Standalone NF1: guiding the transition from paediatric to adult care

Abstract

This report summarizes expert and patient-representative perspectives from the meeting entitled ‘Standalone NF1: guiding the transition from paediatric to adult care’, held in Madrid on October 2, 2025. Its primary objective was to examine clinical, organizational and patient-related challenges during transition and identify practical measures to improve continuity of care. Discussions focused on multidisciplinary co-ordination, case management, patient autonomy and structured transition pathways. NF1 characteristics, plexiform neurofibroma burden, surgery, and the currently approved MEK inhibitors selumetinib and mirdametinib, are summarized only for clinical context; selumetinib is discussed in greater detail because it was the treatment available at that time and the one addressed during the meeting.

PLAIN LANGUAGE SUMMARY

What is NF1 and why does it matter across the lifespan?

Neurofibromatosis type 1 (NF1) is a genetic condition that can cause changes in the skin, bones, nervous system and other organs. Many people develop benign tumours along nerves, called neurofibromas. Plexiform neurofibromas (PNs) can be present from early life and may cause pain, disfigurement, functional problems (for example, with vision, bladder, bowel or breathing) and, in some cases, a risk of malignant transformation. Because NF1 manifestations appear and change from childhood into adult life, patients need lifelong follow-up and multidisciplinary care.

How are PNs treated today?

Until recently, surgery was the only effective treatment for symptomatic PNs but many tumours are difficult or unsafe to remove completely. Two oral MEK inhibitors, selumetinib and mirdametinib, are now approved in the United States and European Union for symptomatic PNs for which surgery is not considered an appropriate option or for which complete surgical removal is not feasible. These treatments can shrink or stabilize tumours and may improve symptoms and functioning. Because the Meeting presentations focused on selumetinib, this report describes its clinical evidence, safety and practical use in greater detail. Surgery remains important for selected patients, and pharmacological and surgical approaches may be combined according to individual needs.

Why is the transition from paediatric to adult care so important in NF1?

Adolescence is a critical period in NF1. It often coincides with increasing visibility of cutaneous neurofibromas, persistent or newly recognized morbidity related to pre-existing PNs, cognitive and psychosocial challenges, and transfer from paediatric to adult services. Paediatric care is usually personalized and family-centred, whereas adult care is more fragmented and may lack specific transition pathways. This change can generate anxiety for patients and caregivers, who must adapt to new teams, new settings and greater expectations for self-management. Poorly planned transition can disrupt follow-up and negatively affect quality of life.

How can transition be improved?

This Meeting Report highlights the need for multidisciplinary teams, case managers and clearly defined care pathways to keep patients at the centre of decision-making. It summarizes practical recommendations arising from the Meeting. Separately, the Bridging the Gap document is presented as an example of a structured initiative that includes basic and advanced standards for hospitals, a practical checklist and recommendations organized before, during and after transfer to adult care.

Introduction

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder that affects 1 in 3000 live births (ranging from 1:1,141 to 1:4436 depending on the study), making it one of the most common genetic diseases.1,2 It is characterized by a broad spectrum of manifestations, including café-au-lait macules, axillary or inguinal freckling, skeletal and soft-tissue abnormalities, cognitive and behavioural impairments, and the development of multiple nerve sheath tumours known as neurofibromas.3 As these manifestations and their associated surveillance and treatment needs evolve throughout life, NF1 requires continuous, multidisciplinary care from childhood into adulthood.

The transition from paediatric to adult healthcare is a particularly vulnerable stage in the NF1 care pathway. Adolescents and young adults must adapt to new healthcare professionals and organizational structures while progressively assuming greater responsibility for appointments, surveillance, treatment and self-care. At the same time, adult services may be more fragmented, may have less experience with rare diseases, and may not offer the same degree of family-centred co-ordination as paediatric care. Clinical complexity, cognitive or psychosocial difficulties, administrative barriers and inadequate transfer of information may therefore compromise continuity of care.

This period may also coincide with an increasing number and visibility of cutaneous neurofibromas, persistent or newly recognized morbidity related to pre-existing plexiform neurofibromas (PNs), and relevant cognitive, functional and psychosocial needs. However, PNs are generally congenital or arise during early childhood, and their growth potential is greatest in younger children and usually decreases with age; available longitudinal evidence has not shown that puberty accelerates their growth.4,5 These clinical and organizational factors make carefully planned transition particularly important in NF1.

