Indian Journal of Paediatric Dermatology

: 2013  |  Volume : 14  |  Issue : 3  |  Page : 92--94

Klippel-Trenaunay syndrome and type 1 neurofibromatosis: A chance association?

Vikram Singhal, Nutan Kamath, Suchetha Rao 
 Department of Pediatrics, Kasturba Medical College, Manipal University, Manipal, Karnataka, India

Correspondence Address:
Nutan Kamath
Department of Pediatrics, KMC Hospital, Attavar, Mangalore - 575 001, Karnataka


Klippel-Trenaunay syndrome and neurofibroma type I (NF1) are rare disorders with cutaneous and neurological features and not reported to be associated together. We report an 11-year-old female child who presented with extensive skin lesions, giant hemangioma and left lower limb hypertrophy. Her father had features of NF1. We report this case because of its rarity and need for long-term follow-up.

How to cite this article:
Singhal V, Kamath N, Rao S. Klippel-Trenaunay syndrome and type 1 neurofibromatosis: A chance association?.Indian J Paediatr Dermatol 2013;14:92-94

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Singhal V, Kamath N, Rao S. Klippel-Trenaunay syndrome and type 1 neurofibromatosis: A chance association?. Indian J Paediatr Dermatol [serial online] 2013 [cited 2020 Apr 10 ];14:92-94
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Klippel-Trenaunay syndrome (KTS) is a rare congenital vascular bone syndrome characterized by the triad of vascular malformation, venous varicosity and hyperplasia of soft-tissue and bone. [1] Neurofibromatosis type I (NF1) is a common autosomal dominant multi-system, neurocutaneous disorder that predisposes to the development of benign and malignant tumors. [2]

 Case Report

An 11-year-old female child born to non-consanguineous parents presented with painful bluish black skin lesions over the left leg, with difficulty in weight bearing since last 4 years. Dermatological examination revealed multiple cafe-au-lait spots and multiple tender bluish black lesions over the posterolateral aspects of the left thigh and leg [Figure 1] and [Figure 2]. On skeletal examination, the girth and length of left lower limb was more than the right. Systemic examination was normal. Opthalmological examination was suggestive of lisch nodules. Doppler was suggestive of vascular malformation - hemangioma of the subcutaneous and deep fascial planes of the posterior thigh and leg. Father has multiple NFs with café-au-lait spots. A diagnosis of NF1 and KTS was considered based on the presence of clinical and investigations. As the child did not have any complications, parents were reassured and were advised regular follow-up.{Figure 1}{Figure 2}


KTS prevalence is unknown, but around 1000 cases have been reported in the literature so far. [3] KTS was first described in 1900 by Klippel and Trenaunay. [1] The term KTS is often confused with Parker Weber syndrome in which significant arteriovenous fistulas are a feature. The etiology of KTS is unknown with a sporadic occurrence, although a paradominant inheritance pattern has been suggested. [4] It affects males more often than females. Varicosities are predominantly seen in the lower limb and affect the superficial, deep and perforating venous systems. Hemangiomas may also be present. The macular telangiectatic vascular nevi are invariably present at birth. Pain is a very common symptom. Episodes of thrombophlebitis and hemorrhage may occur. Hypertrophy of the affected part may occur at birth or within the first few months or years of life with leg being the most common site, followed by the arms, the trunk and rarely the head and neck. Limb hypertrophy causes increased length (bony involvement) and/or increased girth (soft-tissue involvement). The other occasional abnormalities such as polydactyly, syndactyly, oligodactyly, blue naevi, pulmonary vein varicosities, cerebral aneurysm have been reported. [3],[5]

A thorough history and physical examination are sufficient to diagnose KTS in most cases. In case of major limb length discrepancies, radiological investigations are necessary for early intervention. Evaluation of the deep venous system is done with duplex scanning contrast venography, ultrasonography, contrast venography and arteriography and nuclear magnetic resonance imaging studies. The treatment for KTS is conservative and symptomatic. Chronic venous insufficiency, lymphedema and recurrent bleeding from malformations of the extremity can be managed by compression garments. Cellulitis and thrombophlebitis are managed with analgesics, elevation, antibiotics and corticosteroids. Heel inserts are generally sufficient for limb discrepancies of 1.5 cm or less, whereas for greater discrepancies, orthopedic surgery may be considered. Radiation and endovenous laser therapy also play a role in the treatment. During pregnancy in women with KTS serial ultrasounds should be done because previously asymptomatic arteriovenous malformations within the uterine wall may become pronounced with the additional blood flow to the uterus during pregnancy. [3],[5],[6]

NF1 is also known as von Recklinghausen's disease; peripheral NF. von Recklinghausen's NF which was first described in 1882 by Friedrich Daniel von Recklinghausen. NF1 is caused by mutations in the NF1 gene located on chromosome 17q11.2. [2],[7] Approximately half of cases are due to de novo mutations. [8] The prevalence is estimated at one in 3000 with male and female equally affected. All neural crest cells are affected resulting in excessively proliferation of cellular elements from these cell types throughout the body, forming tumors; melanocytes also function abnormally in this disease, resulting in disordered skin pigmentation and "cafe-au-lait" spots.

Two of the following criteria are required to diagnose NF1: Six or more café au lait patches, NFs, skin-fold freckling, two or more iris lisch nodules, an optic pathway glioma, a specific bony dysplasia, an affected first-degree relative. [2]

Cafe-au-lait is present in 95% of the cases and appears by the age of three. Freckling develops in the majority of children in intertriginous areas. Itching and stinging can result from cutaneous NFs, whereas pain and neurological deficit from pressure on peripheral nerves are features of subcutaneous lesions. Clinically visible plexiform NFs are present in 30% of NF1 cases, of which 7-12% can develop malignant peripheral nerve sheath tumor. Clinical features such as persistent pain change in texture, rapid increase in size and neurological deficit associated with a NF should raise the suspicion of malignancy. Gliomas can occur in the central nervous system, chiefly in the optic pathways, brainstem and cerebellum. NF vasculopathy can result in a cerebral artery stenosis or occlusion, aneurysm and rupture. Scoliosis affects 10% of NF1 patients. [2],[9]

As by the age of 5 years the majority of individuals have enough signs the clinical diagnosis can be made and genetic testing is not needed to diagnose NF1. The identification of pathogenic mutations in over 95% of NF1 patients is possible by current mutation testing. Prenatal testing is possible with foetal DNA extracted from chorionic villus sampling or from aminiocentesis. [2],[7],[9]

As there is no cure for the condition itself, the aim of therapy is to manage symptoms or complications. The surgical removal is the mainstay of treatment for cutaneous NFs and for small superficial lesions occasionally hypertrophic scarring and carbon dioxide laser may be indicated. Chemotherapy may be successful in patients who develop cancerous growth. Special interventions should be performed for early recognition of cognitive impairment so that structured remedial teaching can be offered at an early stage. These patients require regular follow-up and monitoring for possible complications. [2],[9],[10]


There is no relationship between KTS and NF1. This association of KTS with NF1 is not reported to the best of our literature search. There is a need for regular follow-up of these female adolescents transiting into adults.


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