Case report
Klippel–Trenaunay syndrome with rudimentary polydactyly Isßıl Deniz Oguz1, MD, M€ uzeyyen G€ on€ ul1, MD, Seray K€ ulc€ uC ß akmak1, MD, and € Ulker G€ ul1, MD
1 Dermatology Clinic, Ankara Numune Education and Research Hospital, Sıhhıye, Ankara, Turkey
Correspondence uz, MD Isßıl Deniz Og S ß enlik mah, Buket sok €ren Ankara 38-A/8 Kecßio Turkey 06310 E-mail: [email protected]
Introduction Klippel–Trenaunay syndrome (KTS) is a rare congenital disorder with a triad of vascular malformations, for example port wine stains, venous varicosities, and bony or soft tissue hypertrophy involving an extremity.1–3 Early diagnosis is important to avoid complications, such as thrombophlebitis, pulmonary embolism, stasis dermatitis, cutaneous ulcerations, and bleeding.1 Other abnormalities, such as polydactyly, syndactyly, clinodactyly, macrocephaly, megalencephaly, scoliosis, or spinal extradural meningeal cyst may be rarely associated with this syndrome.3–7. We report a case of a 4-year-old with KTS with rudimentary polydactyly.
Her parents were not related, and there was no family history of vascular lesions or polydactyly. On dermatological examination, a pink-red-colored, sharply demarcated, irregular bordered port wine stain that was between the distal half of the ventral aspect of the right thigh and lower edge of the patella including prepatellar
Case report A 4-year-old girl was admitted to our outpatient clinic with a pink vascular lesion on her right leg, and length and girth enlargement of the same leg. In her history, the vascular lesion was present at birth, and it enlarged parallel to the growth of the patient. Also, she had finger-like extensions of approximately 1 cm length on the lateral side of her left fifth finger and toe at birth. Her parent informed that these extensions had included nails and had amputated spontaneously one or two weeks after birth. It was learned that when she was one month old, purple-colored vascular papules millimetric in size appeared on the pink lesion, and their diameters also increased with age. There was no other history of illness. ª 2014 The International Society of Dermatology
Figure 1 A pink-red-colored, sharply demarcated, irregular bordered port wine stain and venous varicosities on the right leg International Journal of Dermatology 2015, 54, 465–467
465
466
Case report
uz et al. Og
Klippel–Trenaunay syndrome
The rudimentary fingers’ residues were seen as small skincolored papules on the ulnar site of the left fifth finger and toe (Fig. 3). On Doppler ultrasonography of the right lower extremity, superficial veins were dilated, and the walls of the dilated veins were thicker than the others. Venous thrombosis was not detected. Magnetic resonance imaging of the patient’s lower extremity could not be done because her parents did not accept it. The patient was diagnosed as KTS with clinical and ultrasonographic findings, and she was investigated for other anomalies. No other associated abnormality was detected. Laser treatment was offered for the port wine stain, and she was referred to a cardiovascular surgeon for varicose veins. Discussion
Figure 2 On the port wine stain there are many pink-purplecolored, lobulated, vascular blebs
skin was observed (Fig. 1). On the port wine stain, there were many pink-purple-colored, lobulated, soft, vascular blebs sized between 3 mm and 2 cm (Fig. 2). Venous varicosities were seen on her right leg. The length and girth of the two lower limbs were different. When the lengths of the legs were measured between spina iliaca anterior superior and the medial malleolus, her right leg was 3 cm longer than her left leg. The girths of the legs were measured from four sides: midpoint of femur; midpoint of patella; midpoint of tibia; and midpoint of ankle. There were 2 cm, 3.5 cm, 3 cm, and 3 cm differences, respectively. All of the measures were longer on the right leg.
