Materiały źródłowe

• #1 Pathology Outlines – Neurofibroma-general

  https://www.pathologyoutlines.com/topic/softtissueneurofibroma.html

  Neurofibroma is a benign peripheral nerve sheath tumor comprised of neuronal and fibrous components. […] It is composed of Schwann cells, perineurial cells, fibroblasts, mast cells and interspersed myelinated and unmyelinated axons within a myxoid and collagenous extracellular matrix. […] Diagnosis includes physical examination, biopsy of lesion demonstrating classic histologic features, and imaging techniques such as MRI or PET/CT based on the size and location of the lesion. […] 18F-FDG PET/CT is used to differentiate between benign and malignant tumors in neurofibroma patients.

• #1 Neurofibromatosis type 1 – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/neurofibromatosis-type-1/diagnosis-treatment/drc-20350495

  To diagnose neurofibromatosis type 1 (NF1), a healthcare professional begins with a review of your personal and family medical history and a physical exam. […] Your child’s skin is checked for cafe au lait spots, which can help diagnose NF1. […] If other tests are needed to diagnose NF1, your child may need: Eye exam. An eye exam can reveal Lisch nodules, cataracts and vision loss. […] Imaging tests. X-rays, CT scans or MRIs can help identify bone changes, tumors in the brain or spinal cord, and very small tumors. An MRI might be used to diagnose optic gliomas. […] Genetic tests. Genetic testing for NF1 can help support the diagnosis. Genetic tests also can be done in pregnancy before a baby is born. Ask a member of your healthcare team about genetic counseling. […] For a diagnosis of NF1, at least two symptoms of the condition must be present. A child who has only one symptom and no family history of NF1 is likely to be monitored for any other symptoms. A diagnosis of NF1 is usually made by age 4.

• #2 Neurofibroma: Definition, Types & Treatment

  https://my.clevelandclinic.org/health/diseases/22535-neurofibroma

  Healthcare providers typically use a physical examination to diagnose neurofibromas. […] They might also use the following imaging tests: […] Healthcare providers use these tests to find very small tumors. […] Healthcare providers use this test to see if a tumor is benign (noncancerous) or cancerous (malignant). […] If your neurofibroma is benign (noncancerous) and isnt causing problems, your healthcare provider may recommend regular check-ups to monitor for changes. […] Your healthcare provider may recommend removing benign tumors that are on the surface of your skin or beneath your skin. […] If you have neurofibromas pressing on your bones or organs, your healthcare provider may recommend surgery to remove as many tumors or as much of a tumor as possible without damaging your organs and tissues.

• #3 Neurofibroma | Radiology Reference Article | Radiopaedia.org

  https://radiopaedia.org/articles/neurofibroma?lang=us

  The clinical presentation of localized intraneural neurofibromas is non-specific and the result of either mass effect on surrounding lesions (or palpable lump) or neurogenic dysfunction. […] They are considered WHO grade 1 tumors in the 5th edition (2021) WHO classification of CNS tumors. […] Localized intraneural neurofibromas are composed of Schwann cells and fibroblasts, containing a rich network of collagen fibers. […] For lesions not associated with neurofibromatosis type 1: localized and diffuse lesions may be treated surgically; however, as neurofibromas infiltrate between nerve fascicles, they are unable to be separated from the parent nerve and complete excision requires the sacrifice of the nerve. […] For lesions associated with neurofibromatosis type 1: due to the multiplicity of lesions, unless debilitating symptoms are present, treatment of patients with neurofibromatosis type 1 is often non-surgical. […] Malignant change of sporadic localized intraneural neurofibromas is most frequently seen in large neurofibromas, and even then it only occurs in 5-10% of tumors.

• #4 Neurofibroma differential diagnosis – wikidoc

  https://www.wikidoc.org/index.php/Neurofibroma_differential_diagnosis

  Neurofibroma can be sporadic or as a part of Neurofibromatosis 1 and 2. […] Neurofibroma with degenerative atypia („ancient change”) has following microscopic features: Localized cells with large pleomorphic nuclei, cytoplasmic nuclear inclusions, smudgy chromatin, and inconspicuous nuclei. […] Positive for: S100 (weaker), SOX10, Neurofilament (and Bielshowsky), GFAP, CD34 (stronger), Factor XIIIa, Calretinin (focal), MBP (myelin-basic protein). […] Negative for: EMA (except in plexiform neurofibromas). […] Neurofibromatosis 1, Neurofibromatosis 2 (multiple neurofibromas, meningiomas of the brain or spinal cord, and ependymomas of the spinal cord). […] Can occur anywhere. […] Diffuse neurofibromas commonly involve scalp. […] Soft masses/bumps on or under skin (internal or superficial), Transient itching (mast cells release histamine), Transient pain, Numbness and tingling in the affected area, Severe bleeding (sign of tumor growth), Physical disfiguration, Cognitive disability, Stinging, Neurological deficits, Changes in movement (clumsiness in hands, trouble walking), Bowel incontinence, Scoliosis (an abnormal curvature of the spine, if the tumor creates muscular imbalance or erodes bones of the spine).

• #5 Guidelines for the diagnosis and management of individuals with neurofibromatosis 1 | Journal of Medical Genetics

  https://jmg.bmj.com/content/44/2/81

  Neurofibromatosis 1 (NF1) is a common neurocutaneous condition with an autosomal dominant pattern of inheritance. […] Members of the United Kingdom Neurofibromatosis Association Clinical Advisory Board collaborated to produce a consensus statement on the current guidelines for diagnosis and management of NF1. […] The National Institutes of Health Consensus Development Conference formulated the diagnostic criteria for neurofibromatosis 1 (NF1), underlining the pivotal involvement of the skin, bone and the nervous system in the condition. […] NF1 has a birth incidence of 1 in 2500 to 1 in 3000, the diagnosis is based on clinical assessment and two or more of the features in table 1 are required. […] These diagnostic criteria are robust and have stood the test of time well. […] NF1 mutational analysis clarifies the diagnosis in some uncertain cases and in individuals contemplating prenatal diagnosis.

