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Table of Contents   
ORIGINAL ARTICLE
Year : 2023  |  Volume : 28  |  Issue : 5  |  Page : 387-391
 

Fetal klippel–Trenaunay–Weber syndrome: Antenatal diagnosis and postnatal management


1 Department of Maternal and Reproductive Health, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
2 Department of Pediatric Surgical Superspecialities, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
3 Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Date of Submission04-Dec-2022
Date of Decision01-Mar-2023
Date of Acceptance21-Mar-2023
Date of Web Publication05-Sep-2023

Correspondence Address:
Mandakini Pradhan
Department of Maternal and Reproductive Health, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow - 226 014, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jiaps.jiaps_170_22

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   Abstract 


Context: Klippel–Trenaunay–Weber syndrome (KTWS) is a rare disease characterized by a triad of venous malformations, vascular skin nevus and asymmetric hypertrophy of bone and soft tissue. The spectrum of disease in utero varies from asymptomatic nevus flammeus to life threatening complications like Kasabach–Merritt phenomena.
Aim: The aim of this study was to review our experience of antenatal diagnosis of KTWS and it's postnatal management.
Settings and Design: This was a retrospective observational study of all pregnant women who were antenatally diagnosed with KTWS and postnatally confirmed at a tertiary care center in north India between 2012 and 2021.
Subjects and Methods: The electronic medical records were reviewed and data were collected regarding demographic information, obstetric history, clinical presentation, sonographic findings, mode of delivery, fetal outcome, and follow-up.
Results: During the study period, four fetuses were diagnosed with KTWS on sonography. Three women were multigravida whereas one was a primigravida. Two women opted for medical termination of pregnancy and one each had liveborn child and an intra-uterine fetal death. KTWS was confirmed in all cases. The liveborn child underwent treatment for the vascular malformation and is alive at 4 years of age.
Conclusions: This study attempts to add onto the available literature regarding the spectrum of prenatal presentations of KTWS. It emphasizes the importance of prenatal diagnosis and follow-up of the fetus/neonate.


Keywords: Antenatal diagnosis, Klippel–Trenaunay–Weber syndrome, postnatal outcome, sonography


How to cite this article:
Singh N, Mandelia A, Nigam N, Yadav S, Pradhan M. Fetal klippel–Trenaunay–Weber syndrome: Antenatal diagnosis and postnatal management. J Indian Assoc Pediatr Surg 2023;28:387-91

How to cite this URL:
Singh N, Mandelia A, Nigam N, Yadav S, Pradhan M. Fetal klippel–Trenaunay–Weber syndrome: Antenatal diagnosis and postnatal management. J Indian Assoc Pediatr Surg [serial online] 2023 [cited 2023 Dec 4];28:387-91. Available from: https://www.jiaps.com/text.asp?2023/28/5/387/385141





   Introduction Top


Klippel–Trenaunay– Weber syndrome More Details (KTWS) is a rare disease with an incidence of one in 27,500 newborns. It is characterized by a triad of venous malformations, vascular skin nevus and asymmetric hypertrophy of bone and soft tissue.[1],[2] Presence of two of the three main signs confirms the diagnosis.[3] The spectrum of disease in utero varies from asymptomatic nevus flammeus and circumferential hypertrophy of one limb to polyhydramnios, macrocrania, ventriculomegaly, and hepatomegaly. Sometimes it can lead to life threatening complications like coagulopathy, high-output cardiac failure, and nonimmune hydrops fetalis.[4],[5],[6] Prenatal diagnosis of KTWS is difficult and is scarcely reported in published literature. The aim of this study was to review of our experience of antenatal diagnosis and postnatal management of KTWS.