This report summarizes the key outcomes of an expert meeting entitled ‘Standalone NF1: Guiding the transition from paediatric to adult care’, held in Madrid, Spain, on October 2nd, 2025. The meeting was endorsed by the Association of People Affected by Neurofibromatosis (Asociación de Afectados de Neurofibromatosis) and supported by Alexion, AstraZeneca Rare Disease. It was chaired by Dr Héctor Salvador (Barcelona, Spain) and Dr Ignacio Blanco (Badalona, Spain).

The primary objective of the meeting and of this report was to examine the clinical, organizational and patient-related challenges of transition from paediatric to adult NF1 care, identify relevant unmet needs and discuss practical strategies to improve continuity, co-ordination and patient autonomy. Particular attention was given to multidisciplinary models, case management, administrative pathways, preparation for self-management, communication between paediatric and adult teams, and the perspectives of patients and caregivers. The clinical characteristics of NF1, the burden of PNs and current surgical and pharmacological treatments are also summarized to provide the background needed to understand why transition is especially complex in this population. These sections are intended as clinical context and not as a comprehensive or systematic review of NF1 manifestations or treatments; they present the clinical and scientific discussions arising from the expert meeting, in which the available evidence was reviewed and complemented by the experts’ clinical experience and professional opinions.

The meeting agenda and discussion topics were predefined by the scientific chairs in consultation with the participating experts. Topics were selected to address the main clinical, organizational and patient-related challenges associated with transition from paediatric to adult NF1 care, along with the clinical background needed to understand these challenges. Presentations were assigned according to the participants’ areas of expertise, and the subsequent multidisciplinary discussion included contributions from healthcare professionals and patient representatives. No formal consensus methodology, systematic literature review or Delphi process was undertaken; this report provides a narrative synthesis of the meeting presentations and discussions, complemented by selected relevant literature.

Characteristics of NF1

NF1 is an autosomal dominant disorder caused by a heterozygous germline pathogenic variant in the NF1 gene located on chromosome 17. This gene encodes neurofibromin, a tumour suppressor that negatively regulates the RAS–RAF–MEK–ERK signalling pathway. Reduced neurofibromin function contributes to the constitutional NF1 phenotype, including skeletal, neurological, cognitive and behavioural manifestations, but the germline variant alone does not fully explain the marked phenotypic variability of the disorder.6,7 NF1-associated tumours generally develop after somatic inactivation of the remaining functional NF1 allele in a susceptible cell lineage, consistent with Knudson’s two-hit model. Additional somatic alterations and interactions between neoplastic cells and the tumour microenvironment contribute to tumour development, progression and, in some cases, malignant transformation.6,7

Clinical manifestations and diagnosis

NF1 is highly heterogeneous, with marked inter- and intrafamilial variability, making it difficult to predict the clinical course in an individual patient (Figure 1).8 Nevertheless, many manifestations follow age-related patterns. Café-au-lait macules and some skeletal lesions may be present at birth and tend to become more evident during early childhood.9 Axillary or inguinal freckling often appears after café-au-lait macules during the first years of life.10 Optic pathway gliomas typically develop during early childhood, with most cases diagnosed before 6–7 years of age, although they may occasionally be identified later.9,11 Scoliosis commonly becomes apparent during childhood or adolescence.9,12 Cutaneous neurofibromas generally emerge around puberty and continue to increase in number throughout adult life.9,13 Malignant peripheral nerve sheath tumours (MPNSTs) occur predominantly during adolescence or adulthood.9,14 Lisch nodules may be detected during adolescence and increase in prevalence with age, being present in most adults with NF1. By contrast, choroidal abnormalities detected using near-infrared imaging may appear earlier and are more frequent than Lisch nodules in paediatric populations.3,9,15

Figure 1.

Clinical manifestations and symptoms of neurofibromatosis type 1.

Before 2021, NF1 diagnosis relied on the 1988 NIH consensus criteria, as reflected in British, French and other international guidelines.16–20 In 2021, these criteria were revised to incorporate genetic testing and choroidal abnormalities, improve the differentiation of NF1 from Legius syndrome in individuals with overlapping pigmentary manifestations, and establish specific diagnostic criteria for mosaic NF1 (Box 1).3 Molecular testing may also support diagnosis in young children whose phenotype is not yet fully expressed but it is not required when the clinical diagnostic criteria are fulfilled.3

Box 1. Diagnostic criteria for NF1.

