CLOVES syndrome

CLOVES Syndrome: A Rare Congenital Disorder

CLOVES syndrome, also known as Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevi, and Skeletal Anomalies, is a rare congenital disorder characterized by abnormalities in multiple organ systems.

• Vascular Abnormalities: CLOVES syndrome involves malformations of the vascular system, which can lead to problems with blood flow and circulation.
• Skin Abnormalities: The condition also causes skin overgrowth, known as epidermal nevi, which can be disfiguring and painful.
• Spinal and Skeletal Abnormalities: CLOVES syndrome is associated with abnormalities in the spine, joints, and bones, including scoliosis and hip dysplasia.
• Musculoskeletal Problems: Affected individuals may also experience muscle weakness or spasticity.

Causes and Prevalence

CLOVES syndrome is a rare genetic disorder, with only a few reported cases worldwide. The exact cause of the condition is unknown, but it is believed to be related to mutations in specific genes involved in embryonic development.

Symptoms and Diagnosis

The symptoms of CLOVES syndrome can vary widely from person to person, but may include:

• Congenital overgrowth of fatty tissue
• Vascular malformations
• Epidermal nevi (skin overgrowths)
• Skeletal anomalies (abnormalities in the spine, joints, and bones)

Diagnosis is typically made through a combination of clinical evaluation, imaging studies (such as MRI or CT scans), and genetic testing.

References

1. CLOVES syndrome is characterized by Congenital Lipomatous Overgrowth, Vascular malformations, Epidermal nevi, and Skeletal anomalies [1].
2. The condition involves abnormalities in blood vessels, skin, spine, joints, and bones [3].
3. Affected individuals may also experience muscle weakness or spasticity [9].

CLOVES Syndrome Signs & Symptoms

CLOVES syndrome, also known as Congenital Lipomatous Overgrowth with Vascular Malformations and Epidermal Nevi and Scoliosis/Skeletal/Spinal Anomalies, is a rare genetic disorder characterized by several distinct signs and symptoms.

• Fatty tissue masses: Soft lumps, also called lipomas, that form under the skin are often found on the stomach, back, or sides of individuals with CLOVES syndrome [1][4].
• Problems with feet and hands: Large, wide hands and feet are common in children with CLOVES syndrome [1][8].
• Disproportionate fat distribution: Individuals with CLOVES syndrome may experience uneven fat distribution, leading to soft lumps or fatty tissue masses on various parts of the body [3].
• Overgrowth of extremities: The arms and legs may grow disproportionately large in children with CLOVES syndrome [3].
• Skin abnormalities: Epidermal nevi, which are benign growths on the skin, can be present in individuals with CLOVES syndrome [2][5].
• Kidney problems: Some individuals with CLOVES syndrome may experience kidney-related issues [3].

It's essential to note that each child with CLOVES syndrome may exhibit a unique combination of these signs and symptoms. If you suspect your child has CLOVES syndrome, consult a qualified healthcare professional for an accurate diagnosis and guidance.

References: [1] What Are the Signs & Symptoms of CLOVES Syndrome? · fatty tissue masses on the belly, back, or sides · problems with feet and hands (large, wide hands and feet; ... [2] Aug 5, 2020 — CLOVES stands for congenital lipomatous (fatty) overgrowth, vascular malformations, epidermal nevi and scoliosis/skeletal/spinal anomalies. [3] Other signs and symptoms may include disproportionate fat distribution, overgrowth of the extremities (arms and legs), skin abnormalities and kidney problems ... [4] Mar 4, 2024 — CLOVES Syndrome Symptoms · Fatty tissue overgrowth: Soft lumps—also called lipomas —that form under the skin are often found on the stomach, ... [5] C: Congenital (present at birth) · L: Lipomatous (referring to lipomas, soft fatty masses often found on one or both sides of the back and belly) · O: Overgrowth ...

Diagnostic Tests for CLOVES Syndrome

CLOVES (Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal nevi, Spinal and Skeletal anomalies) syndrome diagnosis involves a combination of clinical evaluation, imaging studies, and genetic testing.

• Clinical Evaluation: Doctors will look for the characteristic combination of vascular, skin, and spinal problems that define CLOVES syndrome. This includes examining the patient's physical features, medical history, and symptoms.
• Imaging Studies: Advanced imaging tests such as MRI, CT scan, and ultrasound may be used to confirm the presence of vascular malformations, epidermal nevi, and other characteristic features of CLOVES syndrome.
• Genetic Testing: A diagnosis of CLOVES syndrome is confirmed by identifying a mosaic PIK3CA variation on affected tissue without culture, using high-depth high-throughput sequencing [5]. This genetic test helps to rule out other conditions that may present with similar symptoms.

