CAPUANO P

D'ARMIENTO, MARIA

LAMBERTI A

LIGUORI M

MARTINELLI, PASQUALE

PALADINI, DARIO

TEODORO A

English

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Prenatal diagnosis and hemodynamicevaluation of Klippel–Trenaunay–WebersyndromeD. Paladini, A. Lamberti, A. Teodoro, M. Liguori, M. D’Armiento*, P. Capuano† and P. MartinelliFetal Cardiology Unit, Department of Gynecology and Obstetrics; *Department of Pathology, Federico II Universityof Naples; †Division of Obstetrics and Gynecology, Ospedale Loreto Mare, Naples, ItalyKey words: HEMANGIOMATOSIS, ULTRASOUND, LIMB HYPERTROPHY, HEART FAILURE, SOFT TISSUE DYSPLASIAABSTRACTKlippel–Trenaunay–Weber syndrome is a rare congenitalsoft-tissue anomaly which is characterized by the presenceof multiple hemangiomata, arteriovenous fistulas and limbhypertrophy. We report  the ultrasound findings  in twocases of early prenatal diagnosis at 17 and 18 weeks ofgestation. The pathogenesis of the syndrome and involve-ment of the cardiovascular system are discussed.INTRODUCTIONKlippel–Trenaunay–Weber syndrome is a rare congenitalanomaly originally described by Klippel and Trenaunay in19001 and characterized by the presence of multiple skinhemangiomata, asymmetric limb hypertrophy and arterio-venous fistulas. In the literature, several cases have beenreported in neonates but few in fetuses2–5. Yankowitz andcolleagues6 and Jorgenson and colleagues7 reported theearliest known prospective intrauterine diagnoses at 17 and19 weeks of gestation, respectively, but in the former casethere was a positive family history. To the best of ourknowledge, only Meholic and co-workers5 reported a pros-pective case in a family with no history of the disease.We report here two cases of prospective intrauterinediagnosis of Klippel–Trenaunay–Weber syndrome infamilies with negative history diagnosed at 17 and 18weeks of gestation. In the latter case, a detailed hemo-dynamic evaluation was carried out.CASE REPORTSCase 1A 21-year-old woman, gravida 2,1,0,0, with no familyhistory of congenital anomalies, was referred to our unitfor the presence of fetal right leg edema at 17 weeks ofgestation. The ultrasound examination confirmed the pres-ence of gross subcutaneous thickening involving the wholeleg from the thigh to the foot (Figure 1). The lesionextended cephalad to the right iliac fossa, where a micro-cystic hemangioma was present. Limb hypertrophy andasymmetry were also noted. No other macroscopicanomaly was found on ultrasound examination. Thepatient was counselled about the probable diagnosis ofKlippel–Trenaunay–Weber syndrome and its variable prog-nosis, and decided to have her pregnancy terminated. Atnecropsy (Figure 2), the ultrasound findings were con-firmed and, in addition, hemangiomatous lesions ofvarious sizes were found in most of the abdominal organs(intestine, liver and kidneys).Correspondence: Dr D. Paladini, Via Cimarosa 69, 80127 Naples, ItalyUltrasound Obstet Gynecol 1998;12:215–217CASE REPORT Received 18–11–97Revised 26–5–98Accepted 27–5–98215Figure 1 The right leg is shown in the picture: on the left is themulticystic hemangioma involving the whole thigh and on theright is the leg with the foot shown on a frontal plane. T, thigh; Ti,tibia; F, foot97/194 AMA: First ProofCase 2A 23-year-old woman, gravida 1,0,0,0, was referred to ourFetal Cardiology Unit because of a fetal ‘thoracic cyst’ at18 weeks of gestation. The ultrasound examinationrevealed the presence of a cystic mass of 35 mm located inthe right fetal axilla between the thorax and the right arm.Its walls were regular and its contents sonolucent (Figure3). Its lumen was seen to communicate with an enlargedsubcutaneous lymph vessel of the arm, but no flow couldbe detected by color or pulsed wave Doppler. At the level ofthe right groin, the subcutaneous layer appeared somewhatmicrocystic, with minor deformation of the cutaneous out-line. This lesion was diagnosed as a hemangioma. Duringthe same examination, clear hypertrophy of the right legwas noted.On echocardiography, normal atrioventricular andventriculoarterial connections were demonstrated. Analysisof peak velocities at the level of the atrioventricular andsemilunar valves revealed values at the