A Rare Triad of Klippel-Trenaunay-Weber Syndrome:Extradural
Arachnoid Cyst, Nevus Flammeus, and Hemihypertrophy
Klippel-Trénaunay-Weber 症候群與蛛網膜囊腫
中文關鍵字:
Klippel-Trénaunay-Weber 症候群，蛛網膜囊腫，葡萄酒色斑，半邊肢體肥大
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Abstract
Objectives: KTW syndrome is a rare congenital disorder with port-wine stain,
hemangioma, venous and lymphatic malformation, and hemihypertrophy. Patients
with abnormal neuroradiographic findings might present with neurological deficits.
However, some cases may not be diagnosed until adulthood because of the obscure
symptoms. More famililarity with Klippel-Trénaunay-Weber (KTW) syndrome is
needed.
Case report: Herein we report a case of KTW involving an 11-month-old boy with
hemihypertrophy and port-wine stains. Based on
recommendation by studies of
neurocutaneous syndromes, we performed a brain magnetic resonance imaging (MRI)
examination for the boy. A large arachnoid cyst in the posterior fossa was found
incidentally, though no neurologic deficits were found at that time.
Conclusions: We recommend brain image studies when encountering a child with
hemihypertrophy and port-wine stain. Long-term follow-up for the neurodevelopment
is warranted in these children.
Key words: Klippel-Trénaunay-Weber syndrome; arachnoid cyst; port-wine stain;
hemihypertrophy
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Introduction
Klippel-Trénaunay-Weber (KTW) syndrome, a neurocutaneous syndrome, is a
rare congenital disorder characterized by vascular lesions of venous and lymphatic
malformation involving the extremities. Its three main features are nevus flammeus
(port-wine stain), venous and lymphatic malformations, and soft-tissue hypertrophy of
the affected limb. [1] Vascular abnormalities in KTW syndrome may affect the capillary,
venous, arterial, and lymphatic systems. Limb enlargement resulting in asymmetry of
the limbs is often seen. This usually involves the lower limbs, but occasionally the
upper limbs as well. Varicose veins and vein enlargement are also a part of KTW
syndrome. Other occasional abnormalities in KTW syndrome include glaucoma,
mental delays, seizures and blood platelet problems. [1]
KTW syndrome has been reported in combination with cerebral and cerebellar
hemihypertrophy, hydrocephalus and micropolygyria. [2–4] Patients with abnormal
neuroradiographic findings may present with neurological deficits, such as
developmental delay, mental retardation and intractable seizures. Herein, we report an
extremely rare case of KTW syndrome in a young boy who had a large arachnoid cyst
in his posterior fossa.
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Case report
The 11-month-old boy had had left-hand hypertrophy with hyperpigmentation
from the time he was born. Hypertrophy with port-wine stains on the left lower
extremity was also noted. The port-wine stains were non-blanchable and reddish to
purplish discoloration patches over his chest, left upper, and lower extremities (Figure
1 and 2). There was no tenderness or itch over the port-wine stains. Therefore, he was
referred to the plastic surgeon for further management. Neurocutaneous syndrome
was impressed initially. Based on clinical features of his limbs hypertrophy and
port-wine stains, the boy was diagnosed as having KTW syndrome.
Blood tests revealed normal hemogram without anemia or thrombocytopenia.
Biochemistry and electrolytes were also within normal limit. To rule out other
congenital anomalies, an abdominal echo and a brain echo were performed. The
abdominal echo showed no visceral hemangiomatous mass and no other anomalies.
While the brain echo revealed no hydrocephalus,
an enlarged posterior horn of the
lateral ventricle was suspected. Brain magnetic resonance imaging (MRI)
demonstrated a posterior fossa cyst, more on the left, a finding compatible with an
arachnoid cyst. The cist was around 4.9 x 2.1 cm (Figure 3 and 4). There was no
abnormal signal intensity in the brain parenchyma. The neurological examination
showed symmetric muscle power and normoreflexia. A careful eye examination by
ophthalmologist was performed and no glaucoma was identified. There was no
macrocephaly, developmental delay, mental retardation, seizures, or other
neurological defects noted at that time. His gait was also normal without limping.