≥1 of the following, in an individual WITH a parent with NF1 ≥2 of the following, in an individual WITHOUT a parent with NF1

≥6 Café-au-lait macules with the following sizes: >0.5 cm in prepubertal individuals >1.5 cm in postpubertal individuals

Axillary or inguinal freckles

≥2 neurofibromas of any type or 1 plexiform neurofibroma

Optic pathway glioma

≥2 Lisch nodules or ≥2 choroidal abnormalities

One distinctive osseous lesion, such as: Sphenoidal dysplasia Anterolateral bowing of the tibia Pseudoarthrosis of a long bone

A heterozygous pathogenic NF1 variant, with a variant allele fraction of 50% in apparently normal tissues such as white blood cells

NF1, neurofibromatosis type 1.

For practical purposes, NF1-associated neurofibromas may be broadly grouped into cutaneous neurofibromas, discrete subcutaneous or deep nodular neurofibromas and PNs.9,13,21 These categories are clinically useful but are not necessarily mutually exclusive, particularly for PNs, which show considerable morphological and anatomical heterogeneity. There is no universally agreed definition of PN, and current imaging-based approaches characterize PNs according to their morphology, depth, relationship to the involved nerve and interface with surrounding structures. PNs may therefore be superficial, deep, or have both superficial and deep components.21 Accordingly, the adjective ‘internal’ is not used in this report as a formal neurofibroma classification term. It is retained only when reproducing the terminology of studies that specifically assessed MRI-detected internal tumour burden.

Cutaneous neurofibromas are confined primarily to the skin and frequently have a substantial aesthetic and psychosocial impact.13 Sub-epidermal glial cells have been proposed as a possible cellular origin of cutaneous neurofibromas, but this remains a leading hypothesis rather than an established fact.22 PNs grow along a nerve and its branches, frequently involving multiple fascicles and adjacent tissues.21 In neurofibromas, biallelic NF1 inactivation occurs in the neoplastic Schwann cell lineage, whereas other NF1-haploinsufficient and wild-type cells contribute to the heterogeneous tumour microenvironment.6,7

PN diagnosis is generally based on clinical assessment and MRI findings in an individual with NF1. Biopsy is not routinely required and should be reserved for lesions with clinical or imaging features that raise concern for atypical transformation or malignancy.21,23 Distinct nodular lesions are an MRI-defined phenotype that usually develop within or adjacent to a PN and show growth characteristics that differ from those of typical PNs.24 They generally appear as well-demarcated nodules, often measuring ≥3 cm, and lack the central target sign frequently observed in typical PNs.24 Some distinct nodular lesions may correspond histologically to atypical neurofibromatous neoplasm of uncertain biologic potential, which are considered potential precursor lesions on the pathway to MPNSTs; however, imaging findings alone cannot establish the histopathological diagnosis.21,24

Symptoms, burden and growth dynamics

PNs are identified clinically in approximately 30% of individuals with NF1 and in around 50% when whole-body MRI is used, reflecting the detection of lesions that may not be apparent on clinical examination.9,21 These estimates describe the frequency of PNs and should not be conflated with the frequency of PN-related symptoms. Nevertheless, PNs can cause substantial morbidity. In selected referral and natural history cohorts of children and young adults with established, clinically significant PNs, reported tumour-related morbidities included disfigurement, pain, motor and other functional impairments, and complications related to tumour location, compression, haemorrhage or malignant transformation.21,25,26 Symptomatic PNs are common in locations where resection is difficult, and recurrence is likely, such as the head and neck, whereas abdominal PNs are more often asymptomatic.23,27 In the paediatric referral cohort reported by Prada et al., age at PN identification showed a bimodal distribution, with 52% identified from birth to 3 years of age and 22% between 11 and 18 years.27 This finding describes the age at clinical identification in a selected cohort and should not be interpreted as evidence of puberty-related acceleration of PN growth, which has not been demonstrated in longitudinal studies.4,5

The burden of NF1 extends beyond physical symptoms. Aesthetic, functional and cognitive manifestations affect patients and caregivers across psychological, social and economic domains.28 In paediatric NF1 PN, caregiver burden includes physical and emotional overload, loss of work productivity and disruption of daily activities.28 In adults, NF1-related morbidity can reduce independence, interfere with daily functioning, impair quality of life and generate indirect costs through work absences and travel to specialized centers.29–32 These aspects are particularly relevant during transition, when adolescents and young adults are expected to assume increasing responsibility for a disease that remains clinically complex and unpredictable.

