Case of the Week
Section Editors: Matylda Machnowska1 and Anvita Pauranik2
1University of Toronto, Toronto, Ontario, Canada
2BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
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October 3, 2024
Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevi, and Skeletal Anomalies (CLOVES) Syndrome
- Background:
- CLOVES syndrome is a recently described, rare overgrowth syndrome characterized by congenital lipomatous overgrowth (CLO), vascular malformations (V), epidermal nevi (E), and skeletal (S) abnormalities. The syndrome is grouped under the PIK3CA-related overgrowth spectrum (PROS), which is attributed to postzygotic activation of the PIK3CA gene, impacting the Akt-mTOR signaling pathway that leads to cell proliferation.
- Clinical presentation:
- With fewer than 150 cases reported globally as of 2016, CLOVES syndrome presents at birth with asymmetric lipomatous overgrowth, vascular malformations, skeletal anomalies, and epidermal nevi.
- Key diagnostic features:
- Lipomatous overgrowth: Patients may exhibit variable degrees of lipomatous overgrowth, which typically affects the trunk but may be seen in the extremities. On MR imaging, lipomatous masses demonstrate high T1 signal with drop-out on fat-saturated images.
- Vascular anomalies: Both low-flow vascular malformations (lymphatic, venous, capillary) and high-flow (arteriovenous) vascular malformations are seen in the syndrome, demonstrating high T2 and STIR signal on MRI.
- Musculoskeletal anomalies: Skeletal anomalies are common presentations in individuals with CLOVES syndrome and may include scoliosis, vertebral anomalies, and rib anomalies. Acral deformities include large, wide feet and hands, macrodactyly, and a wide sandal gap.
- Genetic testing may aid in confirming the diagnosis, particularly in cases where there is suspicion of mosaic mutations in the PIK3CA gene.
- Differential diagnosis:
- Proteus syndrome: Characterized by cerebriform connective tissue nevi and overgrowth of various tissues, including skin, bones, and other organs. However, it typically lacks the distinct vascular malformations seen in CLOVES syndrome.
- Klippel-Trenaunay syndrome: Presents with capillary malformations, venous varicosities, and limb hypertrophy. It may have some overlapping features with CLOVES syndrome but does not have the lipomatous truncal masses characteristically seen in CLOVES syndrome.
- Fibroadipose hyperplasia: Characterized by localized overgrowth of adipose tissue and fibrous elements, typically without the systemic involvement seen in CLOVES syndrome.
- Management:
- Management of CLOVES syndrome requires a multidisciplinary approach involving specialists from various fields, including genetics, dermatology, orthopedics, and vascular surgery. Treatment strategies include surgical and medical management. Surgical debulking of the lipomatous masses may be done when appropriate. Sirolimus, a direct inhibitor of mTOR, has shown promise in managing the symptoms associated with CLOVES syndrome, particularly the vascular malformations. Long-term monitoring and supportive care are essential to address the evolving needs of patients with CLOVES syndrome.
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