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Pediatrics and Neonatology (2017) xx, 1e4

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Short Communication

Medical treatment of a female patient with

complicated KlippeleTrenaunay syndrome
Fang-Liang Huang a,b, Han-Yu Chen b, Te-Kau Chang a,c,*

Department of Pediatrics, Taichung Veterans General Hospital, Taichung, Taiwan
Hungkuang University, Taichung, Taiwan
Department of Pediatric, Cheng Hsin General Hospital, Taipei, Taiwan

Received Feb 15, 2017; received in revised form Apr 27, 2017; accepted Nov 15, 2017
Available online - - -

1. Introduction forearm was brought to our hospital through an arrange-

ment with the Formosa Budding Hope Association. Her birth
KlippeleTrenaunay syndrome (KTS) is a rare and sporadic history indicated a full-term, normal, and spontaneous
congenital vascular disorder characterized by capillary delivery using a vacuum extractor and a birth body weight
and/or venous malformations or extensive distribution, of 3300 g. According to her mother, she had had an
along with an early onset of varicose veins, in addition to extremely large right upper limb that did not obviously
hypertrophy of the affected tissues.1 KTS has also been change in size since birth. Since approximately 1 year old,
postulated to be a result of an embryonic developmental she had been suffering from frequent nose and mouth
disorder of mesodermal tissues that affects angiogenesis at bleeding, in addition to ecchymosis over her limbs and
different stages, possibly following an intrauterine insult.2,3 trunk area. Occasionally, a cutaneous bleeding ulceration
The conventional treatments for KTS are conservative spontaneously developed over her right hand; additionally,
compression, sclerotherapy, lasers, and surgery4,5; howev- oozing from ulcerations was noted.
er, there has been little discussion in the literature A physical examination upon admission revealed normal
regarding treatment involving internal medicine. findings, with the exception of weakness and hypertrophy in
Herein, we report the case of a young girl with the right upper extremity, along with bleeding wounds on her
congenital KTS who was treated with both internal medi- right hand. Her upper left extremity was normal in size with
cine and compression therapy, which had successfully good mobility. Anthropometric measurements confirmed
preserved the function of her right upper extremity during that the right upper limb was larger than the left [length
her most recent follow-up visit, which was 6 years after right:left (R:L), 25.5:22.5 cm; midupper arm circumference
completion of treatment. R:L, 30.5:12.5 cm; and midforearm circumference R:L,
26.5:12.5 cm]. Extensive port-wine staining over the right
limb was noted (Fig. 1A). Developmental growth delay was
2. Case report also noted, as she was unable to stand or walk until the age of
2 years. Her intelligence was normal for her age.
A 2-year-old girl from Cambodia with congenital gigantism A complete blood count revealed a hemoglobin level of
of the right upper extremity from the shoulder to the 10.8 g/dL, white blood cell count of 12.6  109 cell/L, and
platelet count of 9  109/L. Serum biochemistry and
* Corresponding author. Department of Pediatrics, Taichung coagulation investigations, including bleeding time, pro-
Veterans General Hospital, No. 1650, Taiwan Boulevard Sect. 4, thrombin time, activated partial thromboplastin time, and
Taichung City 40705, Taiwan. Fax: þ886 4 2374 1359. fibrinogen, were all within normal ranges. An X-ray of her
E-mail address: (T.-K. Chang).
1875-9572/Copyright ª 2017, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-
NC-ND license (

Please cite this article in press as: Huang F-L, et al., Medical treatment of a female patient with complicated KlippeleTrenaunay
syndrome, Pediatrics and Neonatology (2017),
2 F.-L. Huang et al

Figure 1 (A) A 2-year-old girl presented with congenital gigantism of the right upper extremity from the shoulder to forearm with
extensive port-wine staining over the right limb (B) Multidetector-row Computed Tomography (MDCT) shows a diffuse circumfer-
ential soft-tissue hypertrophy with capillary malformation, muscle fatty infiltration, venous aneurysms and malformations (C) The
right arm without recurrent progressive enlargement was observed when the girl was 4 years old.

