CLOVES Syndrome Awareness Day 2026: Make Access and Follow-Through Visible

CLOVES is an acronym for congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and scoliosis or other skeletal and spinal findings. The name describes a recognizable clinical pattern, while the molecular framework places CLOVES within PROS. Postzygotic activating variants in PIK3CA can be present in only a proportion of cells, which is why findings can be segmental, why phenotype varies, and why routine testing of an easily obtained sample may not answer every diagnostic question. Recent molecular series reinforce the importance of sensitive sequencing and specialist planning when low-level mosaicism is suspected.^8,14

For executives, the central problem is not simply rarity. It is the interaction of rarity with fragmentation. A person may need genetics, dermatology, hematology, vascular anomalies expertise, interventional radiology, surgery, orthopedics, neurology, pain care, rehabilitation, behavioral health, pharmacy, primary care, and social support. Those needs rarely appear in a neat order. A new symptom, planned procedure, insurance change, move, school transition, pregnancy question, or shift from pediatric to adult care can reopen the pathway. If responsibility is not explicit, the person or caregiver becomes the default integrator.

Patient-centered research documents that burden. A mixed-methods journey map found long routes to diagnosis, difficulty accessing genetic testing and qualified specialists, repeated medical events, pain, school and work disruption, financial pressure, and a particularly difficult transition to adult care.¹⁵ A separate survey of adults with complex vascular anomalies found that navigation was associated with the quality of information exchange and access to a vascular-anomaly specialist. Self-advocacy alone was not enough.⁹ This is an organizational finding: resilience is valuable, but a safe system cannot require exceptional persistence as the admission ticket to coordinated care.

A reliable pathway has four visible properties. First, it gives patients, families, and referring clinicians a plain-language entry point. Second, it names the team that accepts responsibility for triage and coordination. Third, it connects molecular, anatomic, functional, and patient-reported information before major decisions. Fourth, it keeps unresolved work visible across organizational boundaries. These are not clinical protocols. They are management controls that allow qualified professionals to apply judgment without losing the person between services.

A common failure mode in mosaic disorders is treating a negative or incomplete test as the end of inquiry. The clinical question, sample source, variant allele fraction, sequencing depth, bioinformatic threshold, and laboratory capability all influence what can be detected. In a 13-person series using targeted deep sequencing, pathogenic mosaic PIK3CA variants were identified in all participants, including six positive controls.⁸ A separate five-person series identified four somatic pathogenic variants and recommended deep sequencing rather than relying only on hotspot testing when PROS is suspected.¹⁴ These are small selected series, so they support a diagnostic principle, not a guaranteed yield.

The operational response is a genetics-informed testing plan. Before collection, the ordering team should clarify the clinical hypothesis, the tissue or fluid most likely to contain the variant, procedural opportunities that could avoid an additional invasive collection, specimen handling, assay sensitivity, consent, expected turnaround, and what the team will do with a positive, negative, or uncertain result. This requires coordination among clinical genetics, the treating specialty team, pathology or laboratory medicine, radiology, and the person or family. It should never be reduced to an instruction to obtain a biopsy.

An 82-person Chinese cohort illustrates another reason to avoid shortcuts. Sixty-seven participants carried PIK3CA variants, six had PIK3CA plus another variant, and seven people with overlapping PROS manifestations had variants in other pathway genes. The investigators described potential population-specific phenotype and genotype patterns and called for larger cohorts.⁷ The lesson is not to use ancestry as a diagnostic proxy. It is to recognize that reference populations and variant knowledge can be uneven, and that equitable precision medicine requires access to qualified interpretation.

Diagnosis is also a communication task. The record should distinguish what is confirmed, what remains suspected, which findings are clinically important now, which changes should prompt reassessment, and who can explain the result in plain language. A portable one-page summary can help primary care, emergency, school, rehabilitation, dental, surgical, and community teams understand the condition without requiring the person to reconstruct years of history at every encounter. The summary should be maintained by the clinical team, protected as health information, and updated after major changes.

People with CLOVES may undergo imaging, sclerotherapy, embolization, surgery, orthopedic procedures, dental care, or other interventions across different sites and life stages. The executive risk is not that one specialty lacks expertise. It is that relevant knowledge is distributed and arrives at different times. A procedural plan can be technically sound yet unsafe if the team has not reconciled vascular anatomy, prior complications, coagulation findings, current medicines, anesthesia considerations, positioning, skin or tissue vulnerability, mobility needs, postoperative pain, thrombosis prevention, and the recovery environment.

The literature supports caution. In the 29-patient sirolimus cohort that included CLOVES and related capillary, lymphatic, and venous malformations, the authors described high morbidity from pain, infection, bleeding, and clotting complications and reported changes across symptoms, quality of life, coagulation markers, imaging, and toxicity.¹² The MOSAIC safety study reported one grade 3 drug-related deep vein thrombosis among 49 participants.³ These findings do not define an individual's procedural risk. They show why the pathway must surface bleeding and thrombosis history, laboratory interpretation, medication exposure, and specialty ownership before a procedure.