   Subjects and Methods Top


This was a retrospective observational study of all pregnant women who were antenatally diagnosed with KTWS at a tertiary care institute of north India between 2012 and 2021. The inclusion criteria included diagnosis of KTW antenatally on sonography which was confirmed by diagnostic criteria either postnatally on imaging or on fetal autopsy. Patients not meeting the diagnostic criteria for KTWS antenatally or postnatally were excluded. The electronic medical records were reviewed and data were collected regarding demographic information, obstetric history, clinical presentation, sonographic findings, mode of delivery, fetal outcome, and follow-up. The data were reviewed and results have been described. The study was approved by Institutional Ethics Committee (IEC code: 2021-147-IP-EXP-39).


   Results Top


During the study period, four pregnant women were diagnosed with KTWS in the fetus on sonography. The details of each case are as follows:

Case 1

A 26-year-old G3P1011 was referred at 39 weeks gestation for fetal growth restriction. The couple were nonconsanguineous with no significant family or past history. She was normotensive and no other maternal cause of fetal growth restriction was identified. Ultrasound (USG) revealed an asymmetrically growth restricted fetus with numerous subcutaneous sonolucent multiloculated cystic lesions in the right lower limb, involving the whole of thigh to about two centimeters below the tibial condyle. Femur length on both sides was equal. The circumference of the right thigh was twice that of the left thigh. Color Doppler was set at the lowest frequency to detect low velocity blood flow. However, the lesion did not show any vascularity except at the peripheral areas [Figure 1]a. Umbilical artery Doppler was normal and middle cerebral artery peak systolic velocity (MCAPSV) was found to be at 1.21 MoMs for that gestation. A prenatal diagnosis of KTWS was made based on USG findings and the prognosis of the baby was explained. A female child was delivered by vaginally at 40 weeks weighing 2.6 kg with an APGAR score of 7 and 9 at 1 and 5 min of birth, respectively.
Figure 1: (a) USG image (2D) of fetal thigh showing multiple sonolucent areas in subcutaneous plane (bold arrows). Femur bone is marked with yellow arrow. (b) Clinical image of the new born showing diffuse cystic swelling involving the right thigh and gluteal region. The left lower limb is normal. (c) Contrast enhanced MRI of right lower limb showing a large cystic multiseptated lesion in subcutaneous and intramuscular plane of right lower limb with extension into gluteal region and delayed contrast enhancement. (d) Suggestive of a low flow vascular malformation. USG: Ultrasound, MRI: Magnetic resonance imaging

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On examination, facial features were normal. There was a diffuse cystic swelling in right lower limb extending from the thigh including the gluteal region along the entire thigh and up to three centimeters below the knee joint and involving the joint itself. The overlying skin did not have apparent discoloration. There were no visible dilated veins or varicosities over the swelling [Figure 1]b. It was compressible but not reducible. There was no local rise of temperature and no pulsation was palpable. The peripheral pulses-popliteal, posterior tibial and dorsalis pedis were palpable and equal in both lower limbs. The left lower limb was normal with no visible swelling. Contrast enhanced magnetic resonance imaging of right lower limb at 25 days of age showed a large cystic multiseptated lesion in subcutaneous and intramuscular plane of right lower limb with extension into gluteal region and delayed contrast enhancement, suggestive of a low flow vascular malformation. No arterial feeders, draining veins or intraosseous extension was seen [Figure 1]c and [Figure 1]d. The baby underwent multiple sessions of image guided sclerotherapy with sodium tetradecyl-sulfate between 6 and 18 months of age. The lesion responded well and significantly reduced in size. The child is now 4-year-old with near normal lower limb appearance and mobility with small residual lesion on imaging.

