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Klippel–Trenaunay syndrome with Chiari I malformation: A rare correlation with literature review

 Department of Neurosurgery, All India Institute of Medical Sciences—Bhubaneswar, Bhubaneswar, Odisha, India

Date of Submission07-May-2021
Date of Decision13-Jul-2021
Date of Acceptance18-Jun-2021
Date of Web Publication07-Jan-2022

Correspondence Address:
Arunkumar Sekar,
Department of Neurosurgery, All India Institute of Medical Sciences—Bhubaneswar, 751019, Odisha.
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpn.JPN_107_21



Klippel–Trenaunay syndrome (KTS) is characterized by localized vascular naevus, congenital or early infantile varicosities, and soft tissue or bony hypertrophy. It was been described to be associated with hemimegalencephaly and Chiari I malformation in isolation. Here we present a case of a child who presented with KTS associated with both hemimegalencephaly and Chiari I malformation. The clinical presentation of the child and the likely pathogenesis of association with Chiari I malformation in KTS are discussed. The overall management of KTS with Chiari 1 malformation is reviewed.

Keywords: Chiari I malformation, hemimegaloencephaly, Klippel–Trenaunay syndrome

How to cite this URL:
Datta D, Sekar A, Sahu RN. Klippel–Trenaunay syndrome with Chiari I malformation: A rare correlation with literature review. J Pediatr Neurosci [Epub ahead of print] [cited 2023 Oct 3]. Available from: https://www.pediatricneurosciences.com/preprintarticle.asp?id=335184

   Introduction Top

Klippel–Trenaunay syndrome (KTS) was first reported by Hilaire in 1832 and recognized as a separate disease entity by Klippel and Trenaunay in 1900.[1] It usually occurs as a triad of localized vascular naevus, congenital or early infantile varicosities, and hypertrophy of soft tissue or bone. The neurological manifestations of KTS are varied and affected individuals may present with macrocephaly, microcephaly, and cerebrovascular malformations.[1] Chiari I malformation as an association with KTS has been less reported. Here we discuss about the presentation of a child with KTS and Chiari I malformation and the relevant management aspects.

   Case Report Top

A 10-year-old girl was referred to us for chronic pain in the nape of the neck. Her ordeal started as child when parents noticed swelling in the right side of her face. Over the next few years, there was a noticeable difference in size of her lower limbs which later became a generalized swelling, starting in right and then in the left leg. For the past 1 year, she had complaints of multiple episodes of vaginal bleeding, with an increase in size of her right breast. On examination, she had asymmetrical hypertrophy of her legs along with the presence of multiple dilated tortuous veins. There was port-wine staining in her right axilla along with presence of soft tissue syndactyly of her foot and cubitus varus (right>left). On gynecological examination, she had multiple areas of bleeding spots in the vaginal wall. There was almost 9 cm discrepancy in the limb length and also in girth of the foot [Figure 1]A–C.
Figure 1: (A) Soft tissue hypertrophy of the right side of face. (B) Port-wine staining of right lateral trunk. (C) Bilateral lower limb hypertrophy with soft tissue syndactyly of right 2nd and 3rd toe. (D) T2W axial image showing right hemimegalencephaly and eccentric dilatation of right lateral ventricle. (E) T2W sagittal image showing Chiari I malformation

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A biopsy taken from vulval lesion showed the presence of vascular malformation and muscular hypertrophy, consistent with KTS. She was started on tacrolimus for vaginal vascular lesions. In view of her persistent headache over the past year, she was evaluated with magnetic resonance imaging (MRI) brain and referred to us for further management. She was neurologically stable. She had a mild pelvic tilt toward the left due to the limb length discrepancy. Rest of the spine examination was normal.

MRI of the brain revealed hypertrophy of right cerebral and cerebellar hemispheres with asymmetric dilatation of the right lateral ventricle. A 6 mm caudal displacement of the cerebellar tonsils from the foramen magnum was present. MRI of the rest of the spine did not reveal any evidence of syringomyelia [[Figure 1D] and E]. In view of the mild pelvic tilt and intermittent neck pain and her MRI findings, she was advised to be on close follow-up with imaging to look for development of syringomyelia and progression to scoliosis. She was suggested that foramen magnum decompression may be required if her complaints worsened. She has since been on routine follow-up for the past 1 year and her headache has improved with symptomatic treatment.