• #6 Neurofibromatosis Type 1: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1177266-overview

  Neurofibromatosis type 1 (NF1) is a multisystem genetic disorder that is characterized by cutaneous findings, most notably caf-au-lait spots and axillary freckling, by skeletal dysplasias, and by the growth of both benign and malignant nervous system tumors, most notably benign neurofibromas. […] An international consensus revised the diagnostic criteria for NF1 in 2021. In the absence of a parent with NF1, the criteria for clinical diagnosis includes two or more of the following: Six or more caf-au-lait (CAL) macules greater than 5 mm in diameter in prepubertal children and greater than 15 mm postpubertal; Axillary or inguinal freckles (2 freckles) (if only CAL and freckling are present, one of these two cutaneous manifestations should be bilateral, and Legius syndrome should be considered, though the diagnosis is still likely NF1); Two or more typical neurofibromas or one plexiform neurofibroma; Optic pathway glioma; Two or more iris hamartomas (Lisch nodules), often identified only through slit-lamp examination by an ophthalmologist; or two or more choroidal abnormalities; Sphenoid dysplasia or typical long-bone abnormalities such as pseudarthrosis; Heterozygous pathogenic NF1 variant with a variant allele fraction of 50% in apparently normal tissue. […] In the presence of a parent with NF1, the criteria for clinical diagnosis include one of the above criteria.

• #7 Neurofibromatosis type I – Wikipedia

  https://en.wikipedia.org/wiki/Neurofibromatosis_type_I

  Prenatal testing may be used to identify the existence of NF-1 in the fetus. […] While the presence of NF-1 can be identified through prenatal testing the severity with which the condition will be expressed is impossible to determine. […] The National Institutes of Health (NIH) has created specific criteria for the diagnosis of NF-1. Two of these seven „Cardinal Clinical Features” are required for positive diagnosis. […] Six or more caf-au-lait spots over 5 mm in greatest diameter in pre-pubertal individuals and over 15 mm in greatest diameter in post-pubertal individuals. […] Two or more neurofibromas of any type or 1 plexiform neurofibroma. […] Freckling in the axillary (Crowe sign) or inguinal regions. […] Optic nerve glioma. […] Two or more Lisch nodules (pigmented iris hamartomas). […] A distinctive osseous lesion such as sphenoid dysplasia, or thinning of the long bone cortex with or without pseudarthrosis. […] A first degree relative (parent, sibling, or offspring) with NF-1 by the above criteria.

• #8 Table: Diagnosing Neurofibromatosis-Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/multimedia/table/diagnosing-neurofibromatosis

  Diagnosing Neurofibromatosis […] If the patient has a parent diagnosed with NF1 and meets at least 1 of the criteria below, the diagnosis of NF1 is made. […] If the patient does not have a parent diagnosed with NF1, 2 of the following must be present: […] 2 neurofibromas of any type or 1 plexiform neurofibroma. […] NF2-related schwannomatosis (NF2) 1 of the following: […] An identical NF2 pathogenic variant in at least 2 anatomically distinct NF2-related tumors (schwannoma, meningioma, and/or ependymoma). […] Major criteria (2 of the following): […] NF2 pathogenic variant in an unaffected tissue (eg, blood). […] One major criterion and 2 of the following minor criteria: […] Pattern of genetic changes in unaffected tissue and in tumor tissue in NF2. […] Non-NF2 schwannomatosis (schwannomatosis) SMARCB1- and LZTR1-related schwannomatosis (1 of the following):

• #9 Neurofibroma Diagnosis & Treatment – NYC | Columbia Neurosurgery in New York City

  https://www.neurosurgery.columbia.edu/patient-care/conditions/neurofibroma

  Neurofibromas can be identified on MR (magnetic resonance) and CT (computed tomography) scans. […] On these scans, neurofibromas resemble schwannomas, another type of nerve tumor. […] These tumor types may be impossible to distinguish on imaging and often require tissue biopsy for pathologic evaluation in the laboratory. […] Neurofibromas are the more difficult type of tumor to remove because they are more intimately involved with the nerve fibers. […] However, with meticulous surgical technique, most can be removed safely.

• #10 Pathology Outlines – Neurofibroma-general

  https://www.pathologyoutlines.com/topic/softtissueneurofibroma.html

  Neurofibroma is a benign peripheral nerve sheath tumor comprised of neuronal and fibrous components. […] It is composed of Schwann cells, perineurial cells, fibroblasts, mast cells and interspersed myelinated and unmyelinated axons within a myxoid and collagenous extracellular matrix. […] Diagnosis includes physical examination, biopsy of lesion demonstrating classic histologic features, and imaging techniques such as MRI or PET/CT based on the size and location of the lesion. […] 18F-FDG PET/CT is used to differentiate between benign and malignant tumors in neurofibroma patients.

• #11 Neurofibromatosis Type 1 Workup: Laboratory Studies, Imaging Studies, Other Tests

  https://emedicine.medscape.com/article/1177266-workup

  For a parent with NF1 who is the only affected family member, gene sequencing can be used to identify a specific gene mutation. Identification of the mutation in the affected parent would permit prenatal diagnosis via amniocentesis or chorionic villus sample (CVS). […] MRI is the preferred diagnostic head imaging study in NF1. […] MRI has been shown to frequently detect unidentified bright objects (UBOs) in the brain parenchyma of patients with NF1. […] MRI is also a valuable tool in evaluating the optic nerves or optic chiasm. […] Brain MRI should be considered in patients with headaches that are changing in quality or are increasing in frequency or intensity. […] MRI has proven useful in evaluating internal lesions such as mediastinal masses, spinal cord tumors, deep plexiform neurofibromas, neurofibromas of the brachial or sacral plexus, and abdominopelvic lesions.

• #12 Neurofibroma Symptoms and Treatment | UPMC

  https://www.upmc.com/services/neurosurgery/spine/conditions/tumors-lesions/neurofibroma

  Neurofibromas are benign tumors that grow on nerves in the body. […] Neurofibromas are benign tumors of the peripheral nerves. […] Neurofibroma Diagnosis. […] The doctor will perform a physical exam and ask about any symptoms. Symptoms depend on the size and location of the tumor. […] Neurofibromas have a characteristic appearance on MRI scans. A biopsy of the tumor taken during surgery enables a positive diagnosis.

• #13

• #14 Pathology Outlines – Neurofibroma-general

  https://www.pathologyoutlines.com/topic/softtissueneurofibroma.html

  Neurofibroma is a benign peripheral nerve sheath tumor comprised of neuronal and fibrous components. […] It is composed of Schwann cells, perineurial cells, fibroblasts, mast cells and interspersed myelinated and unmyelinated axons within a myxoid and collagenous extracellular matrix. […] Diagnosis includes physical examination, biopsy of lesion demonstrating classic histologic features, and imaging techniques such as MRI or PET/CT based on the size and location of the lesion. […] 18F-FDG PET/CT is used to differentiate between benign and malignant tumors in neurofibroma patients.