right arm revealed multiple foci of a well-defined osteol- chromosome study was performed on the G-banded chro-
ysis, surrounded by a sclerotic margin at the right humerus, mosomes from peripheral blood cultures, which revealed
and a proximal ulna where the most prominent area was 46, XX without any abnormality. A genetic test showed no
located at the distal third of the humerus (Supplementary E133K change in the VG5Q gene.
Fig. 2A). The patient received platelet transfusion to stabilize
Magnetic resonance angiography (MRA) and both her bleeding tendency and thrombocytopenia. After
multidetector-row computed tomography (MDCT) showed consultations with orthopedic, plastic, and vascular sur-
diffuse circumferential soft-tissue hypertrophy with capil- geons from our hospital, it was decided that surgical man-
lary malformation, fatty muscle infiltration, venous aneu- agement, such as a right arm amputation or a debulking
rysms, and malformations over both superficial and deep procedure, was not a therapeutic option that would both
veins; bone expansion and erosion over the right humerus, preserve arm function and avoid the high risk associated
along with the proximal ulna over the right upper limb, was with anesthesia6 and high bleeding tendencies in patients
also discovered (Fig. 1C). No evidence of arteriovenous with KTS. Therefore, the patient received internal medical
malformation (AVM) or deep vein thrombosis was observed. treatment and compression therapy and participated in a
Lymphoscintigraphy showed a malfunction of the lymphatic rehabilitation program at our ward. After a full cardiovas-
system in the right upper extremity. An arteriogram showed cular and respiratory review and discussion with her family,
a markedly increased number of abnormal capillary com- the initial regimen prescribed was oral propranolol (2 mg/
ponents and small varicose veins over the medial side of kg/d) for 6 months and prednisolone (an initial dosage of
right upper limb. The patient’s venogram revealed 3 mg/kg/d for the first month, followed by 2 mg/kg/d) for a
abnormal varicose veins running around the right cephalic total of 3 months. Intravenous vincristine (0.05 mg/kg/wk
vein in the lateral part of the upper arm. for 4 wk) was also given during the first month. A rehabil-
The capillary, venous, and lymphatic malformations with itation program of regularly scheduled sessions was estab-
varicose veins and hypertrophy of the affected tissues lished to improve function in her right arm. In addition, the
affecting her right arm were identified. A clinical diagnosis patient wore a custom-made elastic sleeve to compress her
of KTS was then established based on these findings. A large right upper extremity.

Please cite this article in press as: Huang F-L, et al., Medical treatment of a female patient with complicated KlippeleTrenaunay
syndrome, Pediatrics and Neonatology (2017),
Medical treatment a child with KTS 3

