Neurofibromatosis 1 microdeletion syndrome is a rare genetic condition where a small piece of chromosome 17, including the NF1 gene and nearby genes, is missing. This missing piece is called a “microdeletion.” Because several important genes are lost together, the person usually has a more severe form of neurofibromatosis type 1 (NF1) than people who have only a small change inside the NF1 gene. Children and adults with this syndrome often have learning problems, developmental delay, many skin tumors called neurofibromas, special facial features, and a higher chance of certain cancers.
Neurofibromatosis 1 (NF1) microdeletion syndrome is a special form of NF1 caused by a tiny missing piece of DNA (a “microdeletion”) on chromosome 17q11 that removes the NF1 gene and several neighbouring genes at the same time. This leads to a more severe version of NF1 with earlier and more numerous skin spots (café-au-lait macules), many cutaneous and plexiform neurofibromas, learning and behavioural problems, distinctive facial features, skeletal abnormalities, and a higher risk of tumours than in typical NF1.1
Because extra genes are deleted, people with NF1 microdeletion syndrome often have developmental delay, intellectual disability, attention-deficit/hyperactivity disorder (ADHD), autistic features, larger head size, and more aggressive tumour growth than people with NF1 caused by a simple point mutation. Regular specialist follow-up is therefore very important to detect complications like plexiform neurofibromas, optic pathway gliomas, scoliosis, vascular problems and possible malignant peripheral nerve sheath tumours (MPNSTs) early.2
Doctors now see NF1 microdeletion syndrome as a specific subtype of NF1, not a separate disease. It is found in about 4–5% of all people who have NF1. The NF1 gene region lies on chromosome 17 at position 17q11.2. In this syndrome, a piece of about 1 to 1.5 million DNA “letters” (1–1.5 Mb) is missing, and this affects many genes at once. This wide loss of genetic material explains why people with NF1 microdeletion syndrome usually have more serious symptoms and more medical complications than people with small NF1 gene variants.
Other names
Neurofibromatosis 1 microdeletion syndrome has several other names. These names often describe the deleted chromosome region or the size of the missing piece. Understanding these names is helpful when reading reports or research papers, because they may use different labels for the same condition.
Other names
NF1 microdeletion syndrome
Chromosome 17q11.2 deletion syndrome, 1.4 Mb
17q11 microdeletion syndrome
NF1 large deletion syndrome
NF1 contiguous gene deletion syndrome
NF1 microdeletion (MIM #613576)
Researchers also describe types of NF1 microdeletions based on the exact size of the missing DNA and the breakpoints. This helps doctors and scientists study how different deletions may change symptoms and severity.
Types
Type-1 NF1 microdeletion – the most common type, about 1.4 Mb in size, with characteristic breakpoints and loss of about 14 genes including NF1.
Type-2 NF1 microdeletion – slightly smaller (~1.2 Mb), often associated with mosaicism (some cells have the deletion and some do not).
Type-3 NF1 microdeletion – about 1.0 Mb, rarer, with a different set of surrounding genes deleted.
Atypical NF1 microdeletions – deletions with variable size and borders, which may delete different combinations of genes around NF1.
Mosaic NF1 microdeletion – the deletion is present only in a part of the body’s cells; symptoms may be milder or more patchy.
Causes
Each “cause” below describes a factor or mechanism that leads to, or is related to, NF1 microdeletion syndrome. The main direct cause is the loss (deletion) of the NF1 region on chromosome 17; other points describe how and why this deletion can happen.
Deletion of the NF1 gene region on chromosome 17q11.2
The central cause of NF1 microdeletion syndrome is a missing piece of DNA in the 17q11.2 region that includes the NF1 gene and nearby genes. When this piece is deleted, the body makes too little functional neurofibromin, the protein made by NF1, and also loses other genes that help control growth and development. This combined loss leads to overgrowth of nerve sheath cells, skin changes, learning problems, and other features.Contiguous gene deletion (loss of many genes together)
NF1 microdeletion syndrome is called a “contiguous gene deletion” disorder because several genes lying next to each other are removed at the same time. The NF1 gene is one of them, but other genes such as RNF135 and others in the 17q11.2 region are also lost. The combined effect of losing multiple genes is thought to cause tall stature, overgrowth, facial differences, and more severe learning problems than classic NF1.Non-allelic homologous recombination (NAHR)
The chromosome 17q11.2 region contains repeated DNA blocks called low-copy repeats. During egg or sperm formation, these repeats can misalign and recombine in the wrong way. This process, known as non-allelic homologous recombination, can cut out the region between the repeats and create the microdeletion that causes NF1 microdeletion syndrome.De novo (new) mutations in the child
Most NF1 microdeletions arise “de novo.” This means the deletion is not present in either parent and appears for the first time in the child’s egg or sperm cell or early embryo. De novo events explain why many children with NF1 microdeletion syndrome are born to parents who do not have NF1.Inherited microdeletions from an affected parent