Key Diagnostic Tests

• Sonographic screening for Wilms tumor in children with CLOVES syndrome [6]
• High-depth high-throughput sequencing for PIK3CA variation [5]

Important Considerations

• Diagnosis of CLOVES syndrome is usually made at birth based on a baby's physical problems and advanced imaging tests [8].
• Experienced vascular anomaly specialists are essential for managing or preventing symptoms with the right medical and surgical care [1].

References:

[1] Context 1 [5] Context 5 [6] Context 6 [8] Context 8

Treatment Options for CLOVES Syndrome

CLOVES (Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal nevi, Scoliosis/Spinal deformities, and Skeletal abnormalities) syndrome is a rare congenital disorder that requires an interdisciplinary approach to treatment. While there is no cure for CLOVES syndrome, various drug treatments have shown promise in managing its symptoms.

Sirolimus (Rapamycin)

• Sirolimus, also known as rapamycin, has emerged as an alternative treatment for CLOVES syndrome [4][6].
• Its use in PROS disorders has demonstrated that it can reduce the size of vascular abnormalities and improve quality of life [4][6].

Alpelisib

• Alpelisib, a PI3K inhibitor, has been approved for the treatment of advanced or metastatic breast cancer [7].
• Uncontrolled single and multiple case reports have shown some reduction in size of vascular abnormalities and improvement in quality of life when using alpelisib to treat CLOVES syndrome [11].

Other Treatment Options

• Surgery and other medical interventions are often used to manage the symptoms of CLOVES syndrome, such as overgrowth, vascular anomalies, and related medical issues [12].
• Researchers are exploring new targeted treatment medications to treat CLOVES/PROS, offering hope for improved patient care [12].

Important Considerations

• Early detection and treatment are crucial in managing CLOVES syndrome [1].
• Children with CLOVES syndrome should be considered for quarterly abdominal ultrasonography until age 7 years to monitor the disease progression [10].

It is essential to consult with a healthcare professional to discuss the best course of treatment for an individual with CLOVES syndrome.

References:

[1] Context result 1 [4] Context result 6 [6] Context result 6 [7] Context result 7 [11] Context result 11 [12] Context result 12

The differential diagnosis for CLOVES (Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevi, Scoliosis/Skeletal and Spinal anomalies) syndrome is a crucial aspect of its clinical evaluation. Based on the search results, here are the key points to consider:

• Proteus Syndrome: This is the most common differential diagnosis for CLOVES syndrome, with many patients being misdiagnosed as having Proteus syndrome in the past [1][4]. The presentations in CLOVES syndrome and Proteus syndrome are strikingly similar, making it essential to differentiate between the two conditions.
• KTS (Klippel-Trenaunay-Weber) Syndrome: KTS is another condition that should be considered in the differential diagnosis of CLOVES syndrome [6][14]. It is characterized by vascular malformations, limb hypertrophy, and epidermal nevi.
• Other PROS Disorders: The PIK3CA-related overgrowth spectrum (PROS) disorders are a group of conditions that share similar clinical features with CLOVES syndrome. These include other rare syndromes such as KTS and others [1][7].
• Genetic Testing: Genetic testing may aid in confirming the diagnosis, particularly in cases where there is suspicion of mosaic mutations in the PIK3CA gene [7].

It's essential to note that the differential diagnosis for CLOVES syndrome requires a comprehensive clinical evaluation, including cutaneous, vascular, truncal, spinal, and limb anomalies. A thorough medical history and physical examination are crucial in differentiating CLOVES syndrome from other conditions.

References:

[1] Biesecker LG. PIK3CA-related overgrowth spectrum (PROS): diagnostic and testing eligibility criteria, differential diagnosis, and evaluation. Am J Med Genet A. 2015 Feb;167A(2):287-95. [4] The most important differential diagnostic considerations embrace Proteus syndrome, KTS and other PROS disorders (Box 1). [6] by EÖ Durmaz · 2022 · Cited by 6 — Differential Diagnosis. The most important differential diagnosis is Proteus syndrome. [7] Parker VER, et al. PIK3CA -related overgrowth spectrum (PROS): Diagnostic and testing eligibility criteria, differential diagnosis, and evaluation. Am J Med Genet A. 2015;167(2):287-295. doi:10.1002