Case 2

A 25year old primigravida presented for a level II scan in our department at 18 weeks five days gestation. Ultrasound examination revealed a single live fetus with a large multiloculated cystic mass of three centimetres surrounding the right femoral bone along its entire length. The mass showed low resistance vascularity on colour doppler [Figure 2]a. Though femur length of both limbs was equal, there was increased soft tissue thickness on the affected side. Middle cerebral artery flow showed evidence of fetal anemia and cardiothoracic ratio was 65% suggestive of cardiomegaly, a sign of impending heart failure. A diagnosis of KTWS was made. The patient was counselled about the prognosis and the patient opted for termination of pregnancy. Abortus was a male fetus of 450 grams with a large soft cystic mass of right thigh extending from inguinal crease up to the knee joint. The autopsy findings corroborated with antenatal USG findings and the diagnosis was confirmed on histopathology [Figure 2]b.
Figure 2: (a) USG image showing both fetal thighs in longitudinal axis. Right thigh, closer to the USG probe, has multiple sonolucent areas and is markedly hypertrophied as compared to left thigh (arrow head). Color Doppler shows negligible flow in sonolucent areas (white arrow). (b) Clinical photograph of abortus showing the lesion in the right thigh (black arrow). Inset: submuscular plane (muscle plane showed by red arrow) shows a hemangioma with variable-sized vascular spaces (yellow star), lined by bland endothelial cells (H and E, ×200). USG: Ultrasound

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The patient was followed up in her next pregnancy for antenatal care. Pregnancy was uneventful and the fetus did not have any congenital malformation. She delivered a healthy female child at term which is alive and well at 6 years of follow-up.

Case 3

A 33-year-old G3P2002 was referred at 23 weeks of gestation in view of swelling of the left foot. USG showed a single live intrauterine fetus with hypertrophy of left leg extending from the groin to the foot. There were no associated malformations of other systems. Bilateral femur, tibia, fibula and foot length were corresponding for the gestational age and femur foot ratio was normal. There were multiple sonolucent cystic areas in the subcutaneous region of the left leg in its entirety with low level blood flow on color Doppler. Fetal MCA PSV was <1.5 MoM for the gestational age. The couple was counseled regarding the diagnosis and fetal prognosis was explained by the multidisciplinary team involving Maternal Fetal Medicine specialist, pediatric surgeon and neonatologist. The patient opted for termination of pregnancy. Postdelivery examination of abortus confirmed the antenatal diagnosis on gross examination and histopathology.

Case 4

A 36-year-old female, G5P4004, was referred to our department at 31 weeks of gestation for hydrops fetalis. USG showed a right sided lower limb hypertrophy with multiple sonolucent cystic areas extending over the right thigh and two third of lower leg. There were multiple sonolucent cystic areas with low level blood flow on color Doppler. Fetus also had ascites, pericardial effusion and skin edema suggestive of fetal hydrops [Figure 3]. Fetal MCAPSV was at 1.7 MoM and there was moderate polyhydramnios. She presented with preterm labor at 32 weeks 5 days with intrauterine fetal demise. A fresh stillborn male child of 2400 g was delivered vaginally. On gross examination there was marked hemihypertrophy of the right leg. Antenatal findings were confirmed postnatally.
Figure 3: USG images of the fetus showing (a) hypertrophied right leg in longitudinal plane. (b) Comparison of both fetal thighs in transverse axis shows the circumference of right thigh to be twice of left thigh which was normal. (c) Color Doppler (velocity range 8 cm/s) showing no blood flow in cystic areas (bold arrows). (d) Fetal abdomen in transverse axis shows fetal ascites (yellow arrow). USG: Ultrasound

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   Discussion Top


KTWS is a rare entity first described by Klippel and Trenaunay in 1900. In 1907, Weber added the findings of arteriovenous malformations to it thus giving the name to the syndrome as we know it today. Since then, numerous cases have been reported but majority are in postnatal life. Prenatal diagnosis of this condition has been published in <50 cases. In spite of being a benign growth, its extent of involvement is large. The challenge in its antenatal diagnosis is that it can be a small cutaneous and subcutaneous lesion to start with and can be missed prenatally. On the contrary, sometimes, it can develop early, grow fast and lead to extensive hemangioma complicated by thrombocytopenia and consumptive coagulopathy, commonly known as Kasabach–Merritt phenomena which can lead to cardiac failure and hydrops fetalis making the fetal prognosis dismal as seen in our fourth case.

