Print version ISSN 0365-0596
An. Bras. Dermatol. vol.85 no.1 Rio de Janeiro Jan./Feb. 2010
Cristiano do Amaral de LeonI; Luiz Roberto Braun FilhoII; Maigrei Dani FerrariIII; Bruno Luiz GuidolinIV; Bruna Jardim MaffessoniV
IPreceptor of the Inpatient Pediatric Unit of the University Hospital of Universidade Luterana do Brasil (ULBRA) - Canoas (RS), Brazil
IIPreceptor of the Inpatient Pediatric Unit of the University Hospital of Universidade Luterana do Brasil (ULBRA) - Canoas (RS), Brazil
IIIStudent of Medicine, Universidade Luterana do Brasil (ULBRA) - Canoas (RS), Brazil
IVStudent of Medicine, Universidade Luterana do Brasil (ULBRA) - Canoas (RS), Brazil
VStudent of Medicine, Universidade Luterana do Brasil (ULBRA) - Canoas (RS), Brazil
Klippel-Trenaunay syndrome is characterized by a triad of port-wine stain, varicose veins with or without venous malformations, and bony and soft tissue hypertrophy. It usually affects only one extremity. Its cause continues to be investigated, although theories abound. There is no predilection for gender or any particular ethnicity, and it appears more frequently at birth, childhood or adolescence. We report the case of an 8-year-old boy with this syndrome.
Keywords: Hypertrophy; Port-wine stain; Vascular malformations
Klippel-Trenaunay syndrome (KTS) is characterized by a triad of port-wine stain, varicose veins, and bony and soft tissue hypertrophy. It generally affects only one extremity.1 Lesions are present at birth and in approximately 75% of patients they appear before 10 years of age.2 The difference between KTS and Klippel-Trenaunay-Weber syndrome (KTWS) is that the latter includes significant arteriovenous malformations in the affected extremity. 3
The origin of this syndrome continues to be investigated, and many theories are discussed. Some authors believe that these venous abnormalities result from a deep venous obstruction or yet from deep venous atresia, leading to edema and hypertrophy of the extremity.4.5 Although KTS is a sporadic condition, studies report familial cases of KTS that have not been inherited from a Mendelian pattern, thus suggesting a multifactorial inheritance. 6 Later studies conducted by Happle suggest that the inheritance of a single abnormal gene could explain the development of this syndrome, as well as the occurrence of sporadic and familial cases. Lesions follow a mosaic pattern, where heterozygotes of a single defective gene would be phenotipically normal, but the defective allele could be transmitted for many generations. The trait would only be expressed when a somatic mutation occurred in the normal allele, in the early embryogenic phase, originating a population of clonal cells for the mutation of KTS. 7
This syndrome occurs with little frequency in our environment; however, it deserves attention because several studies have reported a pattern of autosomal dominant inheritance in some individuals, and most of these cases are sporadic. Gene theory suggests that a single gene with a lethal defect in homozygous individuals is involved in the case.
M.M.E.L., 8 years old, male, was admitted to the pediatric unit of Hospital Universitario de ULBRA - Canoas-RS, in April 2008, with a bleeding vascular lesion on his left auricular pavilion, congenital cutaneous vascular lesions (cutis marmorata), and polypoid hemangiomas. All anomalies were observed on his left hemibody. The patient had had the lesion on his left auricular pavilion for two weeks, with insidious bleeding interspersed with periods of improvement. The patient had been presenting polypoid hemangiomas on his left hemibody for two years and undergoing lesion resection. The patient had no family history of the disorder and had not received a conclusive diagnosis in any of the hospitals he had been referred to.
In the physical examination upon admission the patient's vital signs were stable. Erythematous lesions of vascular origin in hemiface, cervical region, and upper limb, all on the left side, were observed. Facial asymmetry was also diagnosed (Figure 1). After initial evaluation, the patient was hospitalized with the diagnosis of Klippel-Trenaunay syndrome for general and genetic surgery evaluation.
Surgical evaluation revealed hemangioma or vascular malformation in hemiface and cervical region with previous bleeding, with no signs of infection and/or active bleeding at the moment; vegetating lesion on the left auricular pavilion with light bleeding, which was later cauterized. Genetics evaluation diagnosed facial asymmetry (elongation on left side) and apparent body asymmetry (elongation on left hemibody) (Figure 2). These symptoms were compatible with the diagnosis of KTS.