Figure 3 The rudimentary fingers residues on the ulnar site of the left fifth finger (big picture) and toe (small picture) International Journal of Dermatology 2015, 54, 465–467
KTS is also known as nevus varicosus osteohypertrophicus.8 Diagnostic criteria of this syndrome are cutaneous vascular malformation (birthmark), superficial venous varicosity, and hyperplasia of soft tissue and bone of the affected limb.1,5,8 At least two of the three criteria must be seen for diagnosis.4,9 In our patient, all of the three criteria were present. It is thought that mesodermal abnormalities during fetal development affect angiogenesis and lead maintenance of microscopic arteriovenous communications in the limb bud.3,4,10. Persistence of the embryological vascular system would cause an augmentation of blood flow and lead to edema and hypertrophy of the bone and soft tissue of the affected extremity.3,4 Also, deep venous obstructions by fibrous bands and venous atresia may cause venous insufficiency, extremity edema, and finally an increase in the length and girth of the limb.3,4,10 Although KTS is a sporadic disease, some familial cases have been reported.3,9 Inheritance is not compatible with Mendelian pattern as it is thought to have a multifactorial inheritance.3 Three chromosomal abnormalities had been reported in three different patients with KTS.9 Twohit hypothesis may explain the occurrence of KTS. Germline mutations in a KTS gene for development of KTS are not sufficient. Somatic mutation in the same KTS gene or in a different gene leads to development of KTS features.9 Polydactyly is a common congenital anomaly. Ulnar polydactyly (postaxial polydactyly) has two types: type A has a fully formed accessory digit; and type B has a rudimentary digit, which can contain cartilage or vestigial nail apparatus.11 Inheritance may be autosomal dominant.11 Our patient’s rudimentary fingers were rudimentary digit type B, because they had not been fully formed. Some digital anomalies associated with KTS have been reported.4,5 In 1991, McGory et al. investigated the ª 2014 The International Society of Dermatology
uz et al. Og
anomalies of fingers and toes in 108 patients with KTS, and they found 126 finger and toe anomalies in 29 patients: 26 were macrodactyly, nine syndactyly, two clinodactyly, two polydactyly, one camptodactyly, and one congenital trigger finger.5 The two patients with polydactyly had postaxial polydactyly of left toes, and both had only soft tissue duplication. Both of them had vascular malformations on both of their lower limbs.5 According to their hypothesis, mesodermal and ectodermal abnormalities occurring during a 3–6 week period after fertilization during angiogenesis and development of the limb buds may cause both KTS and digital anomalies.5 Sunar et al. reported a case of a 20-year-old male with KTS who had varicose veins and cutaneous vascular nevi in both legs. He also had six digits on his left hand.4 In our patient, rudimentary digits and limb hypertrophy were on different extremities. This status may explain that etiological factors may have an effect on both angiogenesis and development of extremities because of concurrent embryological developments, such as the hypothesis of McGory et al. Also, a crossed-dissociated form of KTS has been defined in which the varicose veins, capillary malformations, and hypertrophy are present in different extremities.5 Our case may also be a sample of dissociative type KTS. Facial port wine stain, spinal arteriovenous malformations, port wine stain on arm, penile hemangioma, colon varicosities, and gingival overgrowth are other involvements associated with KTS.3,7,12–16 In our patient, no other abnormalities were detected. Complications of KTS are: thrombophlebitis; pulmonary embolism; stasis dermatitis; cutaneous ulcerations; and bleeding; and patients should be monitored for these complications.1 For vascular malformations, surgery, sclerotherapy, or laser therapy can be performed.1,17 Anticoagulant therapy or inferior vena cava filtration can be used for preventing venous thromboembolism.17 For venous insufficiency, compression therapy with an elastic garment or compression bandage should be recommended.17 We offered laser treatment for port wine stain and referred to cardiovascular surgery for varicose veins. We are presenting this case because of its rarity and coexistence with digital abnormalities. We want to remind that KTS should also be kept in mind in patients with extremity hypertrophy and vascular malformation, as early diagnosis of this syndrome is important because of its complications. References 1 Paller AS, Mancini AJ, eds. Vascular disorders of infancy and childhood. Hurwitz Clinical Pediatric Dermatology: ª 2014 The International Society of Dermatology