• #15 Neurofibromatosis Type 1 Workup: Laboratory Studies, Imaging Studies, Other Tests

  https://emedicine.medscape.com/article/1177266-workup

  MRI is not always helpful in differentiating benign peripheral nerve lesions from malignant lesions, central hypointense areas within a lesion noted on T2-weighted images (the so-called target sign) is more suggestive of a benign lesion. […] CT and MRI are first-line imaging studies when pheochromocytoma is suspected based on abnormal serum or urine screening tests.

• #16 Guidelines for the diagnosis and management of individuals with neurofibromatosis 1 | Journal of Medical Genetics

  https://jmg.bmj.com/content/44/2/81

  Hyperintense lesions on T2 weighted brain MRI (formerly called UBOs) are probably caused by aberrant myelination or gliosis, and are pathognomonic of NF1. […] The differential diagnoses of NF1 include other forms of neurofibromatosis, conditions with caf au lait patches or with pigment changes confused with caf au lait patches. […] The only subtype of NF1 that is distinct and has a uniform phenotype in families is Watson syndrome. […] Once the diagnosis is considered, referral should be made to any clinician skilled in the diagnosis of NF1, including geneticists, paediatricians, neurologists or dermatologists. […] The mainstay of management is age specific monitoring of disease manifestations and patient education. […] Adults with severe disease have usually been identified by this stage and require lifelong monitoring in an NF1 clinic.

• #17 Neurofibromatosis Type 1 Workup: Laboratory Studies, Imaging Studies, Other Tests

  https://emedicine.medscape.com/article/1177266-workup

  For a parent with NF1 who is the only affected family member, gene sequencing can be used to identify a specific gene mutation. Identification of the mutation in the affected parent would permit prenatal diagnosis via amniocentesis or chorionic villus sample (CVS). […] MRI is the preferred diagnostic head imaging study in NF1. […] MRI has been shown to frequently detect unidentified bright objects (UBOs) in the brain parenchyma of patients with NF1. […] MRI is also a valuable tool in evaluating the optic nerves or optic chiasm. […] Brain MRI should be considered in patients with headaches that are changing in quality or are increasing in frequency or intensity. […] MRI has proven useful in evaluating internal lesions such as mediastinal masses, spinal cord tumors, deep plexiform neurofibromas, neurofibromas of the brachial or sacral plexus, and abdominopelvic lesions.

• #18 Neurofibroma – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/dermatology/neurofibroma/

  Neurofibromas are benign tumors of the peripheral nerve sheath. Neurofibromas present as slow-growing tumors. They typically appear after puberty. They are generally asymptomatic, but may become painful, irritated, or pruritic. […] The diagnosis of a neurofibroma can usually be suspected clinically, but a skin biopsy is confirmatory. If a skin biopsy from a cutaneous neurofibroma is done, one sees a non-encapsulated tumor composed of fascicles of slender, spindle-shaped cells. […] Having a single plexiform neurofibroma fulfills one of the seven NIH diagnostic criteria for NF1. […] The differential diagnosis for a cutaneous neurofibroma includes: (1) dermal melanocytic nevus; (2) neuroma; (3) lipoma; (4) fibroma and (5) acrochordon. Biopsy can usually differentiate these conditions from neurofibromas. […] Patients with a solitary neurofibroma can be reassured that this is a benign lesion without risk of malignant transformation. […] Plexiform neurofibromas have a risk for malignant transformation and the patient should be monitored for rapid growth or unrelenting pain.

• #19

• #20 Pathology Outlines – Neurofibroma-general

  https://www.pathologyoutlines.com/topic/softtissueneurofibroma.html

  Neurofibroma is a benign peripheral nerve sheath tumor comprised of neuronal and fibrous components. […] It is composed of Schwann cells, perineurial cells, fibroblasts, mast cells and interspersed myelinated and unmyelinated axons within a myxoid and collagenous extracellular matrix. […] Diagnosis includes physical examination, biopsy of lesion demonstrating classic histologic features, and imaging techniques such as MRI or PET/CT based on the size and location of the lesion. […] 18F-FDG PET/CT is used to differentiate between benign and malignant tumors in neurofibroma patients.

• #21 Neurofibroma differential diagnosis – wikidoc

  https://www.wikidoc.org/index.php/Neurofibroma_differential_diagnosis

  Neurofibroma can be sporadic or as a part of Neurofibromatosis 1 and 2. […] Neurofibroma with degenerative atypia („ancient change”) has following microscopic features: Localized cells with large pleomorphic nuclei, cytoplasmic nuclear inclusions, smudgy chromatin, and inconspicuous nuclei. […] Positive for: S100 (weaker), SOX10, Neurofilament (and Bielshowsky), GFAP, CD34 (stronger), Factor XIIIa, Calretinin (focal), MBP (myelin-basic protein). […] Negative for: EMA (except in plexiform neurofibromas). […] Neurofibromatosis 1, Neurofibromatosis 2 (multiple neurofibromas, meningiomas of the brain or spinal cord, and ependymomas of the spinal cord). […] Can occur anywhere. […] Diffuse neurofibromas commonly involve scalp. […] Soft masses/bumps on or under skin (internal or superficial), Transient itching (mast cells release histamine), Transient pain, Numbness and tingling in the affected area, Severe bleeding (sign of tumor growth), Physical disfiguration, Cognitive disability, Stinging, Neurological deficits, Changes in movement (clumsiness in hands, trouble walking), Bowel incontinence, Scoliosis (an abnormal curvature of the spine, if the tumor creates muscular imbalance or erodes bones of the spine).

• #22 Neurofibroma differential diagnosis – wikidoc

  https://www.wikidoc.org/index.php/Neurofibroma_differential_diagnosis

  Neurofibroma can be sporadic or as a part of Neurofibromatosis 1 and 2. […] Neurofibroma with degenerative atypia („ancient change”) has following microscopic features: Localized cells with large pleomorphic nuclei, cytoplasmic nuclear inclusions, smudgy chromatin, and inconspicuous nuclei. […] Positive for: S100 (weaker), SOX10, Neurofilament (and Bielshowsky), GFAP, CD34 (stronger), Factor XIIIa, Calretinin (focal), MBP (myelin-basic protein). […] Negative for: EMA (except in plexiform neurofibromas). […] Neurofibromatosis 1, Neurofibromatosis 2 (multiple neurofibromas, meningiomas of the brain or spinal cord, and ependymomas of the spinal cord). […] Can occur anywhere. […] Diffuse neurofibromas commonly involve scalp. […] Soft masses/bumps on or under skin (internal or superficial), Transient itching (mast cells release histamine), Transient pain, Numbness and tingling in the affected area, Severe bleeding (sign of tumor growth), Physical disfiguration, Cognitive disability, Stinging, Neurological deficits, Changes in movement (clumsiness in hands, trouble walking), Bowel incontinence, Scoliosis (an abnormal curvature of the spine, if the tumor creates muscular imbalance or erodes bones of the spine).