PN growth is highly variable. At the individual lesion level, periods of rapid growth may be followed by relative stability, and no biomarker is currently available to predict the course of a given PN.16,24 In children up to approximately 10 years of age, PN growth may exceed body-weight gain.24 In adults, the Boston cohort longitudinally assessed MRI-detected internal neurofibromas, including PNs. After 10 years of follow-up, 63% of the MRI-detected internal neurofibromas and 56% of PNs had decreased in volume, whereas 17% of all tumours grew; regression and growth could coexist in the same patient.33 No clear correlation was found between tumour growth and age, sex, genotype, pregnancy, hormonal contraception or menstrual cycle length.33

A major concern is malignant transformation into MPNSTs (Figure 2).34 Although most neurofibromas remain benign, 8–16% of patients may develop malignancy at any age but are usually diagnosed between the ages of 20 and 40 years.35 New persistent or increasing pain, rapid growth or change in a known mass, and new neurological symptoms should raise clinical suspicion of malignancy.34,35 Because malignant transformation may take years and may pass through a phase of atypical neurofibromatous neoplasm of uncertain biologic potential, appropriate surveillance is essential. Current clinical guidelines recommend considering whole-body MRI at transition from childhood to adulthood to assess tumour burden and support risk stratification.35

Figure 2.

Malignancy progression of a neurofibromatosis type 1 tumour.

Malignant progression may arise from a plexiform neurofibroma with biallelic NF1 inactivation. Loss or inactivation of CDKN2A/B is associated with progression to ANNUBP, whereas additional alterations involving the PRC2 components SUZ12 or EED contribute to MPNST development.

ANNUBP, atypical neurofibromatous neoplasm of uncertain biologic potential; MPNST, malignant peripheral nerve sheath tumour; pNF, plexiform neurofibroma.

Reproduced courtesy of Dr Miriam Magallón Lorenz from: Magallón Lorenz M. Integrative genomic analyses of malignant peripheral nerve sheath tumors. Universitat de Barcelona; 2023. https://tdx.cat/handle/10803/689064?show=full

Treatment of PNs

Until 2023, PNs were treated with a variety of drugs, such as interferon, imatinib or everolimus, but none provided consistent clinical benefit. Consequently, surgery was historically the only effective treatment recommended by European clinical practice guidelines and by the Spanish Paediatric Association protocol for symptomatic PNs.16,36–38 The objective of surgery is to reduce tumour volume and relieve morbidity, including pain, disfigurement, compression and functional impairment. However, complete resection is often not feasible. Up to 80% of PNs may be considered inoperable or not amenable to intervention because of tumour size, location, infiltration of adjacent structures, risk of haemorrhage or neurological damage, and expected functional or aesthetic sequelae.39 For patients with inoperable PNs, management was previously limited to symptomatic treatment without modifying tumour growth.39

Since 2023, clinical guidelines have recommended MEK inhibitors for symptomatic, inoperable PNs, reflecting the growing evidence supporting pathway-targeted therapy in NF1.35 At the time of manuscript revision, selumetinib and mirdametinib were the two MEK inhibitors approved by both the FDA and the EMA for NF1-associated symptomatic PNs that are inoperable or not amenable to complete resection. Selumetinib is approved in the USA and in the European Union for adults and paediatric patients aged ≥1 year with symptomatic, inoperable PNs, with additional formulation developments intended to facilitate treatment in younger children and patients with swallowing difficulties.40–44 Mirdametinib is approved in the USA and European Union for adults and paediatric patients aged ≥2 years with symptomatic PNs that are not amenable to complete resection or cannot be surgically removed.45,46

The meeting presentations specifically addressed selumetinib, which was the first MEK inhibitor approved for paediatric NF1-associated PNs and has accumulated long-term clinical experience in this setting.47 Accordingly, this meeting report provides a brief overview of both currently approved MEK inhibitors but discusses selumetinib in greater detail to reflect the content of the meeting. The manuscript is not intended as a comparative review of selumetinib and mirdametinib.