Klippel–Trenaunay syndrome
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17
Case report
a Textbook of Skin Disorders of Childhood and Adolescence, 4th edn. Edinburgh : Saunders, 2011: 268– 302. Choi KC, Ahn ST, Shin YH, et al. Spinal extradural meningeal cyst in Klippel-Trenaunay syndrome. J Korean Neurosurg Soc 2011; 49: 299–301. Leon Cdo A, Braun Filho LR, Ferrari MD, et al. KlippelTrenaunay syndrome: case report. An Bras Dermatol 2010; 85: 93–96. Sunar H, Halici U, Duran E. Klippel-Trenaunay syndrome associated with polydactyly. Clin Anat 2006; 19: 78–81. McGory BJ, Amadio PC, Dobyns JH, et al. Anomalies of the fingers and toes associated with KlippelTrenaunay syndrome. J Bone Joint Surg Am 1991; 73: 1537–1546. Arai Y, Takagi T, Matsuda T, et al. Myelopathy due to scoliosis with vertebral hypertrophy in KlippelTrenaunay-Weber syndrome. Arch Orthop Trauma Surg 2002; 122: 120–122. Dhamecha RD, Edwards-Brown MK. Klippel-TrenaunayWeber syndrome with hemimegalencephaly. J Craniofac Surg 2001; 12: 194–196. Dervendizi Sikova D, Pavlova LT, Vlckova Laskoska MT, et al. Naevus varicosus osteohypertrophicus. An early diagnostic approach. Adv Exp Med Biol 1999; 455: 535– 540. Wang QK. Update on the molecular genetics of vascular anomalies. Lymphat Res Biol 2005; 3: 226–233. Snow RD, Lecklitner ML. Musculoskeletal findings in Klippel-Trenaunay syndrome. Clin Nucl Med 1991; 16: 928–930. Upjohn E, Barlow R, Robson A. Rudimentary polydactyly in an adult: an unusual presentation to a dermatological surgery unit. Australas J Dermatol 2006; 47: 206–208. Schumacher M. Klippel-Trenaunay syndrome and spinal arteriovenous malformations: an erroneous association. Am J Neuroradiol 2011; 32: 76–77. Yoon TY, Kim JW, Kim MK. Klippel-Trenaunay syndrome showing hypotrophy of the affected arm. Br J Dermatol 2007; 156: 391–392. Tepeler A, Yesßilolva Y, Kılıncß A, et al. A mild and rare form of Klippel-Trenaunay syndrome presenting with urethral bleeding due to penile hemangioma. Urology 2011; 77: 463–465. Deepinder F. GI bleeding, colon varicosities, and visceral enlargement as a manifestation of Klippel-Trenaunay syndrome. Clin Gastroenterol Hepatol 2011; 9: e126– e127. Ozdemir H, Marakoglu I, Akyol M, et al. KlippelTrenaunay syndrome manifesting as gingival overgrowth and teeth agenesis. J Clin Pediatr Dent 2010; 34: 351– 354. Gloviczki P, Driscoll DJ. Klippel-Trenaunay syndrome: current management. Phlebology 2007; 22: 291–298.
International Journal of Dermatology 2015, 54, 465–467
467
This document is a scanned copy of a printed document. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material.
Klippel–Trenaunay syndrome with rudimentary polydactyly Isßıl Deniz Oguz1, MD, M€ uzeyyen G€ on€ ul1, MD, Seray K€ ulc€ uC ß akmak1, MD, and € Ulker G€ ul1, MD
1 Dermatology Clinic, Ankara Numune Education and Research Hospital, Sıhhıye, Ankara, Turkey
Correspondence uz, MD Isßıl Deniz Og S ß enlik mah, Buket sok €ren Ankara 38-A/8 Kecßio Turkey 06310 E-mail: [email protected]
Introduction Klippel–Trenaunay syndrome (KTS) is a rare congenital disorder with a triad of vascular malformations, for example port wine stains, venous varicosities, and bony or soft tissue hypertrophy involving an extremity.1–3 Early diagnosis is important to avoid complications, such as thrombophlebitis, pulmonary embolism, stasis dermatitis, cutaneous ulcerations, and bleeding.1 Other abnormalities, such as polydactyly, syndactyly, clinodactyly, macrocephaly, megalencephaly, scoliosis, or spinal extradural meningeal cyst may be rarely associated with this syndrome.3–7. We report a case of a 4-year-old with KTS with rudimentary polydactyly.