• #23 Neurofibroma differential diagnosis – wikidoc

  https://www.wikidoc.org/index.php/Neurofibroma_differential_diagnosis

  Neurofibroma can be sporadic or as a part of Neurofibromatosis 1 and 2. […] Neurofibroma with degenerative atypia („ancient change”) has following microscopic features: Localized cells with large pleomorphic nuclei, cytoplasmic nuclear inclusions, smudgy chromatin, and inconspicuous nuclei. […] Positive for: S100 (weaker), SOX10, Neurofilament (and Bielshowsky), GFAP, CD34 (stronger), Factor XIIIa, Calretinin (focal), MBP (myelin-basic protein). […] Negative for: EMA (except in plexiform neurofibromas). […] Neurofibromatosis 1, Neurofibromatosis 2 (multiple neurofibromas, meningiomas of the brain or spinal cord, and ependymomas of the spinal cord). […] Can occur anywhere. […] Diffuse neurofibromas commonly involve scalp. […] Soft masses/bumps on or under skin (internal or superficial), Transient itching (mast cells release histamine), Transient pain, Numbness and tingling in the affected area, Severe bleeding (sign of tumor growth), Physical disfiguration, Cognitive disability, Stinging, Neurological deficits, Changes in movement (clumsiness in hands, trouble walking), Bowel incontinence, Scoliosis (an abnormal curvature of the spine, if the tumor creates muscular imbalance or erodes bones of the spine).

• #24 Neurofibromatosis type 1 – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/neurofibromatosis-type-1/diagnosis-treatment/drc-20350495

  To diagnose neurofibromatosis type 1 (NF1), a healthcare professional begins with a review of your personal and family medical history and a physical exam. […] Your child’s skin is checked for cafe au lait spots, which can help diagnose NF1. […] If other tests are needed to diagnose NF1, your child may need: Eye exam. An eye exam can reveal Lisch nodules, cataracts and vision loss. […] Imaging tests. X-rays, CT scans or MRIs can help identify bone changes, tumors in the brain or spinal cord, and very small tumors. An MRI might be used to diagnose optic gliomas. […] Genetic tests. Genetic testing for NF1 can help support the diagnosis. Genetic tests also can be done in pregnancy before a baby is born. Ask a member of your healthcare team about genetic counseling. […] For a diagnosis of NF1, at least two symptoms of the condition must be present. A child who has only one symptom and no family history of NF1 is likely to be monitored for any other symptoms. A diagnosis of NF1 is usually made by age 4.

• #25 Neurofibromatosis: Diagnosis & Treatment | NewYork-Presbyterian

  https://www.nyp.org/pediatrics/neurology-and-neurosurgery/neurofibromatosis/treatment

  How is Neurofibromatosis Diagnosed? Diagnosis To confirm a diagnosis of neurofibromatosis, a doctor and a genetic counselor do a comprehensive personal and family medical history review and a thorough neurologic and physical exam. […] Tests to diagnose NF1, NF2, or schwannomatosis include: […] Genetic tests. These are done to identify NF1 and NF2 and schwannomatosis mutations. If a parent has neurofibromatosis, genetic testing and counseling can be done during pregnancy. […] Imaging tests. X-rays, CT, or MRIs scans can help identify tumors in the brain, spinal cord, and ears and show bone abnormalities. Imaging tests are also used to monitor changes over time in NF2 and schwannomatosis. […] Eye exam. Eye doctors can assess for Lisch nodules, visual loss, and cataracts. […] In addition to imaging and genetic tests, additional tests may be done specifically for each type. Diagnosis of each type of neurofibromatosis includes:

• #26 Neurofibromatosis – AANS

  https://www.aans.org/patients/conditions-treatments/neurofibromatosis/

  NF1 manifests itself at birth or during early childhood. […] NF2 may appear during childhood, adolescence or early adulthood. […] NF1 is caused by mutations in the gene that controls production of a protein called neurofibromin (neurofibromin 1). […] NF2 results from mutations in a different tumor-suppressing gene (neurofibromin 2, merlin). […] Patients with NF2 should have similar routine examinations and care. […] There is no known treatment or cure for neurofibromatosis or schwannomatosis.

• #27 Genetic Testing for Neurofibromatosis and Related Disorders

  https://www.southcarolinablues.com/web/public/brands/medicalpolicyhb/external-policies/genetic-testing-for-neurofibromatosis-and-related-disorders/

  Neurofibromatoses are a group of three clinically and genetically distinct disorders that cause tumors to form on nerve tissue. […] Neurofibromatosis type 1 (NF1) is caused by autosomal dominant mutations in the neurofibromin (NF1) gene and is characterized by multiple caf-au-lait macules and neurofibromas (Korf et al., 2024). […] For individuals who are clinically suspected of having neurofibromatosis type 1 (NF1), but for whom a definitive diagnosis cannot be made without genetic testing, genetic testing for NF1 mutations is considered MEDICALLY NECESSARY when one of the following signs of NF1 is present: Individual has six or more caf-au-lait macules (over 5 mm in greatest diameter in pre-pubertal individuals; over 15 mm in greatest diameter in post-pubertal individuals). […] Molecular testing for NF1 includes sequencing of all the coding exons as well as deletions/rearrangements due to the large size of the gene and the heterogeneity of mutations.

• #28 Diagnosis – Neurofibromatosis Program

  https://www.uab.edu/medicine/nfprogram/learn-about-nf/nf1/diagnosis

  In cases where a diagnosis cannot be made based on the presence of physical symptoms, genetic testing for the NF1 gene mutation is currently available and may be appropriate for some families in order to confirm a diagnosis of NF1. A genetic counselor can provide guidance and information regarding the suitability of genetic testing in these cases.