A high-reliability huddle should occur early enough to change the plan. It should identify the procedure owner, required consultants, current imaging, the question each image must answer, the plan for medication review, blood-management or coagulation input when relevant, anesthesia and positioning needs, recovery location, pain and rehabilitation plan, and who will communicate changes to the person and family. A last-minute checklist cannot replace specialty review. The huddle is a forcing function that verifies the reviews have occurred and that their recommendations agree.

The pathway also needs a pause rule. New symptoms, infection, unexpected laboratory findings, unavailable blood products or equipment, missing imaging, uncertain medication instructions, or an unresolved specialty disagreement should trigger a named escalation route. The person and family should know whom to contact before and after the procedure, what the organization has defined as an urgent concern, and where the current plan is documented. Those instructions must come from the treating team and local policy. An observance article should never invent them.

After the intervention, close the loop. Record whether the intended functional or symptom goal changed, whether complications occurred, what follow-up is needed, and whether the next team accepted responsibility. Recovery information should reach primary care and other relevant clinicians. If tissue or fluid was obtained for an approved molecular plan, verify specimen handling and result ownership. A completed procedure is not the end of the pathway when the result, rehabilitation, monitoring, or next decision remains open.

Rare expertise is often regional, while everyday care happens locally. The operating model should connect a specialty center with primary care, local laboratories and imaging, rehabilitation, schools, emergency services, and community resources without expecting every question to trigger long-distance travel. Telehealth can reduce some burden, but only when licensing, privacy, technology, accessibility, language, reimbursement, examination limits, and local follow-through are addressed. A video visit that produces an unowned order or an impossible travel plan is not coordinated care.

The navigation survey provides a practical direction. Among 136 adults with complex vascular anomalies, most of whom reported PROS, stronger information exchange and access to a vascular-anomaly specialist were associated with better navigation. In an exploratory analysis, primary-care knowledge was also associated with navigation.⁹ The sample was predominantly women, White and non-Hispanic, and college educated, so the estimates should not be generalized without caution. Still, the study helps leaders focus on modifiable system features rather than telling people to advocate harder.

Build a hub-and-network model. The specialty hub should define which questions require in-person assessment, what can be completed locally, how images and results move, and how local clinicians can obtain timely advice. The local team should know the current plan, safety considerations, and escalation route. The navigator should identify travel, lodging, wage loss, caregiving, disability access, equipment, language, and connectivity needs early enough to change the plan. When a person misses care, the system should distinguish choice from barriers and create a safe recovery process.

Transition to adult care deserves its own workstream. The patient journey study identified transition as a particularly difficult stage.¹⁵ A transition is not complete when a pediatric clinic sends records. It is complete when an adult team with appropriate capability accepts responsibility, the medication and monitoring plan has no gap, insurance and pharmacy arrangements are active, the person understands how to seek help, and primary care knows the new roles. Readiness should be assessed over time and adapted for cognitive, communication, and guardianship needs.

Evidence equity also matters. The 82-person East Asian cohort addressed a literature base historically concentrated in Europe and North America and described potentially distinctive variant and phenotype patterns.⁷ Health systems should ask who is missing from genetic testing, specialty referral, registries, patient-reported outcome collection, trials, and long-term follow-up. Stratification can reveal access gaps, but small cell sizes in rare disease create privacy risks. Data governance should protect individuals while still allowing inequity to be recognized and corrected.

The goal is not to redesign every specialty service at once. Select one representative pathway, such as a new suspected PROS referral, a procedure requiring several specialties, a person receiving targeted therapy across sites, or a pediatric-to-adult transfer. Include patients or caregivers, frontline staff, and every team that sends or receives work. Choose a scope important enough to matter and small enough to test.

During days 1 through 30, listen and map. Name an executive sponsor, clinical lead, operational owner, and patient or family partners. Trace the pathway from the first question through accepted follow-up. Review a small set of recent cases, including at least one that went well and one with delay or rework. Identify where records, decisions, responsibility, or access break down. Baseline only the measures needed to understand that problem.

During days 31 through 60, design and test. Define the entry point, minimum information, accepting owner, acknowledgment, escalation, and closure signal. Create or refine the shared summary, multidisciplinary review, pre-procedure huddle, monitoring plan, or transition checklist that addresses the selected gap. Test it with representative users, including someone who does not already know the informal route. Check language, disability access, privacy, and the workload added to frontline teams.

During days 61 through 90, implement and verify. Launch on a limited scale, review exceptions frequently, and correct failure modes before expansion. Compare the new process with the baseline and ask people whether navigation burden changed. Document remaining dependencies, especially external specialty capacity, coverage, travel, laboratory capability, and information exchange. Report what changed, what did not, and what requires executive action after the observance window.

The lasting product should be a clearer route, not a one-day campaign artifact. Keep the pathway owner, exception review, and patient partnership active. Revisit the evidence as new studies and regulatory information emerge. Maintain the approved hero and public observance identity, while allowing the operating model to improve as experience grows. Awareness has done its work when fewer people are lost between expertise, fewer decisions are made with incomplete information, and families spend less energy coordinating a system that can coordinate itself.