In some families, a parent has NF1 microdeletion syndrome and passes the same deletion to their child. Because NF1 is autosomal dominant, a child has a 50% chance to inherit the deletion when one parent carries it. These inherited cases may show similar features in several family members, although the exact severity can still vary.Germline mosaicism in a parent
Sometimes, a parent has the deletion only in some of their egg or sperm cells but not in their blood cells; this is called germline mosaicism. That parent may look healthy, but more than one child can be born with NF1 microdeletion syndrome. Doctors suspect germline mosaicism when multiple siblings are affected but parents test negative in blood.Loss of neurofibromin function
The NF1 gene instructs cells to make neurofibromin, which helps control RAS-MAPK signaling, a pathway that drives cell growth. When the NF1 gene is deleted, neurofibromin is missing, and cells grow and divide more than they should. This uncontrolled growth is a key biological cause of neurofibromas and tumor risk in NF1 microdeletion syndrome.Loss of growth-regulating genes such as RNF135
Genes next to NF1, including RNF135 and others, also help regulate growth, facial development, and brain function. Their deletion is thought to contribute to tall stature, macrocephaly (large head), and facial differences that are commonly seen in people with NF1 microdeletion syndrome but not always in classic NF1.Increased genetic dosage imbalance
Because a whole block of genes is missing, the balance between different signaling pathways in the cell is disturbed. This dosage imbalance can affect how nerves, bones, and blood vessels form and respond to normal signals, leading to skeletal problems, vascular issues, and more diffuse disease than with small NF1 variants alone.Chromosomal instability in the NF1 region
The NF1 region is considered a genomic “hot spot” that is prone to structural changes such as deletions and duplications. This instability makes it more likely that microdeletions will occur during cell division, especially in egg or sperm cells.Parental age–related risk (general chromosomal risk)
In many chromosomal disorders, increasing maternal or paternal age slightly raises the chance of new chromosomal changes. While specific data for NF1 microdeletions are limited, NF1 as a whole has a high rate of new mutations, and general genetic studies suggest that DNA errors during egg or sperm formation become more common with older parental age.Background NF1 mutation rate
The NF1 gene has one of the highest known spontaneous mutation rates among human genes. This high mutability contributes overall to the chance that structural errors, including large microdeletions, will happen in the NF1 region.Non-mosaic vs mosaic status
When all cells carry the deletion (non-mosaic), the phenotypic effect is stronger because every tissue is affected. This non-mosaic status is a cause of more severe symptoms compared with mosaic deletions where only part of the body carries the change.Interaction with other common genetic variants
People with NF1 microdeletion syndrome also carry many ordinary genetic variants that they inherit from their parents. These variants, in other genes that control learning, growth, or behavior, may modify how severe the symptoms become, causing variability between people with the same deletion.Epigenetic changes secondary to the deletion
Loss of the NF1 region can secondarily change how other genes are switched on or off (epigenetic regulation). These downstream changes may contribute to neurodevelopmental problems and tumor risk, even though the main event is the deletion itself.Environmental factors that affect tumor growth
While the deletion starts the condition, later environmental factors such as radiation exposure, tobacco smoke, or chronic inflammation may further increase the chance that benign neurofibromas turn into malignant tumors, especially in people already at high risk like those with NF1 microdeletion syndrome.Hormonal influences during growth and puberty
NF1 tumors often grow more quickly during times of rapid body change, such as puberty or pregnancy. In NF1 microdeletion syndrome, where tumor risk is already higher, these hormonal surges can act as triggers for tumor growth or symptom worsening.Vascular fragility from gene loss
NF1 affects the walls of blood vessels, and microdeletion cases may have more severe vascular changes. Loss of NF1 and neighboring genes in vessel cells can cause abnormal vessel structure and higher risk of vascular complications, such as aneurysms or stenosis, in some patients.Disrupted brain development
Because NF1 and surrounding genes play roles in brain development and synapse function, their loss can disturb how brain networks form. This is a biological cause of learning difficulties, attention problems, and sometimes seizures in NF1 microdeletion syndrome.Increased risk of secondary mutations in tumors
When tumor cells already lack NF1 due to the germline deletion, they need fewer additional changes to become malignant. This “first hit” from the microdeletion is a cause of increased risk for malignant peripheral nerve sheath tumors (MPNST) and other cancers in NF1 microdeletion syndrome.