• #29 Neurofibromatosis Type 1 Workup: Laboratory Studies, Imaging Studies, Other Tests

  https://emedicine.medscape.com/article/1177266-workup

  The diagnosis of neurofibromatosis type 1 (NF1) is usually made clinically, however, molecular testing may be helpful for younger patients with a single clinical finding, such as multiple caf-au-lait spots in the absence of a positive family history. […] Sequencing of the neurofibromin gene offers the highest detection rate and may approach 95% in clinically affected individuals. […] 97% of patients with NF1 are expected to meet clinical diagnosis by the age of 8 years. For those not meeting clinical criteria or for those that overlap with Legius Syndrome, molecular testing can be useful for confirmation. […] Neurofibromatosis type 1 (NF1) may be diagnosed by either of two methods during the prenatal period. […] In a family with multiple affected members, linkage analysis can track the NF1 gene through the generations to determine which chromosome 17 region the fetus received. However, with advances in molecular diagnosis, family studies are rarely necessary.

• #30 Athena Diagnostics

  https://www.athenadiagnostics.com/view-full-catalog/neurofibromatosis-type-i-nf1-evaluation1

  Test code: 648 Type of disorder: Neuro-Oncology Disease(s) tested for: Neurofibromatosis Type 1 Genes Included: NF1, NF1 Deletion, Tests included: Neurofibromatosis Type 1 Deletion TestNeurofibromatosis Type 1 DNA Sequencing Test Informed Consent Required: This test requires physician attestation that patient consent has been received […] Clinical Significance: Detects mutations in the NF1 gene Typical Presentation: Findings include neurofibromas, caf au lait spots, Lisch nodules, Inguinal and axillary freckling and optic gliomas with variability in severity. Indications for testing: Confirm a diagnosis in suspected cases when the patient does not meet the NIH diagnostic criteria. Early detection will allow for patient surveillance, genetic counseling, family planning. Methodology: Sanger Sequencing, Multiplex Ligation-dependent Probe Amplification (MLPA) Reference Range: No deletions or point mutations detected

• #31 Neurofibromatosis 1 – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1109/

  Neurofibromatosis 1 (NF1) is a multisystem disorder characterized by multiple caf au lait macules, intertriginous freckling, multiple cutaneous neurofibromas, and learning disability or behavior problems. […] The diagnosis of NF1 is established in a proband with two or more of the characteristic clinical features or one characteristic clinical feature and a heterozygous NF1 pathogenic variant. […] The diagnosis of NF1 is established in a proband with two or more of the features described in Suggestive Findings. […] If the phenotypic findings suggest the diagnosis of NF1, single-gene testing may be considered. […] Negative NF1 molecular testing does not rule out a diagnosis of NF1. […] Chromosomal microarray analysis (CMA) may be performed instead of sequence analysis to detect NF1 whole-gene deletions if the NF1 microdeletion phenotype is suspected clinically. […] The diagnosis of NF1 is established in a proband with two or more of the features described in Suggestive Findings. […] The diagnosis of NF1 is established in a proband with two or more of the features described in Suggestive Findings.

• #32 Neurofibroma differential diagnosis – wikidoc

  https://www.wikidoc.org/index.php/Neurofibroma_differential_diagnosis

  Neurofibroma must be differentiated from schwannoma, dermatofibrosarcoma protuberans (DFSP), ganglioneuroma, dermal neurotized melanocytic nevus, myxoid liposarcoma, solitary circumscribed neuroma, traumatic neuroma, superficial angiomyxoma, nerve sheath myxoma, malignant peripheral nerve sheath tumor, spindle cell lipoma, leiomyoma, inflammatory myofibroblastic tumor, and fibroepithelial polyp. […] Neurofibroma must be differentiated from: Schwannoma, Dermatofibrosarcoma protuberans (DFSP), Ganglioneuroma, Dermal neurotized melanocytic nevus, Myxoid liposarcoma, Solitary circumscribed neuroma/palisaded encapsulated neuroma, Traumatic neuroma, Superficial angiomyxoma, Nerve sheath myxoma, Malignant peripheral nerve sheath tumor (MPNST)/malignant schwannoma, Spindle cell lipoma, Leiomyoma, Inflammatory myofibroblastic tumor, Fibroepithelial polyp/acrochordon (aka skin tag or soft fibroma).

• #33 Genetic Testing for Neurofibromatosis and Related Disorders

  https://www.southcarolinablues.com/web/public/brands/medicalpolicyhb/external-policies/genetic-testing-for-neurofibromatosis-and-related-disorders/

  Molecular genetic testing is indicated for individuals in whom NF1 is suspected but who do not fulfill the NIH diagnostic criteria (Friedman, 2023). […] Prenatal testing is available through direct mutation testing of fetal DNA taken from CVS or from amniocentesis to diagnose NF1 pathogenic variants in the fetus. […] A negative NF1 mutation test in patients with only caf-au-lait macules and axillary freckling should be tested for SPRED1 mutations followed by the four mismatch repair genes as Legius syndrome, constitutional mismatch repair-deficiency (CMMR-D) syndrome, and Noonan syndrome may present with these indications (Korf et al., 2024). […] Diagnostic criteria for neurofibromatosis type 1: The diagnostic criteria for NF1 are met in an individual who does not have a parent diagnosed with NF1 if two or more of the following are present: Six or more caf-au-lait macules over 5 mm in greatest diameter in prepubertal individuals and over 15 mm in greatest diameter in postpubertal individuals.

• #34 Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation | Genetics in Medicine

  https://www.nature.com/articles/s41436-021-01170-5

  The current clinical diagnostic criteria have low sensitivity in children since diagnostic signs appear progressively over time. […] To increase the diagnostic rate in the age group 7 years and in the subgroup with only CALMs and skinfold freckling (with or without a family history) and no other clinical criteria, molecular diagnosis could be considered to confirm a diagnosis of NF1 or LGSS. […] Diagnosis of NF1 is confirmed when an NF1 PV is identified in an individual/fetus having either one or more of the other diagnostic criteria fulfilled. […] Mosaic NF1 in a patient is confirmed when an individual with features of NF1 carries a heterozygous NF1 PV in an unaffected tissue such as blood but in significantly less than 100% of cells (variant allele fraction [VAF]50%). […] The proposed criteria for diagnosis of NF1 and LGSS represent the first coordinated attempt by our community to update the diagnostic criteria since 1987.