upper level forgestational age. The combined cardiac output ((cross-sectional area of aortic valve × velocity time integral of thevelocity waveform) + (cross-sectional area of pulmonaryvalve × velocity time integral of the velocity waveform)× heart rate) was 282 ml/min, which is within the normalrange for gestational age according to our and other pub-lished curves8. Neither fetal hydrops nor polyhydramnioswere present.The patient was counselled about the probable diagno-sis of Klippel–Trenaunay–Weber syndrome and its progno-sis, and elected to terminate the pregnancy. She wasadmitted 1 week later and, before the abortive labor wasinduced with prostaglandins, the ultrasound scan wasrepeated. The cystic mass had not increased in size, but theinguinal hemangiomatous lesion had extended to the rightside of the fetal abdomen, where a 20-mm mass with thesame sonographic features as the inguinal lesion was pre-sent. In addition, most of the posterior aspect of the fetaltrunk showed similar hemangiomatous lesions. There wasmoderate polyhydramnios and mild pericardial effusion.The Doppler analysis of the central vessels and the calcula-tion of the combined cardiac output were repeated. Allvalues were increased and significantly above the range for19 weeks of gestation; in particular, the combined cardiacoutput had reached 350 ml/min8, leading to a diagnosis ofhigh-output cardiac failure.Postmortem examination following termination of preg-nancy confirmed the presence of gross hemangiomata ofthe trunk, the right flank and the groin, and hypertrophy ofthe right leg (Figure 4).DISCUSSIONKlippel–Trenaunay–Weber syndrome is a well-definedpathological entity which has been widely reported in thepediatric literature as a relatively benign condition, becausein most cases the hemangiomatous lesions tend to regress inthe neonatal period7,9. However, the ultimate prognosis ofthe disease depends upon the location and size of thehemangiomata which may bleed, leading sometimes to life-threatening hemorrhages. Prenatal ultrasound diagnosis isfeasible and has been described in a few cases, but in mostof these the diagnosis was retrospective2,3 or based on thepresence of a positive family history4. To our knowledge,only one case of early prospective diagnosis in a familyFigure 2 Necropsy. The hemangioma involving the entire leg andthe right part of the abdomen is evidentFigure 3 Transverse scan of the fetal thorax. The large cysticmass occupies the right axilla. M, mass; RV, right ventricle; LA,left atrium; SP, spineFigure 4 At necropsy, the cystic axillary mass (M) and thediffuse hemangiomatosis of the lower right part of the body isevident97/194Klippel–Trenaunay–Weber syndrome Paladini et al.AMA: First Proof216 Ultrasound in Obstetrics and Gynecologywith negative history has previously been reported, in a17-week fetus5.The ultrasound diagnosis of the syndrome is based uponthe association of cutaneous or subcutaneous cystic ormulticystic lesions and asymmetric limb hypertrophy5.Additional features are represented by limb edema6 andcardiac failure, ranging from isolated cardiomegaly9 tosevere hydrops4. Intrauterine ultrasound differential diag-nosis includes those conditions characterized by bodyasymmetry and/or hypertrophy such as Proteus, CHILD(congenital hemidysplasia, ichthyosiform erythrodermaand limb defects) and Beckwith–Wiedemann syndromes.The exclusion of the last condition is of the utmostimportance, because familial cases with autosomal domin-ant inheritance have recently been described10.Another important issue is the natural history ofKlippel–Trenaunay–Weber syndrome. Rapid progressionof the hemangiomatous lesions has been reported byJorgenson and colleagues7. In their case, the lesion involv-ing only one foot at 19 weeks of gestation extended in 4weeks to the entire leg. In our case, right leg hypertrophy, acystic cutaneous thoracic mass and subcutaneous involve-ment of the right inguinal region were present at 18 weeks.One week later, the following had appeared: a large cutan-eous hemangioma bulging from the right flank, extensivesubcutaneous involvement of the trunk and signs of high-output cardiac failure (pericardial effusion and high com-bined cardiac