Her parents were not related, and there was no family history of vascular lesions or polydactyly. On dermatological examination, a pink-red-colored, sharply demarcated, irregular bordered port wine stain that was between the distal half of the ventral aspect of the right thigh and lower edge of the patella including prepatellar
Case report A 4-year-old girl was admitted to our outpatient clinic with a pink vascular lesion on her right leg, and length and girth enlargement of the same leg. In her history, the vascular lesion was present at birth, and it enlarged parallel to the growth of the patient. Also, she had finger-like extensions of approximately 1 cm length on the lateral side of her left fifth finger and toe at birth. Her parent informed that these extensions had included nails and had amputated spontaneously one or two weeks after birth. It was learned that when she was one month old, purple-colored vascular papules millimetric in size appeared on the pink lesion, and their diameters also increased with age. There was no other history of illness. ª 2014 The International Society of Dermatology
Figure 1 A pink-red-colored, sharply demarcated, irregular bordered port wine stain and venous varicosities on the right leg International Journal of Dermatology 2015, 54, 465–467
465
466
Case report
uz et al. Og
Klippel–Trenaunay syndrome
The rudimentary fingers’ residues were seen as small skincolored papules on the ulnar site of the left fifth finger and toe (Fig. 3). On Doppler ultrasonography of the right lower extremity, superficial veins were dilated, and the walls of the dilated veins were thicker than the others. Venous thrombosis was not detected. Magnetic resonance imaging of the patient’s lower extremity could not be done because her parents did not accept it. The patient was diagnosed as KTS with clinical and ultrasonographic findings, and she was investigated for other anomalies. No other associated abnormality was detected. Laser treatment was offered for the port wine stain, and she was referred to a cardiovascular surgeon for varicose veins. Discussion
Figure 2 On the port wine stain there are many pink-purplecolored, lobulated, vascular blebs
skin was observed (Fig. 1). On the port wine stain, there were many pink-purple-colored, lobulated, soft, vascular blebs sized between 3 mm and 2 cm (Fig. 2). Venous varicosities were seen on her right leg. The length and girth of the two lower limbs were different. When the lengths of the legs were measured between spina iliaca anterior superior and the medial malleolus, her right leg was 3 cm longer than her left leg. The girths of the legs were measured from four sides: midpoint of femur; midpoint of patella; midpoint of tibia; and midpoint of ankle. There were 2 cm, 3.5 cm, 3 cm, and 3 cm differences, respectively. All of the measures were longer on the right leg.
Figure 3 The rudimentary fingers residues on the ulnar site of the left fifth finger (big picture) and toe (small picture) International Journal of Dermatology 2015, 54, 465–467
KTS is also known as nevus varicosus osteohypertrophicus.8 Diagnostic criteria of this syndrome are cutaneous vascular malformation (birthmark), superficial venous varicosity, and hyperplasia of soft tissue and bone of the affected limb.1,5,8 At least two of the three criteria must be seen for diagnosis.4,9 In our patient, all of the three criteria were present. It is thought that mesodermal abnormalities during fetal development affect angiogenesis and lead maintenance of microscopic arteriovenous communications in the limb bud.3,4,10. Persistence of the embryological vascular system would cause an augmentation of blood flow and lead to edema and hypertrophy of the bone and soft tissue of the affected extremity.3,4 Also, deep venous obstructions by fibrous bands and venous atresia may cause venous insufficiency, extremity edema, and finally an increase in the length and girth of the limb.3,4,10 Although KTS is a sporadic disease, some familial cases have been reported.3,9 Inheritance is not compatible with Mendelian pattern as it is thought to have a multifactorial inheritance.3 Three chromosomal abnormalities had been reported in three different patients with KTS.9 Twohit hypothesis may explain the occurrence of KTS. Germline mutations in a KTS gene for development of KTS are not sufficient. Somatic mutation in the same KTS gene or in a different gene leads to development of KTS features.9 Polydactyly is a common congenital anomaly. Ulnar polydactyly (postaxial polydactyly) has two types: type A has a fully formed accessory digit; and type B has a rudimentary digit, which can contain cartilage or vestigial nail apparatus.11 Inheritance may be autosomal dominant.11 Our patient’s rudimentary fingers were rudimentary digit type B, because they had not been fully formed. Some digital anomalies associated with KTS have been reported.4,5 In 1991, McGory et al. investigated the ª 2014 The International Society of Dermatology
uz et al. Og