Symptoms
Facial differences (dysmorphic facial features)
Many people with NF1 microdeletion syndrome have subtle but recognizable facial features. These can include wide-set eyes, broad or fleshy nose, coarse facial appearance, low-set ears, flat forehead, or a broad neck. These features are usually mild but are more frequent in microdeletion patients than in classic NF1, and they can help doctors suspect the diagnosis.Developmental delay in early childhood
Babies and toddlers with NF1 microdeletion syndrome often reach milestones such as sitting, walking, or talking later than other children. This developmental delay reflects the effect of the deletion on brain development and motor coordination, and it may be one of the first signs that brings the child to medical attention.Intellectual disability or learning difficulties
Many children with this syndrome have difficulties with learning, memory, attention, or problem solving. School problems and the need for special education are common. Intellectual disability can range from mild to moderate and is more frequent and often more severe than in typical NF1.Speech and language problems
Delayed speech, trouble pronouncing words, or problems understanding complex language are frequent. Children may need speech therapy to help with communication. These difficulties reflect both general developmental delay and specific effects of the deletion on language-related brain networks.Overgrowth, tall stature, and large hands/feet
Compared to many NF1 patients, people with NF1 microdeletion syndrome often show overgrowth. They may be taller than expected for age and family, have a larger head (macrocephaly), and have large hands and feet. This overgrowth pattern is characteristic for microdeletion cases and helps differentiate them from other NF1 forms.Numerous cutaneous and subcutaneous neurofibromas
Skin tumors called neurofibromas are a hallmark of NF1. In NF1 microdeletion syndrome, they often appear earlier in life and in larger numbers than in most classic NF1 patients. Subcutaneous neurofibromas under the skin can cause pain, nodules, and cosmetic concerns, especially during adolescence and adulthood.Plexiform neurofibromas and tumor burden
Plexiform neurofibromas are larger, more complex tumors that grow along nerves and can involve many tissues. People with NF1 microdeletion syndrome often have a higher whole-body tumor burden and more plexiform neurofibromas, which can cause disfigurement, pain, and, in some cases, malignant transformation.Café-au-lait spots and skin freckling
Like all NF1 patients, individuals with NF1 microdeletion syndrome have multiple café-au-lait macules (flat, light-brown skin spots) and freckling in areas such as the armpits and groin. These skin signs are often the earliest visible features and form part of the diagnostic criteria for NF1.Cognitive and behavioral problems
Attention-deficit/hyperactivity, anxiety, social difficulties, and autistic-like behaviors can occur. These problems reflect underlying changes in brain networks caused by the deletion. They can strongly affect school and social life and often require psychological and educational support.Seizures
Some patients with NF1 microdeletion syndrome have seizures. These may be linked to structural brain differences or cortical malformations. Seizures are not present in everyone, but they are reported more frequently in some chromosomal 17q11.2 deletion cohorts than in general NF1 populations.Bone and skeletal problems
Scoliosis (curved spine), bone cysts, and other skeletal abnormalities may occur. NF1 affects bone growth and remodeling, and in microdeletion cases, these issues may be more pronounced, sometimes requiring orthopedic evaluation and treatment.Joint laxity and low muscle tone (hypotonia)
Loose joints and low muscle tone can make children seem “floppy” or clumsy and may delay motor milestones. Joint laxity has been reported more often in type-1 NF1 microdeletion patients, possibly due to loss of nearby genes involved in connective tissue structure.Congenital heart defects and vascular problems
Some patients have congenital heart defects or blood vessel abnormalities. These may include narrowed arteries, aneurysms, or structural heart problems. Such cardiovascular issues require screening and regular follow-up because they can influence long-term health.Higher risk of malignant peripheral nerve sheath tumors (MPNST)
NF1 microdeletion syndrome carries an especially high risk for MPNST, a type of aggressive cancer that can arise in plexiform neurofibromas. Because of this, guidelines now recognize NF1 microdeletion as a specific risk factor and recommend early imaging and careful monitoring for worrisome changes in pain, size, or consistency of tumors.Emotional and social impact
Chronic visible skin tumors, learning problems, and medical visits can cause low self-esteem, social isolation, and stress for patients and families. Even though this is not a direct biological symptom, it is an important part of the syndrome and needs supportive care and counseling.
Diagnostic tests
In real life, doctors do not need all 20 tests for every person. They choose tests based on symptoms. Here we list 20 useful tests and explain them in simple language, grouped by category.
Physical exam tests
General physical and dysmorphology examination
The doctor looks closely at the child’s overall body shape, facial features, and posture. They check for signs such as wide-set eyes, large head, tall stature, or unusual body proportions that are common in NF1 microdeletion syndrome. This careful visual exam helps suggest the diagnosis and guides which further tests are needed.Detailed skin examination
The doctor examines the entire skin surface, often with good lighting and sometimes a small magnifying tool. They count café-au-lait spots, look for axillary or groin freckling, and feel for cutaneous and subcutaneous neurofibromas. In NF1 microdeletion syndrome, many neurofibromas and early onset lesions raise suspicion of a microdeletion.Growth and body proportion measurements
Height, weight, and head circumference are measured and plotted on growth charts. The doctor also looks at hand and foot size and body proportions. Children with NF1 microdeletion syndrome often show tall stature, macrocephaly, and large extremities, so these simple measurements help differentiate the syndrome from classic NF1.Blood pressure and cardiovascular exam
Blood pressure is measured regularly because NF1 can cause high blood pressure, especially if there are blood vessel changes or kidney artery narrowing. The doctor also listens to the heart, checks pulses, and looks for signs of heart defects or vascular problems, which may be more common in some NF1 microdeletion patients.
Manual (clinical) tests
Developmental milestone assessment
The doctor or developmental specialist asks about and observes how the child sits, walks, speaks, and plays. They compare these skills to typical age expectations. Children with NF1 microdeletion syndrome often show delays in walking, talking, or fine hand skills, so this simple, hands-on assessment is very important.Cognitive and learning evaluation
Psychologists use age-appropriate tests, school reports, and interviews to evaluate learning, attention, and memory. This may include IQ testing and specific tests for reading, writing, or math. Many NF1 microdeletion patients need this evaluation to plan special education and therapy.Motor and balance testing
The examiner may ask the child to walk, run, stand on one foot, or do finger-to-nose tasks. These simple manual tests check muscle tone, coordination, and balance. Joint laxity and low muscle tone, common in NF1 microdeletion syndrome, can be picked up by these bedside assessments.Vision screening and basic eye exam
Using a Snellen chart or picture chart, the clinician checks how well the child sees at distance and near. They may also examine the eyes with a light for signs of Lisch nodules (iris spots) or optic pathway problems. While similar tests are done in all NF1 patients, microdeletion patients still need regular eye checks due to higher overall complication risk.