output), as was reported also by Drose andco-workers9. The occurrence of this latter phenomenon, thehigh-output cardiac failure, is likely to be due to the devel-opment of multiple arteriovenous fistulas; in fact,  onlythe rapid development of numerous arteriovenous fistulasmay explain the acute change in cardiac output and thepericardial effusion.However, postnatal regression of the hemangiomata hasbeen described in several instances. This biphasic coursewith intrauterine growth and neonatal variable regressionis similar to that of cardiac rhabdomyomata in neurofibro-matosis (von Recklinghausen’s disease). These tumors arealso reported to reach their maximum dimensions duringthe third trimester of pregnancy and to regress after birth11.It is therefore interesting to note that the two conditionsshare mesodermal origin and both  have  been classifiedamong congenital soft-tissue dysplasias12. Even though thepostnatal course of Klippel–Trenaunay–Weber syndrome iscompletely different from that of neurofibromatosis and,above all, mental retardation is absent in the former syn-drome but affects 20% of infants with neurofibromatosis,the mechanism of the reported intrauterine tumoral growthspurt may be the same for both conditions. It can bespeculated that, in these diseases, possibly on geneticgrounds, the maternal gestational hormonal milieu mightexert an exaggerated mitotic effect on selected fetal meso-dermal cellular populations, leading to the appearance ofrhabdomyomata in neurofibromatosis and hemangiomatain Klippel–Trenaunay–Weber syndrome.In conclusion, we can confirm that, in cases with nofamily history of congenital abnormalities, ultrasound canbe used to diagnose Klippel–Trenaunay–Weber syndrome.Ultrasound demonstrated the progressive nature of the syn-drome and showed that hemangiomata resulted from theformation of arteriovenous fistulas and may have had anadverse effect on cardiac function.REFERENCES1. Klippel M, Trenaunay P. Naevus variqueus osteo-hypertro-phique. Arch Gen Med 1900;185:641–722. Hatijs CG, Philip AG, Anderson GG, Mann LI. The in uteroultrasonographic appearance of Klippel–Trenaunay–Webersyndrome. Am J Obstet Gynecol 1981;139:972–43. Seod M, Santos-Ramos R, Friedman JM. Early prenatal ultra-sonic findings in Klippel–Trenaunay–Weber syndrome. PrenatDiagn 1984;4:227–304. Mor Z, Schreyer P, Weinraub Z, Hayman E, Caspi E. Non-immune hydrops fetalis associated with angioosteohyper-trophy (Klippel–Trenaunay) syndrome. Am J Obstet Gynecol1988;59:1185–65. Meholic AJ, Freimanis AK, Stucka J, Lopiccolo ML. Sono-graphic in utero diagnosis of Klippel–Trenaunay–Weber syn-drome. J Ultrasound Med 1991;10:111–146. Yankowitz J, Slagel DD, Williamson R. Prenatal diagnosis ofKlippel–Trenaunay–Weber syndrome. Prenat Diagn 1994;14:745–97. Jorgenson RJ, Darby B, Patterson R, Trimmer, KJ. Prenataldiagnosis of Klippel–Trenaunay–Weber syndrome. PrenatDiagn 1994;14:989–928. Kenny JF, Plappert T, Doubilet P, Saltzman DH, Cartier M,Zollars L. Changes in intracardiac blood flow velocities andright and left ventricular stroke volumes with gestational agein the normal human fetus: a prospective Doppler echocardio-graphic study. Circulation 1986;6:1208–169. Drose JA, Thickman D, Wiggins J, Haverkamp AB. Fetalechocardiographic findings in the Klippel–Trenaunay–Webersyndrome. J Ultrasound Med 1991;10:525–710. Jones KL. Beckwith Wiedemann syndrome. Smith’s Recogniz-able Patterns of Human Malformation, 5th edn. Philadelphia:Saunders, 1997:164–711. Paladini D, Palmieri S, Russo MG, Pacileo G. Cardiac multiplerhabdomyomatosis: prenatal diagnosis and natural history.Ultrasound Obstet Gynecol 1996;7:84–512. Martelli H, Richard S, Moczar M, Godeau G, Pfister A,Pellerin D, Vekemans M. Congenital soft tissue dysplasias: amorphological and biochemical study. Pediatr Pathol 1994;14:873–9497/194Klippel–Trenaunay–Weber syndrome Paladini et al.AMA: First ProofUltrasound in Obstetrics and Gynecology 217

Prenatal diagnosis and hemodynamic evaluation of Klippel-Trenaunay-Weber syndrome.

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Prenatal diagnosis and hemodynamic evaluation of Klippel-Trenaunay-Weber syndrome.

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