• #35 Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation | Genetics in Medicine

  https://www.nature.com/articles/s41436-021-01170-5

  By incorporating major developments in genetics, ophthalmology, dermatology, and neuroimaging, to revise the diagnostic criteria for neurofibromatosis type 1 (NF1) and to establish diagnostic criteria for Legius syndrome (LGSS). […] We reached consensus on the minimal clinical and genetic criteria for diagnosing and differentiating NF1 and LGSS, which have phenotypic overlap in young patients with pigmentary findings. […] The revised criteria for NF1 incorporate new clinical features and genetic testing, whereas the criteria for LGSS were created to differentiate the two conditions. […] The identification of LGSS highlights an important limitation of the NIH NF1 clinical diagnostic criteria. […] Ultimately, consensus was reached on the minimal clinical and genetic criteria for diagnosing NF1 and LGSS.

• #36 Neurofibromatosis Type 1: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1177266-overview

  Neurofibromatosis type 1 (NF1) is a multisystem genetic disorder that is characterized by cutaneous findings, most notably caf-au-lait spots and axillary freckling, by skeletal dysplasias, and by the growth of both benign and malignant nervous system tumors, most notably benign neurofibromas. […] An international consensus revised the diagnostic criteria for NF1 in 2021. In the absence of a parent with NF1, the criteria for clinical diagnosis includes two or more of the following: Six or more caf-au-lait (CAL) macules greater than 5 mm in diameter in prepubertal children and greater than 15 mm postpubertal; Axillary or inguinal freckles (2 freckles) (if only CAL and freckling are present, one of these two cutaneous manifestations should be bilateral, and Legius syndrome should be considered, though the diagnosis is still likely NF1); Two or more typical neurofibromas or one plexiform neurofibroma; Optic pathway glioma; Two or more iris hamartomas (Lisch nodules), often identified only through slit-lamp examination by an ophthalmologist; or two or more choroidal abnormalities; Sphenoid dysplasia or typical long-bone abnormalities such as pseudarthrosis; Heterozygous pathogenic NF1 variant with a variant allele fraction of 50% in apparently normal tissue. […] In the presence of a parent with NF1, the criteria for clinical diagnosis include one of the above criteria.

• #37 Neurofibromatosis Type 1: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1177266-overview

  Neurofibromatosis type 1 (NF1) is a multisystem genetic disorder that is characterized by cutaneous findings, most notably caf-au-lait spots and axillary freckling, by skeletal dysplasias, and by the growth of both benign and malignant nervous system tumors, most notably benign neurofibromas. […] An international consensus revised the diagnostic criteria for NF1 in 2021. In the absence of a parent with NF1, the criteria for clinical diagnosis includes two or more of the following: Six or more caf-au-lait (CAL) macules greater than 5 mm in diameter in prepubertal children and greater than 15 mm postpubertal; Axillary or inguinal freckles (2 freckles) (if only CAL and freckling are present, one of these two cutaneous manifestations should be bilateral, and Legius syndrome should be considered, though the diagnosis is still likely NF1); Two or more typical neurofibromas or one plexiform neurofibroma; Optic pathway glioma; Two or more iris hamartomas (Lisch nodules), often identified only through slit-lamp examination by an ophthalmologist; or two or more choroidal abnormalities; Sphenoid dysplasia or typical long-bone abnormalities such as pseudarthrosis; Heterozygous pathogenic NF1 variant with a variant allele fraction of 50% in apparently normal tissue. […] In the presence of a parent with NF1, the criteria for clinical diagnosis include one of the above criteria.

• #38 Table: Diagnosing Neurofibromatosis-Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/multimedia/table/diagnosing-neurofibromatosis

  Diagnosing Neurofibromatosis […] If the patient has a parent diagnosed with NF1 and meets at least 1 of the criteria below, the diagnosis of NF1 is made. […] If the patient does not have a parent diagnosed with NF1, 2 of the following must be present: […] 2 neurofibromas of any type or 1 plexiform neurofibroma. […] NF2-related schwannomatosis (NF2) 1 of the following: […] An identical NF2 pathogenic variant in at least 2 anatomically distinct NF2-related tumors (schwannoma, meningioma, and/or ependymoma). […] Major criteria (2 of the following): […] NF2 pathogenic variant in an unaffected tissue (eg, blood). […] One major criterion and 2 of the following minor criteria: […] Pattern of genetic changes in unaffected tissue and in tumor tissue in NF2. […] Non-NF2 schwannomatosis (schwannomatosis) SMARCB1- and LZTR1-related schwannomatosis (1 of the following):

• #39 Neurofibromatosis Type 1: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1177266-overview

  Neurofibromatosis type 1 (NF1) is a multisystem genetic disorder that is characterized by cutaneous findings, most notably caf-au-lait spots and axillary freckling, by skeletal dysplasias, and by the growth of both benign and malignant nervous system tumors, most notably benign neurofibromas. […] An international consensus revised the diagnostic criteria for NF1 in 2021. In the absence of a parent with NF1, the criteria for clinical diagnosis includes two or more of the following: Six or more caf-au-lait (CAL) macules greater than 5 mm in diameter in prepubertal children and greater than 15 mm postpubertal; Axillary or inguinal freckles (2 freckles) (if only CAL and freckling are present, one of these two cutaneous manifestations should be bilateral, and Legius syndrome should be considered, though the diagnosis is still likely NF1); Two or more typical neurofibromas or one plexiform neurofibroma; Optic pathway glioma; Two or more iris hamartomas (Lisch nodules), often identified only through slit-lamp examination by an ophthalmologist; or two or more choroidal abnormalities; Sphenoid dysplasia or typical long-bone abnormalities such as pseudarthrosis; Heterozygous pathogenic NF1 variant with a variant allele fraction of 50% in apparently normal tissue. […] In the presence of a parent with NF1, the criteria for clinical diagnosis include one of the above criteria.

• #40 Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation | Genetics in Medicine

  https://www.nature.com/articles/s41436-021-01170-5

  The current clinical diagnostic criteria have low sensitivity in children since diagnostic signs appear progressively over time. […] To increase the diagnostic rate in the age group 7 years and in the subgroup with only CALMs and skinfold freckling (with or without a family history) and no other clinical criteria, molecular diagnosis could be considered to confirm a diagnosis of NF1 or LGSS. […] Diagnosis of NF1 is confirmed when an NF1 PV is identified in an individual/fetus having either one or more of the other diagnostic criteria fulfilled. […] Mosaic NF1 in a patient is confirmed when an individual with features of NF1 carries a heterozygous NF1 PV in an unaffected tissue such as blood but in significantly less than 100% of cells (variant allele fraction [VAF]50%). […] The proposed criteria for diagnosis of NF1 and LGSS represent the first coordinated attempt by our community to update the diagnostic criteria since 1987.