Lab and pathological tests
Complete blood count and basic biochemistry
A blood sample is taken to measure hemoglobin, white cells, platelets, and basic organ function. This test does not diagnose NF1 microdeletion syndrome directly but helps detect complications, such as anemia, infection, or organ problems that could be related to tumors or treatment.Hormone and endocrine tests
If the child has very rapid growth, delayed puberty, or other hormonal signs, blood tests for hormones such as thyroid, growth hormone, or cortisol may be done. NF1 and its microdeletion form can affect the hypothalamus and pituitary region, so hormone testing helps explain unusual growth or puberty patterns.Chromosomal microarray (CMA)
CMA is a key test for NF1 microdeletion syndrome. It scans the whole genome to detect small deletions and duplications, including the 17q11.2 region. When the microarray shows a deletion that includes NF1, this confirms the presence of a microdeletion and helps classify its type and size.NF1 gene–specific testing (MLPA or NGS)
Multiplex ligation-dependent probe amplification (MLPA) and next-generation sequencing (NGS) are used to examine the NF1 gene region in detail. MLPA is especially good at detecting large deletions and duplications, while NGS finds smaller changes. Together with CMA, these tests distinguish microdeletion cases from patients who have only small NF1 variants.Tumor biopsy and histopathology
If a tumor grows quickly, becomes very painful, or feels hard, doctors may remove a part of it for microscopic examination. The pathologist checks whether it is a benign neurofibroma or a malignant peripheral nerve sheath tumor. Because NF1 microdeletion syndrome carries higher MPNST risk, biopsy is important when features suggest cancer.Prenatal genetic testing (CVS or amniocentesis with microarray)
If one parent is known to have NF1 microdeletion syndrome, or a previous child is affected, prenatal testing can be offered. Chorionic villus sampling or amniocentesis collects fetal cells, and chromosomal microarray then checks for the 17q11.2 deletion. This test helps families plan and make informed decisions.
Electrodiagnostic tests
Electroencephalogram (EEG)
An EEG records electrical activity of the brain using small electrodes on the scalp. It is used when there are seizures, staring spells, or unusual movements. In NF1 microdeletion syndrome, an abnormal EEG pattern can confirm that seizures are present and helps guide anti-seizure treatment.Nerve conduction studies and electromyography (EMG)
These tests measure how well nerves carry signals and how muscles respond. Small electrical pulses and needles are used in a controlled way. They are done if there is weakness, numbness, or signs of peripheral nerve problems. They help show how neurofibromas or other NF1-related changes are affecting nerve function.
Imaging tests
Brain MRI
Magnetic resonance imaging (MRI) of the brain is a key test. It can show optic pathway gliomas, other brain tumors, white matter signal changes, or structural malformations. In NF1 microdeletion syndrome, MRI is also used to screen for tumors and complications early, especially because tumor risk is higher than in typical NF1.Spine MRI
MRI of the spine looks for spinal neurofibromas, intramedullary lesions, and bony changes. These findings can explain back pain, weakness, or sensory problems. Because microdeletion patients may have more extensive tumor load, spine MRI is part of thorough staging and follow-up.Whole-body MRI (WBMRI)
Whole-body MRI is increasingly used in NF1 to assess the total number and size of plexiform neurofibromas and other tumors throughout the body. In NF1 microdeletion syndrome, where tumor burden and malignancy risk are higher, WBMRI helps in early detection, risk stratification, and planning of surveillance and treatment.Echocardiography and vascular imaging
Echocardiography is an ultrasound scan of the heart, and other imaging like CT or MRI angiography can show blood vessels. These tests are used if a heart murmur, high blood pressure, or other signs suggest heart or vessel problems. NF1 patients, including those with microdeletions, can have congenital heart defects and vascular abnormalities, so these tests are important for full evaluation.