Most cases of KTWS occur sporadically though familial cases have also been reported.[7] Most cases are caused due to postzygotic somatic mutations in the phosphatidylinositol-4, 5-bisphospate 3-kinase, catalytic subunit alpha (PIK3CA) gene at the long arm of chromosome three. And hence, it has been proposed to label it as a member of the PIK3CA-related overgrowth spectrum.[8] In an isolated case, a mother affected with KTWS had two pregnancies affected with fetal KTWS indicating its autosomal dominant type of inheritance.[9]

The timing of diagnosis of KTWS can vary from as early as 14 weeks to as late as term fetus. Most commonly, KTWS is diagnosed in late second or third trimester as was also seen in two of our three cases. The earliest prenatal description was made by Meizner et al. at 14 weeks.[10]

The syndrome can be identified on prenatal USG by isolated limb hypertrophy, usually lower limb, with either no flow in case of lymphatic malformation or very low velocity blood flow in case of capillary and venous malformation. Additional features are represented by limb edema and cardiac failure, ranging from isolated cardiomegaly to hydrops. The presenting feature in our first three cases was limb hypertrophy and in fourth case was hydrops fetalis. Fetal hydrops and fetal anemia as seen in our fourth case can be attributed to Kasabach–Merritt syndrome leading to consumptive coagulopathy and high output cardiac failure.[11] Fetal hydrops could be absent at the time of diagnosis in some cases and can appear later due to cardiac failure; hence, the fetus should be followed up at regular intervals to look for the same. This will also help in deciding the time and mode of delivery.

Diagnosis of KTWS is mainly made clinically in early childhood. Most common site of affection is leg and there is no gender preponderance. Its clinical presentation in postnatal life varies from minimally symptomatic disease to life-threatening bleeding and embolism. The clinical spectrum includes two major group of anomalies – congenital vascular malformations (capillary, venous and/or lymphatic) and disturbed growth (bone/soft tissue). Other associated features include limb abnormalities (polydactyly, syndactyly, camptodactyly, ectrodactyly); positional limb defects - scoliosis, hip dislocation, talipes.[4] As reported by Samuel et al and Jacob et al in their study, 85% of patients had unilateral, 12.5% had bilateral and 2.5% had crossed bilateral involvement. 10% of patients had both upper and lower limb involvement.[12],[13] In our series also, all four fetuses had unilateral lower limb affection, right sided in three and left sided in one.

The other differential diagnosis of asymmetrical limb growth includes Proteus syndrome (characterized by gyriform changes of plantar surface of feet), Beckwith Wiedemann syndrome (generalized overgrowth), CHILD syndrome, Milroy's disease, soft tissue sarcomas, cystic hygromas and lymphangiomas. Parkes–Weber syndrome is clinically similar to KTWS except that in the former arteriovenous fistulas are detected. Prenatal diagnosis is important for determining the prognosis of the fetus, counseling of the prospective parents, help them make an informed choice regarding continuation or termination of pregnancy, choosing the place of delivery and giving them time for financial arrangements for treatment of neonate, if required. In a series by Peng et al., the reported rate of Kasabach–Merritt syndrome was 36.36% and neonatal mortality rate was 45.45%.[14] In our series, two cases was diagnosed in second trimester, one at 18 weeks and another at 23 weeks; the couples opted for termination of pregnancy whereas the third case was diagnosed at term and hence the couple were counseled, institutional delivery was performed and definitive management of the neonate was done. The fourth fetus presented with nonimmune hydrops fetalis and a definite diagnosis helped in pinpointing the cause before intra uterine fetal death.


   Conclusion Top


Treatment of neonates affected with KTWS depends upon the clinical features and is individualized. Surgical debulking, sclerotherapy, compression stockings for varicosities, corrective surgeries for associated bony malformations, and symptomatic approach for any complications like ulcers, infections, discolorations has been described.

