CLOVES Syndrome Community

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CLOVES Syndrome stands for Congenital, Lipomatous, Overgrowth, Vascular Malformations, Epidermal Nevi and Spinal/Skeletal Anomalies and/or Scoliosis. CLOVES is caused by a somatic genetic mutation in a gene called PIK3CA that increases the activity of the gene. CLOVES belongs to a category of diseases known as PIK3CA-related overgrowth spectrum or PROS.

Last updated 04/30/2026

Clinical

Disease Class

Developmental anomalies during embryogenesis

Genetic diseases

Vascular disease

Body Systems

Cardiovascular / Circulatory

Digestive

Endocrine

Hematopoietic / Lymphatic / Immune

Metabolic

Muscular / Skeletal

Nervous / Sensory

Renal / Urinary / Excretory

Reproductive

Respiratory

Organs

Arteries

Blood

Blood vessels (veins, arteries)

Bones

Brain

Connective tissue / joints

Ears

Esophagus

Heart

Intestines

Kidneys

Liver

Lungs

Lymph fluid, nodes, ducts, vessels

Mouth / teeth

Muscles

Nose

Pancreas

Scrotum

Skin

Spinal cord

Stomach

Throat/pharynx

Veins

Known Genetic Link

Yes, one or more genes directly cause the condition

Causative Genes

PIK3CA

Contributory Genes

None specified / unknown

Type of Inheritance

De novo

Newborn Screening

Disease Mechanism(s)

Abnormal cell proliferation

Vascular/Angiogenesis Defects

Age of Onset

Infancy (age 0-1)

Prebirth

Average Age at Diagnosis

Early childhood (age 1+-5)

Infancy (age 0-1)

Life Expectancy

Adulthood (age 18-64)

Affected Sex(es)

Female

Intersex

Male

National Prevalence

101-1000

Global Prevalence

1001-10000

National Incidence

Unknown

Global Incidence

Unknown

Symptoms / Phenotypes

asymmetric body parts

capillary malformation

cranial hyperostosis

infection, unspecified location

lipoma

lymphatic malformations

macrodactyly

muscle weakness

overgrowth of extremities

paralysis

pulmonary embolism

renal hypoplasia/aplasia

sandal gap

seizures / epilepsy

spinal dysraphism

tethered cord

venous malformation

Biomarkers

Diagnostic

· Somatic PIK3CA mutation from tissue from overgrown areas of body

Therapeutic

· Lymphatic malformation size vs. baseline; fatigue vs. baseline; pain vs. baseline

Existing Therapies

Expanded access (Compassionate Use)

Off-Label Drug Use

Regulatory Agency-Approved to Cure or Modify the Disease

· Alpelisib/Vijoice

Therapies in Development

Repurposed drug

· 4 - Alpelisib/Vijoice (approved, researched)

Therapeutic Development Stages

Approved/Available

In clinical trials (Phase I, II, III, or IV)

In research/exploratory phase

Therapeutic Development Role

Focus group participation or coordination

Outcome measures development

Recruitment and outreach to patients

Study protocol design and/or review (includes selection of outcome measures)

Organizational & Research

Cell Lines

Fibroblasts

iPSCs

Cell Lines, Institution

CRUK Scotland Institute

University of Edinburgh

Cell Lines, Involvement

Consulted

Funded

Cell Lines, share

Unsure

Disease Model

Mouse

Zebrafish

Disease Model, Involvement

Consulted

Funded

Disease Model, share

Unsure

Organizational Challenges

None

Clinical Trial Role

Outcome measures, development

Recruitment and outreach, patients

Study protocol design, review

Clinical Trial Types

Phase 1

Phase 2

Biobank, Institution

None

Center of Excellence, Institution

None

Registry

Yes, we have a registry that we created

Data Collected, Registry

Clinical data

Genetic data

Imaging data

Longitudinal natural history data

Medication usage

Patient contact info

Patient-reported data

Data Entered by, Registry

Patients

Platform, Registry

IAMRARE

Natural History Study

Yes, we have a natural history study that we created

Data Collected, Natural History Study

Genetic data

Imaging data

Medication usage

Patient-reported outcomes

Retrospective data

Platform, Natural History Study

IAMRARE

FDA Patient Listening Session

FDA Patient-Focused Drug Development (PFDD) Program

ICD Codes

We use an ICD-10 code capturing the family of diseases to which our disease belongs

We use an ICD-11 code capturing the family of diseases to which our disease belongs

Diagnostic Guidelines

Yes, we have guidance available on our website

Yes, we have accredited guidelines

Science Advisory Board Policies

Yes, willing to share SAB policies

Research Network Policies

Has CRN but no policies

Patient Priority Survey

IDK

Research Roadmap

Yes we have a Research Roadmap, and will share policies

None

Europe

North America

Europe