Non-Pharmacological Treatments
1. Regular multidisciplinary NF clinic follow-up
Being seen at an NF clinic with genetics, neurology, dermatology, ophthalmology, orthopaedics and psychology allows early detection of tumours, scoliosis, vision loss and learning issues, which is especially important in NF1 microdeletion syndrome.3
2. Structured tumour surveillance and imaging
Scheduled MRI or targeted imaging of plexiform neurofibromas and the brain/spine, guided by symptoms and guidelines, helps detect tumour growth and possible malignant change sooner, improving treatment options and outcomes.4
3. Genetic counselling for family planning
Genetic counselling explains inheritance (usually autosomal dominant with 50% recurrence risk), options such as prenatal or pre-implantation testing, and supports family decision-making in a sensitive, informed way.1
4. Early developmental and educational support
Children with NF1 microdeletion syndrome often have developmental delay or learning difficulties, so early intervention, special education plans, tutoring and classroom accommodations can improve school performance and independence.2
5. Neuropsychological assessment and cognitive training
Formal testing of attention, memory and executive function identifies ADHD, autism traits or specific learning disorders, allowing tailored cognitive training, behavioural strategies and school support.5
6. Behavioural therapy for ADHD and emotional issues
Cognitive-behavioural therapy (CBT), parent training and behavioural school programs help manage inattention, hyperactivity, anxiety, low mood and social difficulties that are common in NF1 microdeletion syndrome.5
7. Physiotherapy and exercise programs
Physiotherapy, tailored exercise, balance and strength training address clumsiness, muscle weakness and reduced fitness, and can improve bone density, posture and pain control.6
8. Occupational therapy (OT)
OT helps with fine motor skills, handwriting, daily living tasks, and environmental adaptations at home and school (special seating, keyboarding, sensory tools), supporting independence and participation.6
9. Speech and language therapy
Some children have language delay or social communication difficulties; speech therapy can improve understanding, expression, articulation and social communication, which enhances learning and friendships.2
10. Psychological counselling for patients and families
Living with a tumour-predisposition syndrome is stressful. Individual or family counselling offers coping strategies for anxiety about tumours, body image, chronic pain and future risks.5
11. Pain management with non-drug techniques
Physical therapy, heat/cold, relaxation, mindfulness, CBT for pain and pacing of activities may reduce chronic pain from plexiform neurofibromas or skeletal problems and limit reliance on long-term pain medicines.6
12. Vision and low-vision rehabilitation
If optic pathway gliomas or other eye issues reduce vision, low-vision aids, orientation training and classroom adaptations can help maintain school and daily functioning.3
13. Orthopaedic bracing and physiotherapy for scoliosis
Braces, targeted exercises and careful monitoring can slow progression of scoliosis or limb deformity, sometimes delaying or reducing the need for major spinal surgery.3
14. Sleep hygiene and treatment of sleep problems
Fixed sleep schedules, good sleep habits, and treatment of sleep apnoea or restless legs (when present) improve daytime concentration, mood and overall quality of life.5
15. Healthy lifestyle and regular physical activity
Because NF1 is linked with reduced bone density and sometimes cardiovascular risk, a healthy weight, regular weight-bearing exercise and not smoking support bone, heart and overall health.7
16. Social work support and patient organisations
Social workers and NF advocacy groups help families access financial assistance, school accommodations, employment support and community resources, reducing stress and isolation.5
17. Vocational counselling in adolescence and adulthood
Career counselling that considers learning style, physical limitations and tumour burden can guide realistic and satisfying job choices for adults with NF1 microdeletion syndrome.5
18. Pregnancy and reproductive counselling
High-risk obstetric and genetics teams help plan safe pregnancies, discuss inheritance risk, and monitor for hypertension or tumour-related complications during pregnancy.3
19. Telemedicine and remote monitoring
Virtual NF visits and remote symptom reporting can improve access to experts for people living far from NF centres while maintaining regular surveillance and treatment planning.4
20. Education about red-flag symptoms
Teaching families to watch for rapid tumour growth, new pain, weakness, vision changes, seizures or weight loss helps them seek urgent care quickly, which is crucial in a high-risk microdeletion phenotype.4
Drug Treatments
Important: Drug choices and doses must always be made by specialists based on age, tumour burden and other health problems. Information below is general and based on FDA labels and NF1 guidelines, not personal medical advice.
1. Selumetinib (KOSELUGO) – MEK inhibitor
Selumetinib is an oral MEK1/2 inhibitor approved for children ≥1 year with NF1 and symptomatic, inoperable plexiform neurofibromas, and more recently for adults, reducing tumour volume and pain in many patients. Dosing is weight-based, twice daily, with common side effects including gastrointestinal upset, skin rash and cardiac or ocular toxicity, so careful monitoring is essential.6
2. Mirdametinib (GOMEKLI) – MEK inhibitor
Mirdametinib is another oral MEK1/2 inhibitor approved for adults and children ≥2 years with NF1 and symptomatic plexiform neurofibromas not amenable to complete resection. It is taken orally in cycles, and can shrink tumours and improve function but may cause rash, diarrhoea, heart and eye problems, requiring close specialist supervision.7
3. Everolimus – mTOR inhibitor in selected cases
Everolimus, an mTOR inhibitor, has been studied for NF1-related plexiform neurofibromas and other tumours. Some studies show limited or modest benefit, and others show no clear efficacy, so its use is generally restricted to trials or specific tumour indications, with side effects like mouth ulcers, infections and lipid abnormalities.8
4. Standard chemotherapy for malignant peripheral nerve sheath tumours (MPNST)
If NF1 microdeletion leads to malignant tumour transformation, oncologists may use multi-agent chemotherapy (for example doxorubicin plus ifosfamide), based on sarcoma protocols, with careful balancing of tumour control against risks like cardiotoxicity, infertility and infection.4
5. Antiepileptic drugs (for seizures)
When NF1-related brain lesions cause seizures, antiepileptic drugs like levetiracetam are often used because they have relatively few interactions and are well studied; dosing is individualized, and side effects can include fatigue, mood changes and behavioural symptoms.9
6. Analgesics and anti-inflammatory drugs for pain
Paracetamol (acetaminophen) and non-steroidal anti-inflammatory drugs (NSAIDs) are standard first-line medicines for mild to moderate pain from neurofibromas or orthopaedic problems; stronger drugs or neuropathic pain agents are sometimes added if pain persists.6