Selumetinib: mechanism, efficacy and safety

Selumetinib is an orally administered selective MEK1 and MEK2 inhibitor. By inhibiting MEK1 and MEK2, it prevents overactivation of the RAS–RAF–MEK–ERK pathway caused by neurofibromin dysfunction, thereby reducing tumour cell proliferation and survival.6,7,48,49 In Europe, selumetinib monotherapy is indicated for paediatric patients aged ≥3 years with NF1 and symptomatic, inoperable PNs.50 In the USA, it is indicated for paediatric patients aged ≥2 years with NF1 who have symptomatic, inoperable PNs, with subsequent regulatory updates expanding access.40–42,51

The efficacy of selumetinib has been demonstrated in paediatric and adult studies. In the paediatric phase I study, 24 patients aged 3–18 years received selumetinib twice daily in 28-day cycles; the maximum tolerated dose was 25 mg/m², and 71% achieved a partial response, defined as ≥20% PN volume reduction for at least 4 weeks.48 In the phase II SPRINT Stratum 1 trial, 50 children and adolescents aged 2–18 years with symptomatic, inoperable NF1 PN received selumetinib 25 mg/m² twice daily;52 68% achieved ≥20% PN volume reduction, and 82% of responders maintained response for at least 1 year. Median time to response was 7.2 months and median time to maximal tumour shrinkage was 14.6 months. Three years after treatment initiation, median progression-free survival had not been reached, whereas it was 1.3 years in the age-matched natural history cohort. Clinical benefits were also observed, including improvements in quality of life, pain, strength and range of motion.52 Long-term follow-up of the two trials confirmed the durability of these effects, with sustained improvements in tumour-related pain and pain interference through cycle 48.53

In adults, a phase II study reported an objective response rate of 63.6% and a median maximal PN volume reduction of 23.6%, together with reductions in tumour pain intensity and interference.54 The phase III KOMET trial further demonstrated benefit in adults, with a median time to response of 3.7 months and an objective response rate of 20% at cycle 16 compared with 5% for placebo, accompanied by improvements in pain and quality of life.55

The most frequent adverse reactions in the paediatric SPRINT studies were vomiting, diarrhoea, elevated blood creatine phosphokinase, nausea, dry skin, fever, acneiform dermatitis, paronychia and stomatitis.50 Grade ≥3 events included diarrhoea, paronychia, vomiting, elevated blood creatine phosphokinase, pyrexia and acneiform dermatitis.50 Most adverse events were manageable with supportive care, monitoring and dose modifications, and did not usually require permanent discontinuation.52 Because some adverse events may occur years after treatment initiation, continuous monitoring is essential, particularly in patients treated from childhood into adolescence and adulthood.53 Table 1 summarizes practical recommendations for managing selected adverse events.56

Table 1.

Recommendations for managing selected adverse events related to selumetinib.56

Paronychia
Prevention	Prevent possible trauma to hands and feet and receive advice on nail care To prevent further episodes, consider referral to a specialist Offer psychosocial support to reduce compulsive behaviour such as nail biting
Any degree of infection	The affected nail should be softened with an antiseptic bath twice a day The infection should be treated with an antiseptic, with or without a topical antibiotic
Grade 2	High-potency corticoids (topical) once infection has been ruled out Systemic antibiotics in case of infection Consider reducing the dose or discontinuing treatment
Grade 3	Consult an expert podiatrist or consider surgical treatment If there is pus, antibiotics (tailored to the bacteria identified) in combination with a topical or systemic corticoids (to be used as a standalone treatment once infection has been ruled out) Consider reducing the dose or discontinuing treatment
Eczematous eruptions
Prevention	Moisturize with emollient twice a day Avoid excessive sun exposure or wear protective clothing in the sun
Symptomatic	Use a low-potency topical corticoid
With pruritus	Add an antihistamine agent
Persistent	Switch to a stronger topical corticoid Consider reducing the dose or discontinuing treatment
Persistent on the scalp	Consider using liquid or foam corticoids or coal tar shampoos
Gastrointestinal (stomatitis, nausea, vomiting)
Prevention	Brush teeth twice a day, brush the tongue and replace toothbrushes every 3 months Inspect the mouth for stomatitis Avoid fried, fatty and high-salt foods; consider consulting a dietitian
Early-stage stomatitis	Analgesics or topical nystatin
Nausea/vomiting	Antiemetics or dietary changes
Gastritis	Proton pump inhibitors (excluding omeprazole)
Painful stomatitis	Gels for oral mucositis Painful mouth ulcers can significantly affect daily life