anomalies of fingers and toes in 108 patients with KTS, and they found 126 finger and toe anomalies in 29 patients: 26 were macrodactyly, nine syndactyly, two clinodactyly, two polydactyly, one camptodactyly, and one congenital trigger finger.5 The two patients with polydactyly had postaxial polydactyly of left toes, and both had only soft tissue duplication. Both of them had vascular malformations on both of their lower limbs.5 According to their hypothesis, mesodermal and ectodermal abnormalities occurring during a 3–6 week period after fertilization during angiogenesis and development of the limb buds may cause both KTS and digital anomalies.5 Sunar et al. reported a case of a 20-year-old male with KTS who had varicose veins and cutaneous vascular nevi in both legs. He also had six digits on his left hand.4 In our patient, rudimentary digits and limb hypertrophy were on different extremities. This status may explain that etiological factors may have an effect on both angiogenesis and development of extremities because of concurrent embryological developments, such as the hypothesis of McGory et al. Also, a crossed-dissociated form of KTS has been defined in which the varicose veins, capillary malformations, and hypertrophy are present in different extremities.5 Our case may also be a sample of dissociative type KTS. Facial port wine stain, spinal arteriovenous malformations, port wine stain on arm, penile hemangioma, colon varicosities, and gingival overgrowth are other involvements associated with KTS.3,7,12–16 In our patient, no other abnormalities were detected. Complications of KTS are: thrombophlebitis; pulmonary embolism; stasis dermatitis; cutaneous ulcerations; and bleeding; and patients should be monitored for these complications.1 For vascular malformations, surgery, sclerotherapy, or laser therapy can be performed.1,17 Anticoagulant therapy or inferior vena cava filtration can be used for preventing venous thromboembolism.17 For venous insufficiency, compression therapy with an elastic garment or compression bandage should be recommended.17 We offered laser treatment for port wine stain and referred to cardiovascular surgery for varicose veins. We are presenting this case because of its rarity and coexistence with digital abnormalities. We want to remind that KTS should also be kept in mind in patients with extremity hypertrophy and vascular malformation, as early diagnosis of this syndrome is important because of its complications. References 1 Paller AS, Mancini AJ, eds. Vascular disorders of infancy and childhood. Hurwitz Clinical Pediatric Dermatology: ª 2014 The International Society of Dermatology
Klippel–Trenaunay syndrome
2
3
4
5
6
7
8
9 10
11
12
13
14
15
16
17
Case report
a Textbook of Skin Disorders of Childhood and Adolescence, 4th edn. Edinburgh : Saunders, 2011: 268– 302. Choi KC, Ahn ST, Shin YH, et al. Spinal extradural meningeal cyst in Klippel-Trenaunay syndrome. J Korean Neurosurg Soc 2011; 49: 299–301. Leon Cdo A, Braun Filho LR, Ferrari MD, et al. KlippelTrenaunay syndrome: case report. An Bras Dermatol 2010; 85: 93–96. Sunar H, Halici U, Duran E. Klippel-Trenaunay syndrome associated with polydactyly. Clin Anat 2006; 19: 78–81. McGory BJ, Amadio PC, Dobyns JH, et al. Anomalies of the fingers and toes associated with KlippelTrenaunay syndrome. J Bone Joint Surg Am 1991; 73: 1537–1546. Arai Y, Takagi T, Matsuda T, et al. Myelopathy due to scoliosis with vertebral hypertrophy in KlippelTrenaunay-Weber syndrome. Arch Orthop Trauma Surg 2002; 122: 120–122. Dhamecha RD, Edwards-Brown MK. Klippel-TrenaunayWeber syndrome with hemimegalencephaly. J Craniofac Surg 2001; 12: 194–196. Dervendizi Sikova D, Pavlova LT, Vlckova Laskoska MT, et al. Naevus varicosus osteohypertrophicus. An early diagnostic approach. Adv Exp Med Biol 1999; 455: 535– 540. Wang QK. Update on the molecular genetics of vascular anomalies. Lymphat Res Biol 2005; 3: 226–233. Snow RD, Lecklitner ML. Musculoskeletal findings in Klippel-Trenaunay syndrome. Clin Nucl Med 1991; 16: 928–930. Upjohn E, Barlow R, Robson A. Rudimentary polydactyly in an adult: an unusual presentation to a dermatological surgery unit. Australas J Dermatol 2006; 47: 206–208. Schumacher M. Klippel-Trenaunay syndrome and spinal arteriovenous malformations: an erroneous association. Am J Neuroradiol 2011; 32: 76–77. Yoon TY, Kim JW, Kim MK. Klippel-Trenaunay syndrome showing hypotrophy of the affected arm. Br J Dermatol 2007; 156: 391–392. Tepeler A, Yesßilolva Y, Kılıncß A, et al. A mild and rare form of Klippel-Trenaunay syndrome presenting with urethral bleeding due to penile hemangioma. Urology 2011; 77: 463–465. Deepinder F. GI bleeding, colon varicosities, and visceral enlargement as a manifestation of Klippel-Trenaunay syndrome. Clin Gastroenterol Hepatol 2011; 9: e126– e127. Ozdemir H, Marakoglu I, Akyol M, et al. KlippelTrenaunay syndrome manifesting as gingival overgrowth and teeth agenesis. J Clin Pediatr Dent 2010; 34: 351– 354. Gloviczki P, Driscoll DJ. Klippel-Trenaunay syndrome: current management. Phlebology 2007; 22: 291–298.
International Journal of Dermatology 2015, 54, 465–467
467
This document is a scanned copy of a printed document. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material.
