The syndromes listed below have similar and/or overlapping symptoms with CLOVES Syndrome. Klippel-Trenaunay syndrome (KTS), Proteus Syndrome and Macrocephaly-Capillary Malformation all encompass overgrowth and vascular anomalies. The information below describes each syndrome, and highlights the differences between CLOVES and these other syndromes.
KLIPPEL-TRENAUNAY SYNDROME (KTS)
KTS often has three characteristic signs:
1 -Capillary malformation covering one or more limbs (arm or leg)
2 - Overgrowth — or excessive growth — of a limb (usually a leg)
3 -Abnormal blood vessels, including veins, capillaries and lymphatic vessels
Some of the medical challenges associated with KTS are: blood clots, cellulitis (infections in the skin), anemia (due to blood loss because of easy bleeding), severe pain and heaviness of the affected limb and size differences in the limbs.
Doctors can sometimes see evidence of KTS in a prenatal ultrasound and the capillary malformation (sometimes called a port wine stain) is almost always apparent when a child with KTS is born.
Proteus syndrome (PS) is a rare, complex disorder that involves overgrowth of body parts along with vascular anomalies, areas of bone overgrowth, epidermal nevi, connective tissue nevi and other connective tissue components. Some patients may have fatty tumors called lipomas or atrophy on some parts of their bodies. This is a rare, progressive condition where children are usually born without any obvious differences, and acquire them over time. This distinguishes PS from many other overgrowth syndromes including CLOVES, M-CM and KTS.
There are three general characteristics or features that must be present for doctors to consider a diagnosis of Proteus syndrome:
1 - Mosaic distribution: this means that the areas of overgrowth are patchy and that only some body parts show signs of overgrowth while others are unaffected
2 - Sporadic occurrence: this means that no one else in the affected person’s family has similar features of overgrowth
3 - Progressive course: this means that the overgrowth has noticeably altered the appearance of the affected body parts over time or that new areas of overgrowth have appeared over time
If a person has all three of these general characteristics in addition to some specific characteristics, doctors may consider a diagnosis of Proteus syndrome.
Proteus syndrome can affect any part of the body but commonly affects the bones and skin. Overgrowth of a bone can cause orthopedic problems, and overgrowth of the skin can cause cosmetic and other concerns. Less commonly, individuals with Proteus syndrome have lung problems that require monitoring. Many children and adults with Proteus syndrome have normal intelligence and have good general health. Children and adults with Proteus syndrome are at risk to get a type of blood clot called a “DVT,” or deep vein thrombosis, which can cause a serious problem called a pulmonary embolism. It is important for doctors caring for people with Proteus syndrome to be aware of this risk.
MACROCEPHALY – CAPILLARY MALFORMATION (M-CM)
Macrocephaly-capillary malformation (M-CM) is a multiple malformation syndrome causing abnormal body and head overgrowth and abnormalities of the skin, vascular system, brain and limbs. The disorder is assumed to have a genetic basis, but the exact cause is unknown. A diagnosis of M-CM is currently made based solely on clinical observations. Though not every affected individual has all features, commonly found signs include macrocephaly, congenital macrosomia, extensive cutaneous capillary malformations, body asymmetry, extra or fused fingers or toes, lax joints, doughy skin, variable developmental delays and other neurologic problems such as seizures and low muscle tone.
M-CM was first described in the medical literature in 1997. At that time it was named macrocephaly-cutis marmorata telangiectatica congenita syndrome (M-CMTC) and this term is occasionally still used.