overgrowth syndrome
Overgrowth syndromes in children constitute a group of rare disorders that are characterised by tissue hypertrophy. Individual overgrowth syndromes have been shown to overlap with regard to clinical and radiologic features. The details of the gene ...
with complex vascular anomalies. CLOVES syndrome affects people with various symptoms, ranging from mild fatty soft-tissue tumors to vascular malformations encompassing the spine or internal organs.
It is a genetic disorder that results from somatic, mosaic gain-of-function mutations of the ''PIK3CA'' gene, and belongs to the spectrum of ''PIK3CA''-related overgrowth syndromes (PROS). This rare condition has no specific treatment and a poor survival rate.
French doctor Guillaume Canaud published an article i Nature that demonstrate the efficacy of BYL719 (From cancer), an inhibitor of PIK3CA, in preventing and improving organ dysfunction. It seems this treatment is having tremendous and quick effects.
CLOVES syndrome is closely linked to other overgrowth disorders like
proteus syndrome
Proteus syndrome is a rare disorder with a genetic background that can cause tissue overgrowth involving all three embryonic lineages. Patients with Proteus syndrome tend to have an increased risk of embryonic tumor development.Freedberg, et al. ...
,
Klippel–Trénaunay syndrome
Klippel–Trénaunay syndrome, formerly Klippel–Trénaunay–Weber syndrome and sometimes angioosteohypertrophy syndrome and hemangiectatic hypertrophy, is a rare congenital medical condition in which blood vessels and/or lymph vessels fail to ...
,
Sturge–Weber syndrome
Sturge–Weber syndrome, sometimes referred to as encephalotrigeminal angiomatosis, is a rare congenital neurological and skin disorder. It is one of the phakomatoses and is often associated with port-wine stains of the face, glaucoma, seizures, i ...
, and
hemihypertrophy
Hemihypertrophy, now more commonly referred to as hemihyperplasia in the medical literature, is a condition in which one side of the body or a part of one side of the body is larger than the other to an extent considered greater than the normal v ...
, to name a few.
'CLOVES' is an acronym for:
* C is for
congenital
A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...
.
* L is for
lipoma
A lipoma is a benign tumor made of fat tissue. They are generally soft to the touch, movable, and painless. They usually occur just under the skin, but occasionally may be deeper. Most are less than in size. Common locations include upper back, ...
tous, which means pertaining to or resembling a benign tumor made up of mature fat cells. Most CLOVES patients present with a soft fatty mass at birth, often visible on one or both sides of the back, legs and/or abdomen.
* O is for overgrowth, because there is an abnormal increase in the size of the body or a body part that is often noted at birth. Patients with CLOVES may have affected areas of their bodies that grow faster than in other people. Overgrowth of extremities (usually arms or legs) is seen, with large wide hands or feet, large fingers or toes, wide space between fingers, and asymmetry of body parts.
* V is for
vascular malformation
A vascular malformation is a blood vessel or lymph vessel abnormality. Vascular malformations are one of the classifications of vascular anomalies, the other grouping is vascular tumors. They may cause aesthetic problems as they have a growth cycl ...
s, which are blood vessel abnormalities. Patients with CLOVES have different venous, capillary, and lymphatic channels - typically capillary, venous and lymphatic malformations are known as "slow flow" lesions. Some patients with CLOVES have combined lesions (which are fast flow) and some have aggressive vascular malformation known as
arteriovenous malformation
Arteriovenous malformation is an abnormal connection between arteries and veins, bypassing the capillary system. This vascular anomaly is widely known because of its occurrence in the central nervous system (usually cerebral AVM), but can appea ...
s (AVM). The effect of a vascular malformation varies per patient based on the type, size, and location of the malformation, and symptoms can vary.
* E is for Epidermal
naevi
Nevus (plural nevi) is a nonspecific medical term for a visible, circumscribed, chronic lesion of the skin or mucosa. The term originates from ''nævus'', which is Latin for "birthmark"; however, a nevus can be either congenital (present at bir ...
, which are sharply-circumscribed chronic lesions of the skin, and benign. These are often flesh-colored, raised or warty.
* S is for Spinal/Skeletal Anomalies or
scoliosis
Scoliosis is a condition in which a person's spine has a sideways curve. The curve is usually "S"- or "C"-shaped over three dimensions. In some, the degree of curve is stable, while in others, it increases over time. Mild scoliosis does not t ...
. Some patients with CLOVES have
tethered spinal cord
Tethered cord syndrome (TCS) refers to a group of neurological disorders that relate to malformations of the spinal cord. In this initial description the syndrome is named CLOVE syndrome. It is believed that the first description of a case of CLOVES syndrome was written by Hermann Friedberg, a German physician, in 1867.
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Causes
Somatic mutation
A somatic mutation is a change in the DNA sequence of a somatic cell of a multicellular organism with dedicated reproductive cells; that is, any mutation that occurs in a cell other than a gamete, germ cell, or gametocyte. Unlike germline mutatio ...
s in the PIK3CA have been identified as a cause of CLOVES syndrome. PIK3CA is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
involved in the PI3K-AKT signalling pathway. Mutations in other parts of this pathway cause other overgrowth syndromes including
Proteus syndrome
Proteus syndrome is a rare disorder with a genetic background that can cause tissue overgrowth involving all three embryonic lineages. Patients with Proteus syndrome tend to have an increased risk of embryonic tumor development.Freedberg, et al. ...