This study attempts to add onto the available literature regarding the spectrum of prenatal presentations of KTWS ranging from early detection, nonimmune hydrops fetalis and fetal death to late detection and possible postnatal management. It emphasizes the importance of prenatal diagnosis and follow-up of the fetus/neonate. Counseling of the prospective parents by a multidisciplinary team involving the obstetrician, pediatrician, and pediatric surgeon helps in better comprehension of the disease by the parents and making an informed choice, less dropout rate, and better neonatal outcome.

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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
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
    
2.
Lindenauer SM. The Klippel-Trenaunay syndrome: Varicosity, hypertrophy and hemangioma with no arteriovenous fistula. Ann Surg 1965;162:303-14.  Back to cited text no. 2
    
3.
Reyes Puentes LM, Fuentes Camargo MJ, Perez Martinez C. Diagnostico prenatal ecografco del sindrome KlippelTrenaunay-Weber: A proposito de un caso. Rev Cien Med 2010;14:656-61.  Back to cited text no. 3
    
4.
Zoppi MA, Ibba RM, Floris M, Putzolu M, Crisponi G, Monni G. Prenatal sonographic diagnosis of Klippel-Trénaunay-Weber syndrome with cardiac failure. J Clin Ultrasound 2001;29:422-6.  Back to cited text no. 4
    
5.
Mor Z, Schreyer P, Wainraub Z, Hayman E, Caspi E. Nonimmune hydrops fetalis associated with angioosteohypertrophy (Klippel-Trenaunay) syndrome. Am J Obstet Gynecol 1988;159:1185-6.  Back to cited text no. 5
    
6.
Drose JA, Thickman D, Wiggins J, Haverkamp AB. Fetal echocardiographic findings in the Klippel-Trenaunay-Weber syndrome. J Ultrasound Med 1991;10:525-7.  Back to cited text no. 6
    
7.
Wang Q, Timur AA, Szafranski P, Sadgephour A, Jurecic V, Cowell J, et al. Identification and molecular characterization of de novo translocation t(8;14)(q22.3;q13) associated with a vascular and tissue overgrowth syndrome. Cytogenet Cell Genet 2001;95:183-8.  Back to cited text no. 7
    
8.
Vahidnezhad H, Youssefian L, Uitto J. Klippel-Trenaunay syndrome belongs to the PIK3CA-related overgrowth spectrum (PROS). Exp Dermatol 2016;25:17-9.  Back to cited text no. 8
    
9.
Jorgenson RJ, Darby B, Patterson R, Trimmer KJ. Prenatal diagnosis of the Klippel-Trenaunay-Weber syndrome. Prenat Diagn 1994;14:989-92.  Back to cited text no. 9
    
10.
Meizner I, Rosenak D, Nadjari M, Maor E. Sonographic diagnosis of Klippel-Trenaunay-Weber syndrome presenting as a sacrococcygeal mass at 14 to 15 weeks' gestation. J Ultrasound Med 1994;13:901-4.  Back to cited text no. 10
    
11.
Tanaka K, Miyazaki N, Matsushima M, Yagishita R, Izawa T, Tanigaki S, et al. Prenatal diagnosis of Klippel-Trenaunay-Weber syndrome with Kasabach-Merritt syndrome in utero. J Med Ultrason (2001) 2015;42:109-12.  Back to cited text no. 11
    
12.
Samuel M, Spitz L. Klippel-Trenaunay syndrome: Clinical features, complications and management in children. Br J Surg 1995;82:757-61.  Back to cited text no. 12
    
13.
Jacob AG, Driscoll DJ, Shaughnessy WJ, Stanson AW, Clay RP, Gloviczki P. Klippel-Trénaunay syndrome: Spectrum and management. Mayo Clin Proc 1998;73:28-36.  Back to cited text no. 13
    
14.
Peng HH, Wang TH, Chao AS, Chang YL, Shieh SC, Chang SD. Klippel-Trenaunay-Weber syndrome involving fetal thigh: Prenatal presentations and outcomes. Prenat Diagn 2006;26:825-30.  Back to cited text no. 14
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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