Real-world evidence of selumetinib and integration with surgery

In addition to pivotal trials, real-world studies support the clinical usefulness of selumetinib. A sub-analysis evaluating spinal neurofibromas showed improvement in 18 of 24 patients, with no progression detected during treatment.57 A single-centre study in Portugal suggested that combining selumetinib and surgery may stabilize tumour size and reduce pain and functional impairment.58 A multicentre Italian study in 70 patients with inoperable, symptomatic NF1 reported stable disease or partial response in 94.1% at 6 months and 91.5% at 12 months, together with reductions in pain and improvements in quality of life and ECOG performance status.59

Despite the availability of MEK inhibitors, surgery remains essential in selected patients. Surgical goals include reducing tumour burden, relieving compression, improving pain and function, enhancing cosmetic outcomes, and minimizing the risk of malignant degeneration.21,39,60,61 However, surgery is technically challenging because PNs often infiltrate adjacent structures, recur after incomplete resection and may be associated with postoperative complications.21,39,60,61

The arrival of selumetinib has created opportunities for combined treatment strategies. In non-operable tumours, selumetinib may reduce tumour size, improve symptoms and enhance quality of life. Preoperative treatment may facilitate surgery by shrinking the tumour and reducing the need for aggressive procedures, whereas postoperative use may help control residual disease, reduce regrowth and decrease the need for repeated interventions.21,58,60 These strategies require individualized risk–benefit assessment, especially in asymptomatic patients, in whom close monitoring may be preferable until symptoms, deformity or clinically relevant progression appear.

The transition process in NF1

NF1 is a rare, multisystem disease that requires lifelong, multidisciplinary care. Clinical manifestations change over time, and patients frequently move between different specialists and care settings, making the transition from paediatric to adult care particularly challenging. Transition should therefore be understood as a structured, planned process rather than as a single event, with the patient and family at the centre of care. During the meeting, this issue was addressed from a clinical and administrative perspective, as well as from the perspective of patients and caregivers. Figure 3 shows the timeline of the six basic elements of transition. With a structured transition plan, more positive outcomes can be achieved.62,63

Figure 3.

Timeline of the six basic elements of healthcare transition.

Transition from a clinical perspective

Because NF1 has numerous and evolving manifestations, care often involves multiple specialties, which can lead to fragmentation and patients ‘living’ in the hospital. Multidisciplinary teams, in which each specialist contributes their expertise to a unified clinical assessment, are essential to minimizing this fragmentation and to provide coherent, longitudinal care.

Clinical manifestations of NF1 appear throughout life, from birth to adulthood, so it is neither realistic nor sufficient to rely on a single diagnostic or therapeutic decision. Adolescence is a particularly critical period, as major aesthetic and cognitive changes coincide with the transfer from paediatric to adult services. Paediatric medicine is typically characterized by personalized, comprehensive care in a familiar environment and by stable, long-term relationships between families and healthcare professionals. In contrast, adult care is often more fragmented, with dispersed services and a lack of specific transition policies, which can jeopardize continuity of care.

Transition is intended to prepare and transfer paediatric patients from supervised care to adult units, where they will progressively assume responsibility for self-care. This process should be planned, anticipated and co-ordinated in a gradual manner, in line with the patient’s maturity rather than based on a rigid chronological age. A well-planned transfer improves prognosis and increases the likelihood that patients will remain in follow-up. Although guidelines such as GENTURIS provide recommendations for follow-up and transition, there is currently no single, validated model for healthcare transition in NF1.35 Given the complexity of NF1 and its lifelong monitoring needs, involvement of a specialized multidisciplinary team is recommended whenever possible; where this is not available, an adult NF1 expert should be identified to co-ordinate referrals to other specialists.64

Transition from an administrative/organizational perspective

From an organizational standpoint, the healthcare system must provide tools that enable truly integrated care. One key element is the figure of a Case Manager, acting as a link between the patient, the family, and the multidisciplinary team and serving as a clear point of contact for all parties. Care pathways for rare diseases such as NF1 should not be segmented into isolated blocks (detection, diagnosis, treatment and follow-up) but should instead be designed as a sequence of co-ordinated actions and decisions that collectively address patients’ needs over time.

