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2000-08-04-18 Klippel Trenaunay-Weber syndrome © Mejia www.thefetus.net/

Klippel Trenaunay-Weber syndrome[1]

Carlos Alberto Mejia Escobar, MD, Jorge Ramirez, MD, Oscar Medina, MD, Jaime G?mez, MD 

Introduction: This syndrome was described for the first time in 1900 and characterized by the presence of multiple skin hemangiomata, asymmetric limb hypertrophy and arteriovenous fistulas. The hypertrophy of the related bones and soft tissues produce a gigantism of the affected limb or part of the body[2],[3],[4]. The first prenatal diagnoses were reported by Hajtis[5] et al. in 1981, Seod[6] et al. in 1984, Mor[7] et al. in 1988 and Meholic[8] et al in 1991. Meizner[9] et al. and Yankowitz[10] et al. reported the earliest known prospective intrauterine diagnosis at 14 and 17 weeks respectively.

Synonyms: Klippel-Trenaunay syndrome, Angioosteohypertrophy syndrome.

Incidence: Rare.

Etiology: The pattern of inheritance for this syndrome is unknown and this it etiology has not yet been determined. However, Happle[11] suggested a paradominant inheritance. Heterozygous individuals for a single gene defect are phenotypically normal. The trait is only expressed when a somatic mutation occurs in the normal allele at an early stage for the embryogenesis. The embryo is then a mosaic of homozygous or heterozygous cell lines for the mutation. This explain the patchy distribution of the defect11. Studies by Servelle et al. have showed atresia of the venous system causing venous stasis, varicosities, edema and limb elongation[12]. Baskerville et al. proposed a generalized mesodermal abnormality during fetal development affecting angiogenesis and leading to maintenance of microscopic arteriovenous communications in the limb bud which results in varicosities and hypertrophy[13].

Ultrasound diagnosis: Diagnosis has been made at as early as 14 weeks gestation and is based upon the association of cutaneous or subcutaneous cystic or multicystic lesions and marked enlargement of the soft tissues of a limb or other part of the fetal body.

Commons findings include:[14],[15]

Multiple cutaneous hemangiomata of complex texture and having both anechoic and echogenic areas, that may involve any part of the body mainly single lower extremity, buttocks, abdomen or torso and vary from simple varicosities to cavernous hemangiomata. They are of unilateral predominance but bilateral distribution is not rare.

Limb hypertrophy secondary to vascular hamartoma. A single extremity almost always is compromised and not necessarily coincides with the hemangiomata area.

Long bone asymmetry with the affected limb being longer than other contralateral bone. 

Occasional findings include:

  1. Extremities: Arteriovenous fistulas and lymphangiectasias.
  2. Hands and feet: Syndactily, polydactily and macrodactily.
  3. Face: Asymmetric facial hypertrophy, hemangiomata.
  4. Brain: Calcifications, macrocephaly.
  5. Eyes: Cataracts.
  6. Visceral involvement visceromegaly, ascites, hemangiomata of urinary and gastrointestinal system, pleura and mesentery.
  7. Cardiac: Cardiac failure ranging from isolated cardiomegaly to severe hydrops.
  8. Haematologic: Kasabach- Merrit syndrome of thrombocytopenia due to platelet consumption within the haemangioma[16]

Case:

A 17 year old woman, primigravida, with no family history of congenital anomalies was referred for the presence of fetal right leg edema at 20 weeks gestation. This  fetus was scanned at 28 and 32 weeks. What is the anomaly or syndrome called ?

The legs:

  

 

 

The abdomen

The kidneys

 

The chest

The face

The baby after delivery. Note the hemihypertrophy and the hemangiomas,

  

 

Differential diagnosis:

1.                  Proteus syndrome. Characterized by asymmetric focal overgrowth, subcutaneous tumors and hemihypertrophy.

2.                  Cystic hygroma/Lymphangioma. Abnormalities of the lymphatic vessels characterized by cyst within the soft tissues usually in the nuchal region.

3.                  Sacrococcygeal teratoma. Tumors that originate from any of the three germinal layers, are solid, cystic or complex, have a disorganized appearance and can be very vascular.

4.                  CHILD. Congenital hemidysplasia, icthyosiform erythroderma and limb defects.

5.                  Beckwith Wiedeman syndrome. Characterized by gigantism in utero, macroglossia, omphalocele and renal abnormalities. 

Recurrence risk: Probably none, although some cases could be an autosomal dominance inheritance[17]. There is a relationship between a single defect on either chromosome 5q or p11 and this syndrome[18]. Aelvoet et al suggested that Klippel-Trenaunay-Weber syndrome can have a multifactorial inheritance pattern in some cases, with a range of vascular malformations seen in affected families[19].

Natural history and prognosis: The ultimate prognosis depends on the location and size of the hemangiomata, which may bleed leading to life-threatening hemorrhages. In literature, there are descriptions of cases in which a lesion involving one foot had extended to entire leg 4 weeks later [20]. In another case, right leg hypertrophy and cystic cutaneous thoracic mass were present at 18 weeks and one week later, extensive subcutaneous involvement of the trunk and signs of high-output cardiac failure had appeared15. This latter phenomenon is likely to be due to the development of multiple arteriovenous fistulas[21].