Therefore, the plastic surgeon suggested conservative treatment with a compression
garment and stockings. The parents were taught to perform massage of the affected
limb every day to reduce swelling. The patient was regularly followed-up by the child
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development team in the hospital.
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Discussion
KTW syndrome is a congenital vascular anomaly characterized by a triad of
signs, including varicose veins, cutaneous capillary malformation and hypertrophy of
the bone and/or soft tissue. [5] It is sporadic and may be associated with a translocation
at t(8;14)(q22.3;q13).[6] Mutations in the gene for an angiogenic factor (VG5Q) that
result in increased transcription or activity have been identified in some patients with
this disorder.[7]
KTW syndrome is one of the neurocutaneous syndromes, which include
neurofibromatosis, tuberous sclerosis, Sturge-Weber syndrome, Parkes-Weber
syndrome, ataxia-telangiectasia, and von Hippel-Lindau disease, etc. As a pediatrician,
it is important to differentiate among these syndromes. The characteristic skin lesions
are the key features important to making differential diagnosis among the
neurocutaneous syndromes. Neurofibromatosis type 1 is presented with Café-au-lait
spot, which is a flat, oval eruption of the color of coffee with cream or darker brown.
Sturge-Weber syndrome is characterized by hemifacial port-wine stain over the first or
second division of the trigeminal nerve of the face. The main cutaneous features of
tuberous sclerosis are white leaf-shaped macules in infancy and multiple papules
(angiofibroma) that occur around the nose after early childhood. Shagreen patch and
Koenen’s tumor are also important findings. Other neurocutaneous syndromes also have
specific skin presentations.
KTW syndrome is more common in Asian populations while Sturge-Weber is
more common in western populations. [7] Sturge-Weber syndrome usually presents
with dark skin patches on the face, seizures, and mental delays.
Significant limb
enlargement is not usually a part of Sturge-Weber syndrome. [8] Parkes-Weber
syndrome, which does not usually involve the lymphatic system, may involve the
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heart, which is not typically seen in KTW syndrome. [8]
After reviewing the literature, we found involvement of the central nervous system
in KTW syndrome is rare . [2] It has been reported occur in combination with
hydrocephalus, micropolygyria, cerebral and cerebellar hemihypertrophy.[2–4] One
study reported prevalence of cerebral hemihypertrophy in a series of patients with
KTW syndrome to be 18%.[2] However, there has been no previous reported of
arachnoid cyst associated with KTW syndrome.
Some KTW syndrome may not be diagnosed until adulthood because of the
obscure symptoms with only a birthmark (port-wine stains) over skin. However,
complications of KTW syndrome may develop in adulthood, even in aged individuals.
The diagnostic pitfalls in these patients over this long time period constitute a barrier of
management. Most complications arise from vascular malformation, such as
arteriovenous malformation and arteriovenous fistula, which may cause formation of
blood clots, bleeding, high-output heart failure and pulmonary embolism. Early
diagnosis and preventing the potential complications are important.
Literature reviews also indicate that arachnoid cysts are often asymptomatic and
can remain undetected for years. [9] Therefore, the large arachnoid cyst in posterior
fossa of our case was found very early. Open anterior fontanel for relieving
intracranial pressure may account for negative neurological impairment in our case. [9]
Though his neurological examination and developmental milestones were within
normal range at the time of diagnosis, long term follow-up is sill necessary. In some
cases, neurological symptoms might become increasingly obvious as the children
grow up. If the arachnoid cyst becomes larger, it may press on the central nervous
system and cause headaches, seizures and neurological damage. In severe cases, the
cyst may require surgical draining. Otherwise, follow-up brain imaging once a year is
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suggested.
