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Adv Biomed Res 2017,  6:27

Proteus Syndrome with Arteriovenous Malformation

1 Department of Dermatology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
2 Psychodermatology, Psychosomatic Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

Date of Web Publication07-Mar-2017

Correspondence Address:
Atefeh Sadat Kamali
Department of Dermatology, Isfahan University of Medical Sciences, Isfahan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2277-9175.201684

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Proteus syndrome is a rare sporadic disorder that appears with localized macrosomia, congenital lipomatosis, and slow flow vascular malformations, connective tissue nevus, and epidermal nevus. There are usually some manifestations at birth. The vascular abnormalities that have been reported in Proteus syndrome are capillary and slow flow venous malformation. We report a case of a 10-year-old boy with confirmed Proteus syndrome characterized by high flow vascular malformation (arteriovenous [AV] malformation) unlike the usual vascular malformations seen in this syndrome. This case adds a new perspective to the established clinical findings of the Proteus syndrome.

Keywords: Capillary malformation, Proteus syndrome, vascular malformation

How to cite this article:
Asilian A, Kamali AS, Riahi NT, Adibi N, Mokhtari F. Proteus Syndrome with Arteriovenous Malformation. Adv Biomed Res 2017;6:27

How to cite this URL:
Asilian A, Kamali AS, Riahi NT, Adibi N, Mokhtari F. Proteus Syndrome with Arteriovenous Malformation. Adv Biomed Res [serial online] 2017 [cited 2023 Feb 8];6:27. Available from:

  Introduction Top

Proteus syndrome, a rare sporadic disorder as asymmetrical overgrowth of body parts, was first described in 1983.[1] It has been called a hamartoneoplastic disease and presented with exostosis, cranial hyperostosis, verrucous epidermal nevus, vascular malformations, and lipoma. The cardinal features are enlarged hands and feet, raised pigmented nevus, hemihypertrophy, subcutaneous masses, skull abnormalities and visceral abnormalities, and accelerated growth. The most characteristic signs are cerebriform overgrowth of the soft tissues of the palms or soles. The vascular lesions may be extensive capillary malformations or more complex combined capillary-venous-lymphatic malformations.[1],[2],[3],[4],[5],[6],[7] Since Proteus syndrome is characterized by a constellation of signs and symptoms, for the clinical diagnosis, general and specific criteria have been proposed [Table 1].[8],[9] Few reports are available in the literature for the presentation of arteriovenous (AV) malformation in this syndrome. We report a case of Proteus syndrome in a patient presented with AV malformation.{Table 1}

  Case Report Top

We report a case of a 10-year-old boy who was referred to Alzahra hospital, supervised by Isfahan University of Medical Sciences in July 2010 due to vesiculobulous lesions [Figure 1]. This patient was born as a full term neonate through vaginal delivery without any perinatal problems. On the first pediatric visit, there was no significant abnormality. Except an episode of hospitalization due to gastroenteritis and repair of inguinal herniation he was otherwise healthy until the 14th month after birth. At this time, his parents found the evolution of vesiculobollous lesions on his right buttock. The hitopathologic examination of the lesion following surgical resection was compatible with hemangiolymghanioma. However, the lesions had recurred on his right buttock and right thigh as hemorrhagic vesiculobollous lesions when he was presented to our dermatology clinic. The lesions tore easily on palpation and the scar formation was seen in his buttock. The biopsy from the lesions demonstrated lymphangioma circumscriptum. On physical examination, two other giant purple palpable plaques in the left hemi trunk and the ipsilateral flank [Figure 2] of which magnetic resonance imaging (MRI) showed AV malformation that were discovered. Apart from these vascular lesions, macrodactyly of the third toe on both feet [Figure 3a] and [Figure 3b] and kyphoscoliosis was obvious. On detailed inquiry, it was revealed that at 4 years of age, the third toes had been growing. This local gigantism caused problems in his wearing shoes and walking when he was 8 years old.
Figure 1: Vesiculobulous lesions in right buttock

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Figure 2: Ateriovenous malformation in left flank