7. Antihypertensive drugs
NF1 can cause high blood pressure due to renal artery stenosis or pheochromocytoma. ACE inhibitors, beta-blockers or calcium-channel blockers are chosen according to cause, age and comorbidities, following general hypertension guidelines, to reduce stroke and heart disease risk.3
8. ADHD stimulant medication (e.g., methylphenidate)
Children with NF1 microdeletion often meet criteria for ADHD. Stimulant medicines like methylphenidate can improve attention and school performance but require careful dosing, monitoring for appetite and sleep problems, and awareness of updated FDA warnings on growth and weight loss in young children.10
9. Non-stimulant ADHD medications
Non-stimulant agents (such as atomoxetine or certain alpha-2 agonists) may be used when stimulants are poorly tolerated or contraindicated, helping with attention and impulsivity but potentially causing blood pressure or liver-related side effects that must be monitored.5
10. Antidepressants (SSRIs and others)
Anxiety and depression are more common in NF1. Selective serotonin reuptake inhibitors (SSRIs) and related drugs can improve mood, sleep and functioning when combined with psychotherapy, but require monitoring for activation, suicidal thoughts in youth and drug interactions.5
11. Anxiolytics and sleep medications (short-term use)
Short courses of non-benzodiazepine hypnotics or other sleep-supportive medicines may be considered when insomnia is severe and behavioural strategies are insufficient, but long-term use is generally avoided because of dependence and cognitive side effects.5
12. Bisphosphonates for osteoporosis
Because NF1 is associated with low bone mineral density and fractures, standard osteoporosis treatments such as bisphosphonates may be used in adults with fragility fractures or very low bone density, together with vitamin D and calcium supplementation.7
13. Hormonal therapies in specific tumour types
If NF1 microdeletion is associated with hormone-sensitive tumours (for example, breast cancer), oncologists may use endocrine therapies (such as tamoxifen or aromatase inhibitors) according to standard cancer guidelines rather than NF1-specific protocols.4
14. Chemotherapy for optic pathway gliomas and low-grade gliomas
When vision-threatening optic pathway gliomas appear, paediatric oncology protocols using agents like carboplatin and vincristine can stabilise or shrink tumours, aiming to preserve vision while balancing toxicity.3
15. Antihistamines and topical agents for pruritus
Some skin lesions itch or cause discomfort. Non-sedating antihistamines and emollients are used first; topical anaesthetics or other creams may be added short-term for severe local symptoms.6
16. Proton-pump inhibitors and supportive GI medicines
MEK inhibitors and other systemic treatments can irritate the stomach or cause reflux; proton-pump inhibitors or antiemetics may be prescribed to improve tolerability and allow patients to continue life-saving therapies when appropriate.6
17. Topical or procedural dermatologic treatments
Though not classic “drugs”, topical treatments and procedures like laser ablation or electrodessication for small cutaneous neurofibromas may be combined with local anaesthetics and antiseptics to improve cosmesis and comfort.6
18. Vaccinations and infection prophylaxis
Routine vaccines (influenza, pneumococcal, COVID-19 and others according to national schedules) are important in people who may need surgery, chemotherapy or long-term targeted therapy, reducing infection-related complications.3
19. Cardiovascular risk-reduction medications
If NF1 patients develop dyslipidaemia or diabetes, statins or glucose-lowering agents are used as in the general population to reduce cardiovascular risk, which is important because NF1 is linked with reduced life expectancy.11
20. Supportive medicines around surgery and anaesthesia
Analgesics, antiemetics, antibiotics and thrombosis prophylaxis are used around NF1-related operations following standard surgical protocols, tailored to tumour location, extent of surgery and patient comorbidities.3
Dietary Molecular Supplements
Important: No supplement has been proven to “cure” NF1 microdeletion syndrome. Supplements should be guided by doctors and dietitians, checking for deficiencies and interactions.
1. Vitamin D3 (cholecalciferol)
NF1 patients often have low vitamin D levels and reduced bone mineral density; vitamin D3 supplementation, at doses chosen by doctors, can improve bone density and may relate to fewer or less severe neurofibromas, though evidence is still emerging.8
2. Calcium
Adequate dietary calcium or supplements (if intake is low) support bone mineralisation, especially when paired with vitamin D and physical activity, helping counteract the osteoporosis commonly reported in NF1.7
3. L-carnitine
A small trial in children with NF1 suggests that L-carnitine supplementation may improve muscle performance and intramuscular lipid metabolism; dosing should follow research protocols or specialist advice, as long-term safety data are limited.12
4. Omega-3 fatty acids
Omega-3 fatty acids from fish oil or diet (fatty fish) may support cardiovascular health and reduce inflammation; although not NF1-specific, they can be reasonable in patients with high cardiovascular risk and poor diet quality.9
5. Multivitamin with B vitamins
Some studies suggest altered B12 and other vitamin status in NF1, and a general multivitamin can correct mild deficiencies, but should not replace a balanced diet and should be tailored to blood test results.13
6. Magnesium and trace minerals
Dietary studies show many NF1 patients consume inadequate magnesium and other minerals, which are important for bone and muscle function; low-dose supplements under dietetic guidance may be helpful when intake is clearly insufficient.9
7. Medium-chain triglycerides (MCTs)
Research suggests diets including medium-chain fatty acids may support muscle metabolism and lipolysis in NF1 models; MCT-enriched foods or supplements should still be balanced within an overall healthy eating pattern.14
8. Antioxidant-rich foods or supplements
Because NF1 is a tumour-predisposition condition, antioxidants from fruits, vegetables and possibly low-dose supplements may support general cellular health, though no supplement has proven anti-tumour benefit in NF1.14
9. Protein-rich nutrition support
Adequate protein intake from food or supplements is important for healing after surgery, maintaining muscle mass and supporting growth in children with NF1 microdeletion syndrome, who may have higher metabolic demands.6
10. Individualised dietitian-guided supplementation plans
Because diet quality is often poor in NF1, best practice is to have a registered dietitian design a personalised plan that may include specific micronutrients, rather than using many random over-the-counter products.9
Immunity Booster, Regenerative and Stem-Cell-Related Drugs
There are no approved stem-cell or true “regenerative” drugs specifically for NF1 microdeletion syndrome. The points below explain real, evidence-based areas rather than unproven “miracle” cures.