• #41 Neurofibromatosis type 1 — Knowledge Hub

  https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/neurofibromatosis-type-1/

  Neurofibromatosis type 1 (NF1) is characterised by an early presentation of multiple caf-au-lait macules and, later, benign growths known as neurofibromas. […] Revised diagnostic criteria suggest that a diagnosis of NF1 can be made in a patient without a family history when two or more of the following features are present: […] two or more neurofibromas or one plexiform neurofibroma. […] If no NF1 variant is identified in the blood, testing of affected tissue (for example, via skin biopsy of a lesion) may be considered. […] NF1 is an autosomal dominant condition. […] There is a one-in-two (50%) chance that a child of an individual with a pathogenic variant in NF1 will inherit the condition. […] Management of children with NF1 is complex and should be delivered via a multidisciplinary team.

• #42 Prenatal diagnosis for neurofibromatosis type 1 and the pitfalls of germline mosaics | npj Genomic Medicine

  https://www.nature.com/articles/s41525-024-00425-9

  Another option is preimplantation genetic testing. PND and preimplantation genetic testing for a pregnancy at increased risk are possible if the disease-causing variant is known, or if there are multiple affected family members, and linkage has been established within the family; such testing is useful for establishing the presence of the parental mutation in the fetal DNA, but as noted, cannot make any prediction about disease severity. […] This study illustrates the value of PND in NF1, with crucial consequences for medical and genetic counseling decisions. Our observations also point to the challenges that may be associated with germline mosaics. […] In both families, direct PND analysis (CVS) showed the absence of the maternal NF1 pathogenic variant in the fetus. However, microsatellite markers analysis showed that the risk haplotype (associated with the NF1 pathogenic variant in the affected parent) had been transmitted. These rare cases of germline mosaicism illustrate the pitfall of indirect PND.

• #43 Neurofibromatosis Type 1 Workup: Laboratory Studies, Imaging Studies, Other Tests

  https://emedicine.medscape.com/article/1177266-workup

  The diagnosis of neurofibromatosis type 1 (NF1) is usually made clinically, however, molecular testing may be helpful for younger patients with a single clinical finding, such as multiple caf-au-lait spots in the absence of a positive family history. […] Sequencing of the neurofibromin gene offers the highest detection rate and may approach 95% in clinically affected individuals. […] 97% of patients with NF1 are expected to meet clinical diagnosis by the age of 8 years. For those not meeting clinical criteria or for those that overlap with Legius Syndrome, molecular testing can be useful for confirmation. […] Neurofibromatosis type 1 (NF1) may be diagnosed by either of two methods during the prenatal period. […] In a family with multiple affected members, linkage analysis can track the NF1 gene through the generations to determine which chromosome 17 region the fetus received. However, with advances in molecular diagnosis, family studies are rarely necessary.

• #44 Neurofibromatosis | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/neurofibromatosis

  Can NF1 be diagnosed during pregnancy? […] If a parent has NF1 and a known mutation, testing can be performed to determine if the baby has inherited the same mutation. But keep in mind that even if the test shows the mutation, it is difficult to know anything about what symptoms the child will develop. Prenatal diagnosis can be done through: chorionic villus sampling (CVS) typically at 10-12 weeks gestation, amniocentesis (tests the amniotic fluid) typically at 14-15 weeks gestation. […] Neurofibromatosis | Treatments […] At Boston Children’s Hospital, we know how overwhelming a diagnosis of neurofibromatosis can feel, both for your child and for your whole family. Please be assured that your child’s doctors will have an ongoing relationship with your child and your family, and that we’ll walk through this journey together. Since a cure for NF has not yet been found, treatment focuses on managing symptoms. This means that we’ll customize a treatment plan based on your child’s needs, and update it whenever those needs change.

• #45 Prenatal diagnosis for neurofibromatosis type 1 and the pitfalls of germline mosaics | npj Genomic Medicine

  https://www.nature.com/articles/s41525-024-00425-9

  We report our 5-year experience in neurofibromatosis type 1 prenatal diagnosis (PND): 205 PNDs in 146 women (chorionic villus biopsies, 88% or amniocentesis, 12%). The NF1 variant was present in 85 (41%) and absent in 122 (59%) fetuses. […] Our study illustrates the crucial consequences of PND for medical and genetic counseling decisions. We also point to the challenges of germline mosaics. […] Molecular analysis of the NF1 gene is important in clinical practice to confirm the diagnosis, to differentiate from phenocopies (such as Legius syndrome; MIM#611431) and to allow genetic counseling. […] In fact, NF1 is considered fully penetrant by the age of eight years with extremely variable clinical manifestations, even within families carrying the same variant. […] The unpredictable clinical expression in offspring can complicate reproductive decision-making for NF1 patients and their partners.

• #46 Neurofibromatosis | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/neurofibromatosis

  Can NF1 be diagnosed during pregnancy? […] If a parent has NF1 and a known mutation, testing can be performed to determine if the baby has inherited the same mutation. But keep in mind that even if the test shows the mutation, it is difficult to know anything about what symptoms the child will develop. Prenatal diagnosis can be done through: chorionic villus sampling (CVS) typically at 10-12 weeks gestation, amniocentesis (tests the amniotic fluid) typically at 14-15 weeks gestation. […] Neurofibromatosis | Treatments […] At Boston Children’s Hospital, we know how overwhelming a diagnosis of neurofibromatosis can feel, both for your child and for your whole family. Please be assured that your child’s doctors will have an ongoing relationship with your child and your family, and that we’ll walk through this journey together. Since a cure for NF has not yet been found, treatment focuses on managing symptoms. This means that we’ll customize a treatment plan based on your child’s needs, and update it whenever those needs change.

• #47 Prenatal diagnosis for neurofibromatosis type 1 and the pitfalls of germline mosaics | npj Genomic Medicine

  https://www.nature.com/articles/s41525-024-00425-9

  Another option is preimplantation genetic testing. PND and preimplantation genetic testing for a pregnancy at increased risk are possible if the disease-causing variant is known, or if there are multiple affected family members, and linkage has been established within the family; such testing is useful for establishing the presence of the parental mutation in the fetal DNA, but as noted, cannot make any prediction about disease severity. […] This study illustrates the value of PND in NF1, with crucial consequences for medical and genetic counseling decisions. Our observations also point to the challenges that may be associated with germline mosaics. […] In both families, direct PND analysis (CVS) showed the absence of the maternal NF1 pathogenic variant in the fetus. However, microsatellite markers analysis showed that the risk haplotype (associated with the NF1 pathogenic variant in the affected parent) had been transmitted. These rare cases of germline mosaicism illustrate the pitfall of indirect PND.