Postnatal regression of the hemangiomata has been described in several instances. This is a biphasic course with intrauterine growth and neonatal variable regression15. The patients rarely need amputation, except if there are exaggerated gigantism or coagulation complications. One should always look for hemangiomata in viscera, brain, eyes and other areas.

Removal of the mixed arteriovenous hemangiomata by desarticulation of the involved limb aid in stabilization of the neonate’s cardiovascular status.

Reference

[2] Berry SA, Peterson C, Mize W, Bloom K, Zachary C, Blasco P, Hunter D. Klippel Trenaunay syndrome. Am J Med Genet 1998 Oct 2:79 (4):319-326

[3] Jacob AG, Driscoll DJ, Shaughnessy WJ, Stanson AW, Clay RP, Gloviczki P. Klippel Trenaunay syndrome: spectrum and management. Mayo Clinic Proc 1998 Jan;73(1):28-36.

[4] Jones LK. Klippel Trenaunay Weber syndrome. In: Smith"s Recognizable Patterns of Human Malformations. 5th edn, Philadelphia, Saunders, 1988, p. 512-513.

[5] Hatjis CG, Philip AG, Anderson GG, Mann LI. The in utero ultrasonographic appearance of Klippel-Trenaunay-Weber syndrome. Am J.Obstet.Gynecol., 1981, 139, 972-974.

[6] Seod M, Santos-Ramos R, Friedman JM. Early prenatal ultrasonographic findings in Klippel Trenaunay Weber syndrome. Prenat Diag 1984;4;227-30.

[7] Mor Z, Schreyer P, Weinraub Z, Hayman E, Caspi E. Non-inmune hydrops fetalis associated with angioosteohypertrophy (Klippel Trenaunay) syndrome. Am J Obstet Gynecol 1988;59:1185-6

[8] Meholic AJ, Freimanis AK, Stucka J, Lo Piccolo ML. Sonographic in utero diagnosis of Klippel Trenaunay Weber syndrome. J.Ultrasound Med., 1991. 10, 111-114.

[9] Meizner I, Rosenak D, Nadjari M, Naor E. Sonographic diagnosis of Klippel Trenaunay Weber syndrome presenting as a sacrococcygeal mass at 14 to 15 weeks" gestation. J. Ultrasound Med 13:901-904, 1994

[10] Yankowitz J, Slagel DD, Williamsom R. Prenatal diagnosis of Klippel-Trenaunay Weber syndrome by ultrasound. Prenat.Diagn., 1994, 14, 745-749.

[11] Happle R. Mosaicism in the human skin. Understanding the patterns and mechanisms. Arch Dermatol 1993 Nov; 129.

[12] Servelle M. Klippel and Trenaunay syndrome. 768 operated cases. Ann. Surg., 1985, 201, 365-373.

[13] Baskerville PA, Ackroyd JS, Browse NL. The etiology of the Klipplel Trenaunay syndrome. Ann. Surg., 1985, 202, 624-627.

[14] Benacerraf BR.  Klippel Trenaunay Weber syndrome. Ultrasound of fetal syndromes.  1st ed. Churchill Livingstone. 1998, 225-227.

[15] Paladini D, Lamberti A, Teodoro A, Liguori M, D"Armiento M, Capuano P, Martinelli P. Prenatal diagnosis and hemodynamic evaluation of Klippel Trenaunay Weber syndrome. Ultrasound Obstet Gynecol 1998 Sep;12(3):215-7.

[16] Christenson L, Yankowitz J, Robinson R. Prenatal diagnosis of Klippel Trenaunay Weber syndrome as a cause for in utero heart failure and severe postnatal sequelae. Prenat Diag., 17:1176-1180, 1997.

[17] Ceballos-Quintal JM, Pinto-Escalante D, Castillo-Zapata I. A new case of Klippel Trenaunay Weber syndrome: evidence of autosomal dominant inheritance. Am J Med Genet 1996 Jun 14;63(3):426-7.

[18] Whelan AJ, Watson MS, Porter FD, Steiner RD. Klippel Trenaunay Weber syndrome associated with a 5:11 balanced translocation. Am J Med. Genet. 59: 492-494, 1995.

[19] Aelvoet GE, Jorens PG, Roelen IM. Genetic aspects of the Klippel Trenaunay syndrome. Br.J Dermatol., 1992, 126, 603-607.

[20] Jorgenson RJ, Darby B, Patterson R, Trimmer KJ. Prenatal diagnosis of Klippel Trenaunay Weber syndrome. Prenat Diag. 1994,14:989-92.

[21] Drose JA, Thickman D, Wiggins J, Haverkamp AB. Fetal echocardiographic findings in the Klippel Trenaunay Weber syndrome. J Ultrasound Med 1991;10:525-7

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