CLOVES Syndrome

C ongenital
L ipomatous
O overgrowth
V ascular Malformation
E pidermal nevi
S coliosis, Skeletal, Spinal anomalies

 

CLOVES Syndrome is a recently described syndrome associated with complex vascular anomalies of the central nervous system, generalized seizures, fatty overgrowth and vascular malformations.

CLOVESwas first described in the medial literature in 2007 (Sappp JC, et. al. )The patients in this study had been previously diagnosed with Proteus Syndrome but did not meet the diagnostic criteria for the disease and whose natural history was different from Proteus.

CLOVESPatients present with complex and mixed truncal vascular malformations, over growth of fat tissue, scoliosis and enlarged boney structures without progressive bony overgrowth, most often in the lower extremities and feet.  (Alomari,  2009 et al)  CLOVES syndrome is a rare disorder with a varied presentation.  Symptoms and presentation ranges from mild to severe.  At this time there is no consensus for the diagnosis of CLOVES and the manifestation of the syndrome are evolving as clinicians and scientists increase research of the disease.

***May 31, 2012- Researchers at Boston Children’s Hospital identify a genetic casue for CLOVES.  The discovery opens the doors to targeted therapeutic development and to understanding other, similar disorders.

(Full Text of Release)

Presentation of the Disease: 

Fatty Tissue Overgrowth:  (Congenital Lipomatous):  a sofft fatty mass of variable size is often seen at birth.  The mass can be seen in one or both sides of the back and abdominal wall.  The mass extends into pelvis, (groin and gluteal)  The cutaneous manifestation of the mass presents with a capillary malformation (red/pink nevi)  The fatty mass may extend into the chest, spinal cord or abdomen.

 

Vascular Anomalies:patients have abnormal lymphatic and venous channels.  Some patients have presented with arteriovenous malformations (AVM) in the area of the spinal cord.    Cutaneous (skin) anomalies include prominent veins, lymphatic channels, capillary malformations, epidermal nevi on the chest, face and neck.

Scoliosis/skeletal/Spinal Anomalies:  Abnormalities to the lower extremities and curvature of the spine is seen.  Patients present with large and wide feet and hands.  Fingers and toes are large with wide space between digits.  Often uneven size of the extremities is noted.

 

Other findings may include small or absent kidney, abnormal knee (patella), and joint abnormality- knee and hip

 

At the April 2010 International meeting of ISSVAtwo presentations on the manifestation and managment of Cloves were presented.

Physicians from the Children’s Hospital of Boston performed a retrospective study of 18 patients with distinct characteristics of CLOVES.  The study found variable portions of the truncal masses in patients were composed of lymphatic malformation.   Cpaillary malformations and high flow lesions were common.  The lipomatous mass infiltrated the adjacent anatomic spaces and was associated with capillary lymphatic, venous and arteriovenous malforamtions.  Acral deformaties include wide feet and hands, macrodactyly amd a wide “sandal gap” of the toes.  Scoliosis and other musculoskeletal, neurologic, renal and cutaneous malformations were also encountered.  This condition can be deforming and disabling; hence prompt diagnosis and care in a multidisciplinary center is necessary.

 

The management of CLOVES in a multidisciplinary setting is suggested because of the implications of the progression of this disease.  The Brussels Vascular Anomaly group presented information on their management guidelines for CLOVES in a multidisciplinary setting.

1. 1. Measure Bilogical: d-dimer levels (normal range <500mg/ml) treat accordingly with LMWH

2. Interventional Radiology- embolization and scelerotherapy

3.Plastic surgery- liposuction, surgical resection of large mass, laser

4. Orthopedic surgery- amputation for symmetry, osteotomy

 

Additionally Dr. Matt Warman, MD Orthopedic Research Lab, Children’s Hospital Boston has proposed a hypothesis as to the cause of Cloves.  His theory states that Cloves is caused by a DNA change that is unique to the individual and is only present in the individual’s affected tissue.  His research strategy is to sequence RNA and DNA from surgically excised lipomas, sequence the DNA from surgically excised lymphatic or other complex malformations from which “affected” cells hae been captured by laser or micro-dissection.  he will compare changes across patients and between patients and parents.  Dr. Warman acknowledges that there are some uniqe challenges to his research. Not every cell in the body is affected, not every cell in an affected tissue is affected, a wile allele may also be present and sequencing technology is imperfect all of these present challenges in finding causative mutations in CLOVES.  For more information on this study please contact Dr. Warman directly at 617-919-2371 or matthew.warman@childrens.harvard.edu

 

CLOVES presentation is varied, not every patient has all of these abnormalities.  The management of CLOVES is challenging and requires an multidisciplinary team of physicians with experience in overgrowth disorders and vascular anomalies.  For More information on CLOVES please contact NOVA.  We can help you find a Vascular Anomaly Center involved in the diagnosis and treatment.

References

Clin Dysmorphol. 2009 Jan;18(1):1-7.  Characterization of a distinct syndrome that associates complex truncal overgrowth, vascular, and acral anomalies: a descriptive study of 18 cases of CLOVES syndrome.

Alomari AI.  Division of Vascular and International Radiology, Department of Radiology, Children’s Hospital Boston and Harvard Medical School, Boston, Massachusetts 02115, USA. ahmad.alomari@childrens.harvard.edu

Am J Med Genet A. 2007 Dec 15;143A(24):2944-58.  Newly delineated syndrome of congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE syndrome) in seven patients.  Sapp JC, Turner JT, van de Kamp JM, van Dijk FS, Lowry RB, Biesecker LG.

Alomari AL, Comments on the diagnosis and mangement of Cloves Syndrome, 2011 Mar-Apr, 28(2):215-216

 

 

Revised 5/31/2012

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