As a result of this treatment, the circumference of the rejected this approach to preserve her right arm and avoid
right midupper arm reduced from 30.5 cm to 23 cm (a any potential surgical risks, particularly as she had bleeding
reduction of 24.6%) and that of the midforearm reduced tendencies.
from 26.5 cm to 21.5 cm (a reduction of 18.9%) during the 6- Although compression therapy helps to diminish the
month treatment period. The patient was able to stand, symptoms of venous insufficiency and lymphedema, it has
walk, and raise her right hand over her head upon no effect on the ultimate size of the limb.5 Considering our
completion of treatment. There were no obvious compli- patient’s young age, we decided that using radiofrequency
cations from the medical treatment, nor any further ablation and sclerotherapy to treat her vascular malfor-
thrombocytopenia or bleeding during the treatment period. mations was not appropriate. Therefore, we opted to use
At the 2- and 6-year follow-up, the function of the right arm internal medical treatment despite the lack of reference
was favorable and the patient showed no signs of recurrent data available in medical publications about treating KTS in
progressive enlargement of the limb. At the time of writing, children using internal medicine.
the patient is 8 years old and growing at a normal rate for a Regarding the uncertain etiology of KTS, it is generally
girl of her age. The most recent MRA of her right arm considered to involve defects in angiogenesis and regula-
revealed regression in size, and X-ray revealed a dramatic tion of both vessel and tissue growth; therefore, anti-
change in the right humerus, which had a normal appear- angiogenic agents were used to target the angiogenesis and
ance (Supplementary Fig. 2B). malformation of vessels and tissue. Vincristine is capable of
modulating angiogenesis as an antiangiogenic agent due to
its ability to directly attack the host vasculature, which
3. Discussion causes an endothelial retraction, swelling, and disrup-
tion.12 It has also been used to successfully treat capillary-
KTS is a term used to describe the combination of a cuta- lymphatic malformation.12 The mechanisms through which
neous capillary malformation, varicose veins or venous prednisolone controls vascular anomalies remain unclear,
malformation, and soft tissue and/or bony hypertrophy of an although the medication appears to increase vasoconstric-
extremity. The clinical presentation of the current case tion, inhibit fibrinolysis, and disrupt angiogenesis.13
included all the aforementioned conditions. KTS is typically Meta-analyses have indicated that propranolol has a
unilateral, affecting an isolated upper extremity in 5%e11% dramatic impact on the treatment of infantile hemangi-
of cases.5 It is thought to occur sporadically, with an inci- omas without causing any severe side effects.14 The
dence rate of approximately 1 per 100,000 live births, and possible mechanisms of action for propranolol are vaso-
carries no predilection for a particular sex or race.7 Because constriction, inhibition of angiogenesis, and the triggering
no AVM was noted in our case, KTS was easily distinguished of apoptosis in capillary endothelial cells.15 A case series
from ParkereWeber Syndrome, in which an enlarged ex- article reported that propranolol improved symptoms of
tremity occurs due to being related to an underlying AVM. lymphatic anomalies, including cases of patients with
Although the mortality rate amongst KTS patients is low KTS.16 We used the three antiangiogenic agents and ach-
(approximately 1%),5 our patient suffered from lift- ieved an excellent response within a relatively short
threatening complications, namely severe thrombocyto- treatment period. We did not use interferon or cyclophos-
penia with mucosal bleeding and infectious ulcerations on phamide, as they are associated with more side effects.
the right hand. The patient’s suffering from thrombocyto-
penia may have been due to long term active bleeding of
4. Conclusion
the lesion area with platelet consumption, or an association
with Kasabach-Merritt Syndrome-like symptoms in KTS.
After treatment, the patient’s platelet count recovered to To the best of our knowledge, we are the first to report on
a normal level within one month. The syndrome in the the use of combination therapy comprising three anti-
present case is rare, while it exactly matched the clinical angiogenic agents, vincristine, prednisolone and proprano-
diagnostic definition and its associated complications, lol, to successfully treat a child with congenital KTS. In
obviating the need for a pathological biopsy examination.2 summary, congenital KTS may be managed through the use
Although this syndrome was first chronicled more than of internal medicine and conservative therapy, as they are
one-hundred years ago, the etiology of KTS remains un- capable of achieving a dramatic response, which allows for
clear. With respect to the suspicious etiology of KTS, it is the preservation of function in the affected extremity.
generally considered to involve defects in both angiogen- However, it should be noted that experience with KTS in
esis and regulation of vessel and tissue growth.2 The pediatrics remains limited.
increased angiogenesis of KTS may be due to mutations in
the VG5Q gene through transcription and increased activ- Conflict of interest
ity.8 In the present case, genetic study revealed no muta-
tion of the VG5Q gene, and there was no associated mass or None.
tumor formation during 6 year follow-up.
The management of KTS is complex.4 Surgery has been
considered the standard therapy for vascular malforma- Acknowledgement
tions,9 while amputation of the limb or surgical debulking has
been applied to treat progressive soft-tissue enlargement The authors acknowledge the assistance of the Formosa
when it causes interference with activities of daily living.10,11 Budding Hope Association, which made the arrangements to
We also initially considered surgical management but bring the patient to our hospital.

Please cite this article in press as: Huang F-L, et al., Medical treatment of a female patient with complicated KlippeleTrenaunay
syndrome, Pediatrics and Neonatology (2017),
4 F.-L. Huang et al

References 6. Barbara DW, Wilson JL. Anesthesia for surgery related to

Klippel-Trenaunay syndrome: a review of 136 anesthetics.
Anesth Analg 2011;113:98e102.
1. Klippel M, Trenaunay P. Du naevus variquex osteohyper-
7. Sung HM, Chung HY, Lee SJ, Lee JM, Huh S, Lee JW, et al.
trophique. Arch Gen Med 1900;3:641e72.
Clinical experience of the Klippel-Trenaunay syndrome. Arch
2. Oduber CE, van der Horst CM, Hennekam RC. Klippel-Trenaunay
Plast Surg 2015;42:552e8.
syndrome: diagnostic criteria and hypothesis on etiology. Ann
Plast Surg 2008;60:217e23.
3. Baskerville PA, Ackroyd JS, Browse NL. The etiology of the Appendix A. Supplementary data
Klippel-Trenaunay syndrome. Ann Surg 1985;202:624e7.
4. Gloviczki P, Driscoll DJ. Klippel-Trenaunay syndrome: current Supplementary data related to this article can be found at
management. Phlebology 2007;22:291e8.
5. Jacob AG, Driscoll DJ, Shaughnessy WJ, Stanson AW, Clay RP,
Gloviczki P. Klippel-Trénaunay syndrome: spectrum and man-
agement. Mayo Clin Proc 1998;73:28e36.

Please cite this article in press as: Huang F-L, et al., Medical treatment of a female patient with complicated KlippeleTrenaunay
syndrome, Pediatrics and Neonatology (2017),