After diagnosis, an evaluation by the vascular surgery team to investigate the presence of arteriovenous malformations on the left extremity, in order to differentiate KTS from KTWS, was requested. An arterial and venous ecodoppler study of the lower left limb was conducted and no anomalies were found. After the diagnosis of KTWS was dismissed, trauma evaluation to measure discrepancy due to left lower limb megaly was performed. Neurologists also evaluated the patient and diagnosed deviation of labial commissure to the right side, eyeball asymmetry (bigger on the left side), and facial asymmetry (elongation on left side). Hyperactivity and cognitive deficit were not observed.
The patient was discharged from the hospital in good clinical condition and continued to see a dermatologist for laser treatment of port-wine stains. He receives follow-up care from a traumatologist for evaluation of the discrepancy between lower limbs; from the vascular surgery team, for evaluation of varicose veins, which were not yet visible on physical examination, and from the genetics team, for investigation of possible causes.
Klippel-Trenaunay Syndrome was initially described in 1900 as a triad of cutaneous capillary hemangiomas, bony and soft tissue hypertrophy, and venous dilations. The disorder usually affects one body segment and has several clinical manifestations.8
Most patients show the three symptoms of the clinical syndrome, and hemangioma is often the first to appear.3 Port-wine stain or flat hemangioma is a vascular malformation present at birth and that does not show tendency toward involution. It is often unilateral and segmented, never crossing the midline. It increases in proportion to the child's growth and may involve any part of the body, although face and cervical region are the most commonly affected areas. Lesions may be light pink in infancy and become progressively darker (dark red) as the child ages.9 Hemangiomas may be limited or extend to deeper areas of skin, including bones, muscles, and organs, worsening the prognosis of the disease.
Varicose veins observed in patients with the syndrome may be noticed in early infancy, but they generally become prominent in a later stage and progress until adolescence.10 They are a large and lateral vein, which starts on the foot or leg, proximally, and extends until the buttocks or gluteus region. These areas may remain stable or enlarge gradually, causing pain, lymphedema, trombophlebitis, and ulcers.3 Hypertrophy is the third symptom to appear in the syndrome and it can be secondary to length increase (bone involvement) and/or circumference increase (soft tissue involvement). It can be observed at birth and progresses during the first years of life. In adolescence, when the child's growth cycle period has finished, the limb will stop growing.
In the case reported, the patient showed port-wine stains in the face, cervical region, and upper limb, all on his left hemibody. Hemangiomas were present at birth and darkened with time, increasing their surface area. Varicose veins were not visible on physical and imaginologic examination of lower limbs. A slight elongation of the patient's left hemibody, both in length and circumference, without hypertrophy of lower limbs, was visible.
KTS should be suspected in all infants with capillary malformations involving one extremity of the body from birth. Differential diagnosis for KTS is KTWS, Proteus Syndrome, Maffucci Syndrome, among other nonsyndromic capillary malformations of the skin.10
There is no cure for this disorder. Therapeutic objectives seek to improve the patient's condition and treat the consequences of severe lesions and length discrepancy. Treatment of port-wine stains is done with pulsed dye laser therapy. It is best to start treatment early because younger children require fewer sessions and show more favorable results. Treatment yields better results when applied to lesions in the face and trunk, as compared to extremities. Nevertheless, it only contributes to the superficial treatment of hemangiomas.11 When varicose veins are present, compression stockings are recommended for venous insufficiency. Surgical treatment is only recommended in symptomatic cases of superficial varicose veins.12 The use of orthopedic braces is a good option to prevent the development of vertebral deformities in case of hypertrophy of the lower limbs. With time, corrective bone surgery may be necessary to treat significant limb length discrepancy.1
In conclusion, patients diagnosed with KTS must be evaluated once a year or more frequently, based on clinical recommendation, in order to keep the disease under control. If the disorder progresses, imaginologic examination should be done and surgical intervention should be considered for the correction of lower limb length discrepancy. Research in genetics should be encouraged so that in the future we may be able to understand the etiology of this disease.
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Mailing Address: Recebido
em 26.02.2009. *
Work conducted at the Division of Inpatient Pediatrics at Universidade Luterana
do Brasil (ULBRA) - Canoas (RS), Brazil.
Maigrei Dani Ferrari
Rua Oswaldo Cruz, n. 1483 - Santa Catarina
95032 400 Caxias do Sul, RS
Tel./Fax: 51 9661-0602 54 3224-4655
Aprovado pelo Conselho Consultivo e aceito para publicação em 17.06.09.
Conflict of interest: None
Financial support: None
* Work conducted at the Division of Inpatient Pediatrics at Universidade Luterana do Brasil (ULBRA) - Canoas (RS), Brazil.