A 32-year-old woman was referred after her second-trimester ultrasound examination demonstrated that the fetus had two abnormal feet. First-trimester screening had identified the pregnancy as high risk (1 in 134 chance) for trisomy 21. Amniocentesis had been declined by the patient at this time.
The initial tertiary examination at 24 + 2 weeks' gestation demonstrated a male fetus with marked edema of the lower limbs, with the right leg being worse than the left (Figure 1). Large pockets of fluid/cystic spaces were evident in the lower limbs, pelvis and inferior retroperitoneum. Differential diagnoses of chromosomal (trisomy 21 or 18) or genetic syndromes or structural abnormalities such as lymphangioma were considered. An amniocentesis was performed, showing a karyotype of 46,XY. Counseling with the obstetric/pediatric surgical team considered a range of possible outcomes including significant disability. The parents decided to continue with the pregnancy.
Ultrasound examinations were performed at 26 + 2, 28 + 2 and 30 + 2 weeks' gestation. Over these examinations there was minimal change to the edema and the cystic spaces did not change or show vascularity. However, the feet deformities became more apparent. The right foot was markedly hypertrophied with fusion of the second and third toes (Figure 2). The left side appeared less affected. It was not possible to make a definitive diagnosis, but the most likely diagnosis appeared to be Klippel–Trénaunay syndrome (KTS). Magnetic resonance imaging (MRI) was performed at 32 weeks, confirming the features observed on ultrasound examination.
An ultrasound examination at 32 + 2 weeks included a targeted examination of the lower-limb vascular system. The external iliac veins were present, and the great saphenous vein could be demonstrated on the left side (Figures 1a and b). The femoral/popliteal veins could not be demonstrated in either limb (Figures 1b and c), however, the position of the fetus limited evaluation of the right superficial venous system. The lateral thigh area was examined on both sides for congenital embryonal veins but these were not seen. The major arteries were present. Hypoplasia/aplasia of the deep venous system was suspected, making a diagnosis of KTS much more likely.
Elective Cesarean section was performed at 38 + 3 weeks' gestation and postnatal clinical examination confirmed the ultrasound findings. In addition, there were marked bilateral dark purple superficial capillary malformations occupying much of the skin below the waist. Extensive subcutaneous and deep cystic changes correlating with some of these areas were observed on postnatal MRI and ultrasound examination. The buttocks, scrotum, both legs and feet were all affected. The right foot had hemihypertrophy and syndactyly. Left hallux hypertrophy was seen (Figure 3).
Postnatal ultrasound examination of the lower limbs (at 7 months) demonstrated normal external iliac veins, common femoral and profunda femoral veins. The saphenofemoral junctions were dilated bilaterally. The right femoral vein below the profunda femoral vein and the superior two-thirds of the popliteal vein were absent. The left femoral vein below the profunda femoral vein was also absent. The left popliteal vein could not be imaged owing to the infant's being distressed. In addition, the lateral thigh contained large persistent embryonal veins.
Consultation with geneticists and the vascular malformation clinic placed the infant in the spectrum of KTS, confirming the prenatal diagnosis.
KTS, first described in 19001, is a rare congenital abnormality traditionally distinguished by a triad of clinical characteristics. These are capillary vascular malformation, abnormal venous formation and osseous/soft-tissue hypertrophy2; a diagnosis has typically been established if a person has two out of three of these features3. Difficulty arises in diagnosis as there is some overlap in the published diagnostic criteria with other syndromes such as Parkes Weber and Proteus syndromes4. This can be a source of confusion, and led Oduber et al.4 to propose a detailed classification system based on two major groups of anomalies. The first grouping is ‘congenital vascular’ malformations, which include capillary vascular malformations and venous abnormalities. The second group relates to changes in limb size (‘disturbed growth’). There are other non-essential findings that are recognized as being related to this diagnosis, and each major group has subgroups. Diagnosis relies on there being a feature from each of the major groups (Table 1)4.
Table 1. Classification of Klippel–Trénaunay syndrome
Group A, congenital vascular malformations
Group B, disturbed growth (can include hyperplasia or hypoplasia)
Other features non-essential for the diagnosis
Diagnosis requires features from both Groups A and B. Adapted from Oduber et al.4.
Even with this refined classification, definitive diagnosis of KTS is problematic. There remains significant overlap among the uncommon syndromes that have a combination of vascular malformation and growth disturbance. Limb hypertrophy is the most variable feature of KTS, presenting as edema, limb-length variation and some dysmorphism3. Digit anomalies are common, such as the syndactyly that was evident in this case. Observation of these features, while important, is non-specific, and prenatal diagnosis may depend on establishing and classifying the vascular anomaly, but this is problematic because of an inability to adequately observe superficial vascular malformations. Hence providing as much detail as possible about a vascular malformation will be important in classifying the abnormality.
Limb hypertrophy can be associated with angiomatosis such as hemangiomas and lymphangiomas or other phakomatoses such as Parkes Weber syndrome5, but the distinctive feature of KTS is its vascular anomalies6. Atypical venous anatomy occurs commonly in this setting (72%)3. The variants commonly seen in adults are deep and superficial varicosities and the presence of the persistent embryonic lateral marginal vein3. Hypoplasia or aplasia of the venous system, as in this case, is less commonly seen but is a recognized part of the KTS spectrum3. These anatomical variants mostly present in the femoral and popliteal veins3. Until this case, none of these changes had been reported prenatally.
Peng et al.7 reviewed 19 cases of pre- and perinatal diagnosis of KTS involving the thigh reported in the literature before 2006. Adding two of their own cases, they report the key features of these cases. Prenatal ultrasonography was able to demonstrate abdominal, pelvis and thigh cystic masses as evident in our case. Other findings included polyhydramnios, cardiomegaly, thick placenta, non-immune hydrops fetalis and oligohydramnios. In this review and a subsequent prenatal description of KTS8, there are no reports that we are aware of in which a detailed venous anatomical variant has been documented. In this case, the femoral and popliteal vein hypoplasia seen prenatally was distinctive of KTS.
Examination of the lower limb venous system is rarely of value in prenatal ultrasound though it may be considered if a vascular anomaly is suspected. This case suggests that sonographic evaluation of the lower leg deep and superficial venous systems may be of significant value in establishing a prenatal diagnosis of KTS.