The involvement of other organs such as the gastrointestinal (GI) tract, liver, spleen,
kidneys, bladder, lungs and heart has been reported. [10] The disease may cause GI
tract bleeding due to vascular malformation of the esophagus, jejunum, colon and
rectum. [4] Therefore, abdominal computed tomography is suggested if there are
symptoms of GI bleeding or visceral hemangiomatous mass effect. [11] Surgery to stop
the bleeding or to remove abnormal blood vessels may be necessary if GI bleeding is
noted. [10]
With regard to the management of the limb enlargement in our case, custom-made
compression stockings were prescribed to reduce swelling, reduce the possibility of
minor trauma, and help blood return from the enlarged body part. Air-driven pumps
can also help to reduce swelling.[10] Some people diminish the redness of their skin
rash by laser treatments using pulses of light even though this required a series of
treatments.[1] We recommend performing an image study, especially MRI, when
encountering a case with hemihypertrophy and port-wine stains. This would help to
find potential neurological abnormalities and provide information about the tissues
affected by abnormal blood flow. Long-term follow-ups for neurodevelopment are
warranted in such cases. Early intervention programs and special education by a child
development team are helpful.
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References
1. Deepti Babu. Thomson Gale (2005): Klippel-Trenaunay-Weber Syndrome.
Retrieved November 20, 2012, from
http://www.healthline.com/galecontent/klippel-trenaunay-weber-syndrome.
2.Torregrosa A, Marti-Bonmati L, Higueras V, Poyatos C, Sanchis A:
Klippel-Trenaunay syndrome: frequency of cerebral and cerebellar hemihypertrophy
on MRI. Neuroradiology 2000; 42: 420-3
3. Gupte GL, Deshmukh CT, Bharucha BA, Irani SF: Klippel-Trenaunay-Weber
syndrome with hydrocephalus: an unusual association. Pediatr Neurosurg 1995; 22:
328-9
4.Shime H, Araki R, Koide H, Miyaji T, Shioda K: A case of
Klippel-Trenaunay-Weber syndrome accompanied by congenital hydrocephalus and
micropolygyria. No To Hattatsu 1992; 24: 353-7
5.Wang ZK, Wang FY, Zhu RM, Liu J: Klippel-Trenaunay syndrome with
gastrointestinal bleeding, splenic hemangiomas and left inferior vena cava World J
Gastroenterol 2010; 16: 1548-52.
6. Wang Q, Timur AA, Szafranski P, et al: "Identification and molecular
characterization of de novo translocation t(8;14)(q22.3;q13) associated with a
vascular and tissue overgrowth syndrome" Cytogenet Cell Genet 2001; 95: 183–8.
7. Tian XL, Kadaba R, You SA, et al: Identification of an angiogenic factor that when
mutated causes susceptibility to Klippel-Trenaunay syndrome. Nature 2004; 427:640.
8. Schook CC, Mulliken JB, Fishman SJ, Alomari AI, Grant FD, Greene AK:
Differential diagnosis of lower extremity enlargement in pediatric patients referred
with a diagnosis of lymphedema. Plast Reconstr Surg 2011; 127: 1571-81.
9. Struck AF, Murphy MJ, Iskandar BJ: Spontaneous development of a de novo
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suprasellar arachnoid cyst. Case report. J Neurosurg 2006; 104: 426-8.
10. Jacob AG, Driscoll DJ, Shaughnessy WJ, Stanson AW, Clay RP, Gloviczki P:
Klippel-Trénaunay syndrome: spectrum and management. Mayo Clin Proc
1998; 73: 28–36
11. Yeoman LJ, Shaw D: Computerized tomography appearances of pelvic
haemangioma involving the large bowel in childhood. Pediatr Radiol
1989;19:414–6.
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Legends to Figures
Figure 1: Hemihypertrophy and port-wine stains over left arm and hand.
Figure 2: Hemihypertrophy and port-wine stains over left leg.
Figure 3: Brain MRI (T1 weighted) showed a large extra-dural arachnoid cyst over
posterior fossa.
Figure 4: Brain MRI (T2 weighted) showed posterior fossa arachnoid cyst, which was
measured 4.9 x 2.1 cm.
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