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Figure 3a: Big toe

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Figure 3b: Its radiographic picture

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  Discussion Top

Proteus syndrome is a rare sporadic disease characterized by asymmetrical overgrowth of any part of the body, exostosis, cranial hyperostosis, verrucous epidermal nevi, vascular malformations, and lipoma-like hamartomas. The vascular lesions are capillary malformations or combined capillary-venous-lymphatic malformations.[1],[2] There is no definite genetic inheritance, although tumor suppressor gene phosphatase and tensin homolog (PTEN) tumor suppressor gene abnormalities have been described in cases of the syndrome.[10] The somatic motation of AKT1 was detected in 90% of patients. There are usually some manifestations at birth.[1] In our case, the patient had disproportionate overgrowth of limbs, skeletal abnormalities (feet), and vascular malformations (AV malformation and lymphangioma). Taken together, our case fulfilled the general criterion of harboring Proteus syndrome. The vascular abnormalities that have been reported in Proteus syndrome are capillary and slow flow venous malformation; however, no AV malformation was observed in our patient. Our case had had inguinal herniation in infancy not reported in Proteus syndrome. By comparison, exostosis, cranial hyperstosis, verrucous epidermal nevus, connective tissue nevus, lipoma, visceral, dental, and eye abnormalities were not seen in our patient. Due to the fact that Proteus syndrome is a sporadic disease in the category of mosaicsism disorders, attempts at discovering other possible mutations or making bridges between clinical findings and known gene mutations (PTEN) continue. In other words, this case adds a new perspective to the established clinical findings of Proteus syndrome. Due to the varying features of this syndrome, a multidisciplinary approach by consultation with a vascular surgeon and an orthopedist was requested.

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  References Top

Khangembam CB, Karunanithi S, Sharma P, Agarwal KK, Singhal A, Dhull VS, et al. Proteus syndrome: A case report with bone scintigraphy findings. Diagn Interv Radiol 2013;19:240-3.  Back to cited text no. 1
Lindhurst MJ, Sapp JC, Teer JK, Johnston JJ, Finn EM, Peters K. A mosaic activating mutation in AKT1 associated with the proteus syndrome. N Engl J Med 2011;365:611-9.  Back to cited text no. 2
Viljoen DL, Saxe N, Temple-Camp C. Cutaneous manifestations of the Proteus syndrome. Pediatr Dermatal 1988;5:14-2l.  Back to cited text no. 3
Neylon OM, Werther GA, Sabin MA. Overgrowth syndromes. Curr Opin Pediatr 2012;24:505-11.  Back to cited text no. 4
Mirastschijski U, Altmann S, Lenz-Scharf O, Muschke P, Schneider W. Syndromes with focal overgrowth in infancy: Diagnostic approach and surgical treatment. J Plast Surg Hand Surg 2012;46:45-8.  Back to cited text no. 5
Clark RD, Donnai D, Rogers J, Cooper J, Baraitser M. Proteus syndrome: An expanded phenotype. Am J Med Genet 1987;27:99-117.  Back to cited text no. 6
Darling NT, Bisecker GL. Progressive overgrowth of the cerebriform connective tissue nevus in patients whit proteus syndrome. J Am Acad Dermatol 2010;63:799-804.  Back to cited text no. 7
Biesecker LG, Happle R, Mulliken JB, Weksberg R, Graham Jr JM, Vilijoen DL. Proteus syndrome: Diagnostic criteria, differential diagnosis, and patient evaluation. Am J Med Genet 1999;84:389-95.  Back to cited text no. 8
Turner JT, Cohen MM Jr, Biesecker LG. Reassessment of the Proteus syndrome literature: Application of diagnostic criteria to published cases. Am J Med Genet A 2004;130:111-22.  Back to cited text no. 9
Zhou X, Hampel H, Thiele H, Gorlin RJ, Hennekam RC, Parisi M, et al. Association of germline mutation in the PTEN tumour suppressor gene and Proteus and Proteus-like syndromes. Lancet 2001;358:210-1.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3a], [Figure 3b]

  [Figure 3a]

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