Paradoxical association of extensive nevus flammeus together with unilateral lower limb and breast hypoplasia^†

To the Editor:

Vascular malformations may occur in association with generalized or regional overgrowth, as exemplified in Sturge–Weber and Klippel–Trenaunay syndromes [Cohen, 2006]. Here, we report an adult patient with paradoxical association of extensive nevus flammeus and unilateral lower limb and breast hypoplasia.

The proband was a 45-year-old Caucasian male. Both parents were healthy and non-consanguineous. Family history was unremarkable for cutaneous and orthopedic problems. Pregnancy and delivery were uneventful. Since birth, he presented a purple–red discoloration involving the sacral region and extending over the upper third of the buttocks and both thighs. This lesion was more evident on the right side and significantly improved with age, becoming pink–red. The same cutaneous anomaly affected the right upper limb. Psychomotor development was normal. Leg asymmetry was first noted during infancy and prompt shoe-lift application limited the development of gait problems and abnormal spine curvature. He also had congenital strabismus. On physical examination, a pink–red skin lesion was evident over the sacral region and was intermingled with areas of pale skin (Fig. 1A). Diascopic pressure demonstrated the vascular origin of these findings (i.e., nevus vascularis mixtus). A marble-like, pink–red discoloration was noted on the median aspect of both thighs, although it was more evident on the right side. The same irregular vascular lesion also involved the right upper limb. The breast was slightly hypoplastic on the ipsilateral side (Fig. 1B). The right lower limb was smaller than the left with a 4 cm length and 1.5 cm calf circumference discrepancy (Fig. 1C). Also, the right foot was 2 cm shorter than the left and with brachydactyly mainly involving the central rays together with mild 2-3 syndactyly of the toes (Fig. 1D). Radiographs confirmed these findings and demonstrated distal symphalangism of both fifth toes (Fig. 1E). Sensation, power, and tendon reflexes were normal in both legs. Pectoral, gluteal, and thigh muscles were symmetrically developed. Right external ophthalmoplegia was noted without any facial nerve paralysis. Deglutition was normal. A radiograph of the spine disclosed only mild scoliosis. Vascular ultrasound of the lower limbs demonstrated dilatation of the great saphenous vein and varicosities of the collateral vessels on the right side, but was unremarkable on the left. Doppler study showed normal blood flow.

Our patient represents an unusual combination of congenital anomalies with predominantly unilateral involvement. Extensive vascular birthmarks often accompany overgrowth in several human malformation syndromes [Cohen, 2006]. Conversely, the paradoxical association of vascular malformations and tissue hypoplasia can be occasionally observed in some hamartomatous conditions, including cutis marmorata telangiectatica congenita and phakomatosis pigmentovascularis [Garzon and Schweiger, 2004; Castori et al., 2008]. More interestingly, the appellation of “inverse Klippel–Trenaunay syndrome” has been used to define the extremely rare combination of extensive nevus flammeus spatially related to limb hypoplasia [Danarti et al., 2007]. However, the phenotype observed in our patient does not fit well with any of these conditions. In the present case, unilateral lower limb deficiency and central toe brachydactyly is somewhat reminiscent of the lower extremity counterpart of the Poland sequence, which is considered a vascular disruption sequence [Riccardi, 1978; Moeschler et al., 1989; Corona-Rivera et al., 1997; Silengo et al., 1999]. Of note, the concurrence of unilateral breast hypoplasia and, possibly, homolateral ophthalmoplegia would still be consistent with this hypothesis. Taken together, these observations suggest that a causal relationship between large vascular malformations and neighboring tissue hypoplasia may exist and that this association could be more common that expected.