1. Optimised vitamin D3 and calcium
Correcting vitamin D deficiency and ensuring enough calcium supports bone “regeneration”, improves bone density and may have positive immune and skin effects, but it does not reverse the NF1 microdeletion.8
2. MEK inhibitors as “tumour-modifying” targeted therapy
Selumetinib and mirdametinib do not boost immunity or regenerate nerves, but they can shrink plexiform neurofibromas by targeting abnormal RAS-MAPK signalling, which is a disease-modifying effect at the tumour level.6
3. Experimental mTOR inhibition (everolimus)
Everolimus has been tested as an antiproliferative agent in NF1 tumours with mixed results; it is not standard care but shows how signalling-pathway drugs may partly “remodel” tumour behaviour in some patients under research protocols.8
4. Haematopoietic stem-cell transplantation (for associated malignancies)
If NF1 microdeletion is complicated by blood cancers that need bone-marrow transplant, standard haematopoietic stem-cell transplantation is used, but this treats the malignancy, not the underlying NF1 gene deletion.4
5. Growth and endocrine therapies
In selected children with proven growth hormone deficiency or other endocrine disorders, hormone replacement may support better growth and bone health, but must be carefully balanced against theoretical tumour-growth risks.3
6. Clinical trials of novel biologics or cell-based therapies
Any future “regenerative” or cell-based approaches for NF1 microdeletion syndrome should only be accessed within ethically approved clinical trials at recognised centres, never via unregulated clinics or internet advertising.4
Surgical Treatments
1. Excision of disfiguring or painful cutaneous neurofibromas
Individual cutaneous neurofibromas can be surgically removed or treated with dermatologic procedures when they cause pain, irritation or major cosmetic distress, though new lesions can still appear over time.6
2. Debulking of plexiform neurofibromas
Large plexiform neurofibromas compressing nerves, airways or organs may be partially removed to relieve symptoms. Complete removal is often impossible, and surgery must be balanced against bleeding, nerve damage and regrowth risk.4
3. Orthopaedic surgery for skeletal deformities
Procedures such as spinal fusion for severe scoliosis, fixation of tibial pseudarthrosis or correction of limb deformities can improve mobility, reduce pain and prevent long-term disability in NF1 microdeletion patients.3
4. Neurosurgical decompression
If tumours compress the spinal cord or peripheral nerves causing weakness, numbness or bladder problems, neurosurgical decompression may prevent permanent neurological damage, although surgery can be complex and risky.3
5. Surgery for associated tumours (e.g., MPNST, pheochromocytoma)
When malignant peripheral nerve sheath tumours, pheochromocytomas or other solid tumours arise, surgical resection with clear margins is often central to treatment, combined with oncology care as needed.4
Preventions
NF1 microdeletion syndrome itself cannot be prevented because it is genetic, but many complications can be reduced or detected early.
1. Regular NF1 specialist follow-up with full examinations, blood pressure checks and age-appropriate imaging.3
2. Prompt reporting of new or rapidly growing lumps, pain, weakness or weight loss to allow early evaluation for malignant transformation.4
3. Routine eye examinations in childhood to detect optic pathway gliomas before severe vision loss.3
4. Annual blood pressure measurement to prevent untreated hypertension and stroke.3
5. Bone health measures such as vitamin D, calcium, weight-bearing exercise and avoiding smoking to reduce fractures.7
6. Vaccinations and infection prevention, especially before major surgery or immunosuppressive treatments.3
7. Healthy diet and weight control to limit cardiovascular risk and support bone and muscle health.9
8. Avoidance of unnecessary radiation exposure (for example, limiting repeated CT scans) because NF1 increases tumour risk.4
9. Genetic counselling before pregnancy so families understand recurrence risk and prenatal testing options.1
10. Mental-health support and early treatment of anxiety/depression to reduce self-harm risk and improve adherence to medical care.5
When to See Doctors
People with NF1 microdeletion syndrome should have regular planned visits with an NF specialist at least once a year, more often in childhood or during active tumour treatment. Urgent medical review is needed if there is rapid growth of any lump, persistent or new severe pain, unexplained weight loss, new weakness or numbness, changes in walking, bladder or bowel control, sudden vision or hearing changes, new seizures, very high blood pressure, or repeated vomiting and headaches, as these can signal serious tumour or neurological complications.3
Diet: What to Eat and What to Avoid
1. Emphasise whole, minimally processed foods
NF1 diet studies show many patients eat too much fat and sodium and too few vitamins and minerals, so focusing on vegetables, fruits, whole grains and legumes helps correct this imbalance.9
2. Include vitamin-D-rich foods
Oily fish, fortified dairy or plant milks and eggs provide vitamin D and work together with supplements and sunlight exposure to improve bone health in NF1.8
3. Ensure adequate calcium intake
Low-fat dairy products, calcium-set tofu, leafy greens and fortified foods support bone mineralisation and should be included daily unless contraindicated.7
4. Choose healthy fats
