overgrowth of a limb, or the complete triad that characterizes this disease is
present, supported by imaging studies. The most helpful studies for diagnosis
are the Doppler ultrasound to evaluate vascularity abnormalities, complemented
with contrasted computed angio-tomography to assess the extent of the problem
and magnetic resonance with gadolinium to distinguish lymphatic malformations.
The limbs length asymmetry can be evaluated with plain X-rays [14]. There is no
definitive cure for SKT. The management of this problem must be
multidisciplinary, aiming primarily to improve the quality of life and
functionality, and to prevent or treat the complications such as coagulopathies.
As a treatment for capillary lesions, laser therapy is recommended, especially
if the lesions are on face and trunk. For the treatment of varicose veins and
lymphedema in the extremities, compression stockings or sclerotherapy are
useful. Anti-angiogenic medications are promising for the treatment of vascular
malformations and the reduction of complications [1]. Surgery is indicated in
patients with symptoms or complications associated with this problem that
cannot be solved with conventional treatment. If complications such as
exaggerated limb growth in both length and volume, coagulopathies, incoercible
bleeding or deformities that cannot be corrected with medical or surgical
treatment, limb amputation may be indicated. To treat the overgrowth and asymmetry
of the limbs, corrective surgery is necessary. Epiphysiodesis is one of the
most used procedures when the asymmetry is greater than 2 cm as in the case of
this patient [15].
SKT is a rare disease, difficult to diagnose, which
should be suspected in the pediatric patient presenting vascular abnormalities
and limb deformities, to implement appropriate early prevention measures and
avoid complications. In some cases, such as the one reported here, they can be
associated with other malformations such as clubfoot that can be treated with
opportune surgery.