In practice, transition may be hindered by limited capacity in adult services, competing demands on resources, and the complexity associated with chronic complications and long-term treatments.62,65,66 To support centres wishing to care for patients with NF1, the Spanish Society for Healthcare Quality (SECA) has developed a standard that allows institutions to assess their level of competence and identify areas for improvement.67

Transition from the patient and caregiver perspective

For patients and families, NF1 poses challenges at personal, social and logistical levels. Because the condition often requires multiple specialist visits, patients and caregivers may feel that they spend much of their lives in the hospital. Patient associations therefore advocate for a truly patient-centred model, in which specialists ‘come to the patient’ through co-ordinated, multidisciplinary clinics rather than requiring patients to navigate complex systems alone.

The transition from paediatric to adult care is a source of significant anxiety for both patients and caregivers. Differences between care models (personalized paediatric care versus more fragmented adult services), lack of clear information on what to expect, and uncertainty about who will assume responsibility for follow-up all contribute to fear and insecurity. In this context, healthcare professionals must not only be proficient in the diagnosis and management of NF1 but also skilled at supporting patients and families through this vulnerable phase, addressing emotional as well as medical needs.

A real-world example of transition

A clinical case discussed during the meeting illustrates how the transition from paediatric to adult care in NF1 is not merely a change of physician but a complex process in which clinical needs, administrative co-ordination, patient autonomy and geographic barriers intersect. The case involved a young man with NF1 and PNs who had been followed in paediatric care and treated with selumetinib for neuropathic cervical pain. During the paediatric stage, treatment was initiated in a highly specialized centre, but it had to be discontinued after several months because of difficulties in completing the required monitoring visits and tests.

After transition to adult care, the patient was referred to an adult oncology unit, and selumetinib was restarted. However, the first months after transfer showed several of the typical vulnerabilities of this period. The patient often attended visits alone, missed scheduled appointments and did not undergo planned MRI studies. Some imaging tests were cancelled or performed in another region, and the adult team was unable to access the images for comparison. As a result, clinical decisions had to rely mainly on symptoms and telephone follow-up rather than on complete longitudinal radiological assessment. Treatment was interrupted on more than one occasion for approximately 2 months, and each interruption was associated with worsening pain. Conversely, when selumetinib was restarted, the patient again reported clinical improvement.

This case highlights several practical lessons. First, transition requires much more than referral from a paediatric specialist to an adult specialist. The adult team must receive a structured clinical summary, including diagnosis, previous complications, current tumour burden, treatment history, adverse events, monitoring needs and pending tests. Second, radiological continuity is essential in NF1, particularly in patients with PNs or other deep-seated neurofibromas, because comparison with previous whole-body or regional MRI studies is often needed to distinguish stability, progression or suspicious change. Third, treatment adherence and follow-up attendance cannot be assumed simply because the patient has reached legal adulthood. Some young adults with NF1 may have cognitive, emotional, social or logistical difficulties that affect their ability to organize appointments, collect medication, attend imaging studies or communicate clinical changes.

The case also illustrates the administrative dimension of transition. Patients who live far from expert centres, or who move between regions for family, educational or work reasons, may face fragmented care, duplicated appointments and incomplete information transfer. A case manager or transition co-ordinator could help schedule visits, ensure that imaging is performed and shared appropriately, maintain communication between local and expert centres, and provide a stable point of contact for the patient and family. This is aligned with the view expressed by specialists and patient representatives that patients with NF1 should not be required to navigate the healthcare system alone.

Finally, the evolution of the patient also shows the importance of progressive empowerment. By 2025, the patient retained clinical improvement, had mild, manageable toxicity, and was beginning nursing studies in Madrid, hoping this would allow better attendance at follow-up visits. This reinforces the goal of transition: not only to maintain treatment and surveillance but also to help the young adult incorporate NF1 care into an independent life plan, with adequate professional support and without losing continuity.

Recommendations for improving the transition in NF1: the Bridging the Gap initiative

During the meeting discussion, several recommendations emerged to assist in planning the transition in NF1 to maintain continuity of care throughout adulthood.62,65,66 These are described below:

• Identify patients at high risk who may require additional support during transition.

• Recognize transition as a continuous process, starting well before transfer and extending beyond the first adult visits.

• Acknowledge NF1 as a progressive disease that may require proactive surveillance and intervention during adulthood.

• Prioritize patient education on self-management, follow-up schedules and screening recommendations.

• Inform patients about hereditary risk, including the possibility of transmitting NF1 to their children.