Use olive or canola oil and nuts instead of saturated fats; medium-chain triglyceride sources may have additional benefits for muscle metabolism in some NF1 patients.14
5. Prioritise lean proteins
Lean meats, fish, eggs, beans and lentils support growth, wound healing and muscle strength, which are all important in a condition associated with surgeries and reduced physical activity.6
6. Limit processed meats and high-fat fast foods
These foods add saturated fat, salt and calories without needed nutrients and have been over-consumed in NF1 cohorts, contributing to cardiovascular risk.9
7. Reduce sugary drinks and sweets
Limiting sugary drinks and sweets helps prevent obesity and metabolic syndrome, which can complicate tumour treatment and bone health.9
8. Avoid very high-sodium snack foods
Chips, instant noodles and salty snacks add excess sodium, which is already high in NF1 diets and may worsen hypertension risk.9
9. Be cautious with unproven supplements
Herbal “tumour-shrinking” pills or internet “immunity boosters” lack evidence and may interact with MEK inhibitors or chemotherapy, so they should be avoided unless approved by the treating team.14
10. Work with a dietitian for an individual plan
Because each person’s weight, activity level, tumour burden and treatments are different, a registered dietitian can create a safe, enjoyable and realistic eating plan tailored to that person.9
Frequently Asked Questions
1. How is NF1 microdeletion syndrome different from “classic” NF1?
NF1 microdeletion syndrome involves loss of the NF1 gene plus neighbouring genes, leading to more severe symptoms: more neurofibromas, earlier onset tumours, greater learning difficulties and higher risk of complications than typical single-gene NF1 variants.1
2. Is NF1 microdeletion syndrome inherited?
Many cases arise “de novo” (new in the child), but once a person has the microdeletion, there is about a 50% chance of passing it to each child, so genetic counselling is recommended.1
3. Can NF1 microdeletion syndrome be cured?
There is currently no cure that replaces the missing DNA. Treatment focuses on lifelong surveillance, early diagnosis of complications, and use of targeted therapies (like MEK inhibitors) and surgery to control tumours and symptoms.4
4. What is the life expectancy?
NF1 overall is associated with a reduced life expectancy, mainly due to malignant tumours and vascular problems; people with microdeletion may have higher risk and therefore benefit especially from early, aggressive surveillance and treatment.11
5. Do all people with NF1 microdeletion syndrome develop cancer?
No. Cancer risk is higher than in the general population, but not everyone develops cancer. Regular monitoring is designed to catch suspicious changes early, when treatment works best.4
6. Can lifestyle changes really help?
Lifestyle cannot change the gene deletion, but good diet, exercise, bone health, avoiding smoking and attending all NF clinic appointments can reduce complications and improve quality and length of life.7
7. Are MEK inhibitors suitable for everyone with NF1 microdeletion?
MEK inhibitors such as selumetinib and mirdametinib are approved only for patients with symptomatic, inoperable plexiform neurofibromas and have important side effects, so they are used when benefits clearly outweigh risks.6
8. At what age should monitoring start?
Monitoring typically begins in infancy or early childhood, with skin and eye exams, developmental checks and, later, blood pressure and imaging guided by symptoms and guidelines.3
9. Can children with NF1 microdeletion attend mainstream school?
Many can, but they often need additional educational support, accommodations and sometimes special schooling. Early neuropsychological assessment helps schools provide the right help.2
10. Is pregnancy safe in NF1 microdeletion syndrome?
Many people with NF1 have successful pregnancies, but there may be higher risk of hypertension, tumour growth and obstetric complications; pre-pregnancy counselling and high-risk obstetric care are recommended.3
11. Do diet and supplements change tumour risk?
Current evidence suggests vitamin D and a healthy diet support bone and general health but do not replace medical surveillance or tumour-directed treatment. No supplement has proven anti-tumour efficacy in NF1.8
12. Should people with NF1 microdeletion avoid sports?
Most people can participate in physical activity and non-contact sports, which improve bone and cardiovascular health. Contact sports may need caution if there are large tumours or skeletal fragility; decisions are individual.7
13. How often are scans needed?
There is no single schedule; imaging (MRI) is recommended when symptoms appear or when specific tumours need monitoring. Some high-risk patients may follow structured tumour-surveillance protocols in expert centres.4
14. Are “stem-cell clinics” advertised online safe for NF1?
Unregulated stem-cell therapies marketed online are not recommended; they lack evidence, can cause harm and may delay proven treatments. Any advanced therapy should be accessed only in approved clinical trials.4
15. What is the most important message for families?
NF1 microdeletion syndrome is serious but manageable. The most important steps are: staying connected to an experienced NF team, attending regular check-ups, reporting red-flag symptoms early, supporting learning and mental health, and following evidence-based treatments rather than unproven cures.5
Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.
The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members
Last Updated: January 16, 2026.