   Discussion Top

KTS is a rare anomaly which has an incidence of 1 in 100,000 without any race, sex, or geographical predilection.[2 The etiopathogenesis of KTS is not well defined. PIK3CA gene mutation is found to be associated with KTS. The 110 kDa catalytic α-subunit of PI3K is encoded by the PIK3CA. Gain-of-function mutations in the PIK3CA lead to activation of AKT via the tyrosine kinase-PIP2-PIP3 pathway. This causes mTOR1-mediated cell proliferation and clinically recognizable tissue overgrowth.[2] However, cases of KTS without PIK3CA gene mutation have also been reported in literature, which indicates that multiple genes may be involved in the initiation and progression of the disease. This syndrome is now considered to be a part of the PIK3CA-related overgrowth spectrum (PROS). Other than the PIK3CA gain-of-function mutation, multiple other mechanisms have been proposed to explain the development of KTS, such as anomaly of the spinal cord causing decrease in the autonomic control of the capillaries in the distribution of the spinal nerves (metameric distribution) leading to the vascular skin lesions. Aberrant vasculogenesis and anomalies in the deep venous system can also cause limb hypertrophy due to passive hyperemia. Generalized mesodermal defects cause disturbed angiogenesis with persistence of microscopic arterio-venous communications leading to limb hypertrophy.

The diagnostic criteria proposed by Oduber et al. and the International Society for the Study of Venous Anomalies classification state that a congenital vascular malformation must be present and must include capillary malformations or venous malformations along with disturbed bone or soft tissue growth (either hypertrophy or hypotrophy). Arteriovenous malformations (AVMs) if present must be small and clinically insignificant.[1] Clinically significant AVM points toward a diagnosis of Parkes– Weber syndrome More Details.[1]

Chiari I malformation is characterized by cerebellar tonsillar herniation beyond the foramen magnum and presents with clinical features of brainstem herniation or syringomyelia. In the reported case, there was no syringomyelia and the patient was asymptomatic. The cause of Chiari I malformation in KTS is not clear but in this case, it may be due to the hemimegaloencephaly causing crowding at the posterior fossa with cerebellar tonsillar descent. Hemimegaloencephaly is characterized by hypertrophy of whole or part of a cerebral hemisphere. Focal areas of polymicrogyria, pachygyrias, and heterotopias with focal or diffuse neuronal migration defects may be present in the affected hemisphere. Fourteen cases of children with KTS with hemimegaloencephaly have been reported, but to the best of our knowledge only four cases had the concomitant presence of Chiari I malformation [Table 1].[3],[4],[5],[6]
Table 1: Case reports of KTS with Chiari type 1 malformation

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The management of KTS is symptomatic requiring a multidisciplinary team approach. Physiotherapy and compression dressing can manage most venous malformation, but severe cases may require sclerotherapy. Sirolimus, a potent inhibitor of mTOR, has also been used successfully for the treatment of cutaneous bleeding in KTS.[2] For patients with progressive spinal deformity, the reasons can be either associated Chiari 1 malformation or pelvic tilt due to limb length discrepancy. KTS patients in whom  Chiari malformation More Details remains asymptomatic should be kept for close observation to look for progression of deformity or development of syringomyelia.

   Conclusion Top

KTS is a complex clinical entity requiring multi­disciplinary team management. As the present case demonstrates, the mechanisms of neurological involvement in KTS are yet to be evaluated in detail. Chiari 1 malformation in patients with KTS can be asymptomatic; however, close follow-up is required to look for progression of symptoms. The neurological manifestations are amenable to therapy by standard neurosurgical management.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of Interest

There are no conflicts of interest.

   References Top

Oduber CE, van der Horst CM, Hennekam RC. Klippel–Trenaunay syndrome: Diagnostic criteria and hypothesis on etiology. Ann Plast Surg 2008;60:217-23.  Back to cited text no. 1
Bessis D, Vernhet H, Bigorre M, Quéré I, Rössler J. Life-threatening cutaneous bleeding in childhood Klippel–Trenaunay syndrome treated with oral sirolimus. JAMA Dermatol 2016;152:1058-9.  Back to cited text no. 2
Valdés F, Vadillo FJ, Martínez A. [Klippel–Trénaunay syndrome and Arnold-Chiari type I malformation]. Acta Dermosifiliogr 2007;98:441-2.  Back to cited text no. 3
Torregrosa A, Martí-Bonmatí L, Higueras V, Poyatos C, Sanchís A. Klippel–Trenaunay syndrome: Frequency of cerebral and cerebellar hemihypertrophy on MRI. Neuroradiology 2000;42:420-3.  Back to cited text no. 4
Snee IA, Mazzola CA, Sikorskyj T. Chiari I malformation with Klippel–Trenaunay syndrome: Case report and review of the literature. Child’s Nerv Syst2021;37:2369-73.  Back to cited text no. 5
Zhai J, Zhong ME, Shen J, Tan H, Li Z. Kyphoscoliosis with Klippel–Trenaunay syndrome: A case report and literature review. BMC Musculoskelet Disord 2019;20:10.  Back to cited text no. 6


  [Figure 1]

  [Table 1]


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