• Provide training for adult-care professionals on the specific needs of adults with NF1.

Separately from the recommendations arising from the meeting, the Spanish recommendation document, Bridging the Gap: Recommendations for the Transition of Patients with Neurofibromatosis Type 1, provides an example of a structured initiative aimed at improving the transfer of patients with NF1 from paediatric to adult care.68 Its objectives are to improve management during transition, strengthen co-ordination between healthcare professionals, patients and families, and support healthcare decision-making throughout the process. The document was developed through three multidisciplinary working groups that included professionals involved in paediatric NF1 care, specialists responsible for adult care, and patients with NF1 and their families. The resulting recommendations are organized chronologically according to the periods before, during and after transfer. They are also classified into two levels of implementation: basic recommendations, intended to be applicable in any hospital, and advanced recommendations for centres with greater experience and resources. A practical checklist was additionally developed to support follow-up of the transition process, covering key clinical information, clinical variability, patient competencies, co-ordination between paediatric and adult teams, institutional co-ordination, emotional preparation, psychosocial needs and progressive autonomy.68

The point of view of the patient with NF1

To understand the characteristics of patients with NF1 and the perspectives of both patients and caregivers on the impact of the disease, a study was conducted in Spain and Portugal.69 It describes how NF1 significantly affects the physical, emotional, and social quality of life of both patients and caregivers. Although they are generally satisfied with the healthcare they receive, they raise some points for consideration. On the one hand, patients consider pain to be one of the most relevant symptoms, which raises the question of whether healthcare teams are prepared to deal with it effectively. On the other hand, caregivers reported experiencing deterioration in their quality of life due to physical and emotional overload. The main unmet need in the approach to the disease was the need for more comprehensive management strategies, including psychosocial support and better co-ordination amongst specialists.69

During the meeting, a 21-year-old patient with NF1 participated and shared his experience with the disease because he was diagnosed at 4 months of age. He described that patients’ perceptions of the disease vary depending on their age and individual circumstances. For example, adolescents express great concern about the difficulty of concentrating on their studies, pain and fatigue, not to mention the repercussions of the numerous surgical procedures they undergo. In any case, they greatly value receiving an early diagnosis so that treatment can begin as soon as possible. He explained that, since many of the patients have lived with the disease since birth and have internalized their situation, they do not usually experience a significant impact on their quality of life. Most importantly, each person must be able to cope with the aspects that affect them the most, such as a limp or a vision problem, and be surrounded by an environment in which the disease is not treated as a taboo that should be avoided. In his case, he confronted the disease with his family openly, which has allowed him to deal with the disease comfortably.

One of the main problems reported by the patient during the transition process was dealing with the overwhelming bureaucracy involved in the process and finding the appropriate healthcare professionals who are aware of the type of disease he has, given the low awareness due to its status as a rare disease. For him, the role of patient associations is fundamental, as they not only allow patients to form a community but also provide a vital network of information and support. Furthermore, he believes that this flow of information is useful not only for patients but also for healthcare professionals, allowing them to learn about other cases.

The patient shared the following message: do not let the family and patient bear the entire burden of the illness alone – offer them information on how to take the next steps, not just what steps they need to take.

Conclusions

NF1 is a lifelong, multisystem disorder requiring continuous multidisciplinary care from childhood into adulthood. PNs can cause substantial morbidity through pain, disfigurement, functional impairment and, in selected cases, malignant transformation. Their management now includes surgery and the approved MEK inhibitors selumetinib and mirdametinib for symptomatic tumours that are inoperable or not amenable to complete resection. Because the meeting presentations focused on selumetinib, its clinical evidence and practical use are discussed in greater detail; this report is not intended as a comparative review of the two agents.

The central message of this meeting report is that transition from paediatric to adult NF1 care should be regarded as a planned, progressive process rather than a single transfer event. Clinical complexity, fragmented adult services, administrative barriers and the growing expectation of patient autonomy can compromise surveillance, treatment adherence and continuity of care. Multidisciplinary teams, structured transfer summaries, case management, co-ordinated access to imaging and progressive preparation for self-management are therefore essential.

The recommendations arising from the meeting, together with independently developed resources such as the Bridging the Gap document, provide complementary approaches for translating transition principles into routine practice. Their implementation and evaluation may support a more integrated, proactive and patient-centred continuum of NF1 care across the lifespan.