• #48 Neurofibromatosis type 1 — Knowledge Hub

  https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/neurofibromatosis-type-1/

  Neurofibromatosis type 1 (NF1) is characterised by an early presentation of multiple caf-au-lait macules and, later, benign growths known as neurofibromas. […] Revised diagnostic criteria suggest that a diagnosis of NF1 can be made in a patient without a family history when two or more of the following features are present: […] two or more neurofibromas or one plexiform neurofibroma. […] If no NF1 variant is identified in the blood, testing of affected tissue (for example, via skin biopsy of a lesion) may be considered. […] NF1 is an autosomal dominant condition. […] There is a one-in-two (50%) chance that a child of an individual with a pathogenic variant in NF1 will inherit the condition. […] Management of children with NF1 is complex and should be delivered via a multidisciplinary team.

• #49 Treatment & Management – Neurofibromatosis Program

  https://www.uab.edu/medicine/nfprogram/learn-about-nf/nf1/treatment-management

  There is currently no cure or treatment for NF1 that can reverse or prevent most complications. Because of this, medical management of the condition focuses on the early detection of treatable complications. This often includes surgery to remove or reduce the size of neurofibromas and the evaluation and management of learning disabilities. […] In general, a person diagnosed with or suspected of having NF1 should have a complete medical evaluation at least once a year. This exam should be performed by a physician familiar with the disorder and connected to appropriate medical consultants and specialists who can assist with specific problems that may be found. […] Comprehensive eye examinations are an important part of managing NF1. A distinct feature of NF1 called Lisch nodules small bumps on the iris of the eye can help in establishing a diagnosis of NF1. Examining the eye for Lisch nodules requires a specialized tool called a slit lamp and is usually performed by a specialist. […] Sometimes the signs or symptoms of bone and neurological problems require further investigation using imaging tests such as a CT or MRI scan of the brain.

• #50 Neurofibromatosis | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/neurofibromatosis

  Follow-up […] Whether your child has received a diagnosis of NF1 or has yet to meet the diagnosis, the doctors in our Neurofibromatosis Program will see her at least once per year, and arrange more frequent follow-up visits if necessary. Younger children are often seen once every six months. When your child comes to our clinic, we’ll: examine her skin, get an update of her medical history, check her blood pressure, monitor her height and weight, do a developmental assessment and/or review her school progress (if she’s of school age), conduct additional tests as appropriate, arrange for her to see other Boston Children’s specialists if appropriate. […] If you have any questions about interim follow-up visits, our clinical coordinator will be happy to talk with you.

• #51 Guidelines for the diagnosis and management of individuals with neurofibromatosis 1

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2598063/

  Neurofibromatosis 1 (NF1) is a common neurocutaneous condition with an autosomal dominant pattern of inheritance. The diagnosis is based on clinical assessment and two or more of the features in table 1 are required. These diagnostic criteria are robust and have stood the test of time well. Clinicians should be aware that some individuals with mosaic/segmental NF1 fulfil the diagnostic criteria as they present with six or more caf au lait patches with skinfold freckling or neurofibromas. NF1 has a birth incidence of 1 in 2500 to 1 in 3000. Approximately half of NF1 sufferers are the first in their family to have the condition. Children with six caf au lait patches alone and no family history should be followed up as if they have the disease, as 95% of them will develop NF1. NF1 mutational analysis clarifies the diagnosis in some uncertain cases and in individuals contemplating prenatal diagnosis. However, genetic testing is not advocated routinely and expert consultation is advised before it is undertaken. Hyperintense lesions on T2 weighted brain MRI are probably caused by aberrant myelination or gliosis, and are pathognomonic of NF1. The presence of these lesions can assist the diagnosis of NF1 but MRI under anaesthetic is not warranted for this purpose in young children. The differential diagnoses of NF1 include other forms of neurofibromatosis, conditions with caf au lait patches or with pigment changes confused with caf au lait patches. The only subtype of NF1 that is distinct and has a uniform phenotype in families is Watson syndrome. NF2 is an autosomal dominant neurocutaneous disease that is clinically and genetically distinct from NF1 and occurs in approximately 1 in 25000 individuals. It is caused by inactivating mutations on chromosome 22q11.2 and is characterised by bilateral vestibular schwannomas. Affected individuals also develop schwannomas on other cranial, spinal, peripheral and cutaneous nerves. The mainstay of management is age specific monitoring of disease manifestations and patient education. NF1 individuals need to be encouraged to seek review of any unusual symptoms and ask if they are related to NF1. All children with uncomplicated disease need to be assessed once a year, ideally by one paediatrician in each area to facilitate coordinated care. Monitoring after the midtwenties depends on patient preference and disease severity. Adults with severe disease have usually been identified by this stage and require lifelong monitoring in an NF1 clinic. The manifestations of NF1 are widespread and affect many of the body systems. Neurofibromas are benign peripheral nerve sheath tumours that are focal cutaneous or subcutaneous, or diffuse or nodular plexiform lesions. Cutaneous neurofibromas are found in the majority of NF1 individuals, usually develop in the late teens or early twenties but occasionally emerge in early childhood. There have been no reports of these skin tumours undergoing malignant change but they often catch on clothing and cause cosmetic problems, transient stinging and itching. Referral to surgeons skilled in the removal of neurofibromas is advocated and plastic surgeons should be consulted for neurofibromas on the face and neck. There is no proven benefit of carbon dioxide laser treatment over surgical removal of troublesome neurofibromas but laser may be helpful for some small lesions. There is an 813% lifetime risk of developing MPNST in NF1, predominantly in individuals aged 2035 years. NF1 patients should seek an urgent expert opinion from specialist neurofibromatosis clinics or soft tissue tumour units if they develop any of the following in association with a subcutaneous or plexiform neurofibroma: persistent pain lasting for longer than a month or pain that disturbs sleep; new or unexplained neurological deficit or sphincter disturbance; alteration in the texture of a neurofibroma from soft to hard; and rapid increase in the size of a neurofibroma. Individuals who have been treated with radiotherapy, have a personal or family history of cancer, optic pathway glioma, whole gene deletion, multiple subcutaneous neurofibromas or neurofibromatous neuropathy might have an increased risk of developing MPNST and require careful clinical monitoring. The aim of treatment is complete removal of the lesion with tumour free margins. Adjuvant radiotherapy has a role in treating MPNST larger than 5cm, high grade lesions and incompletely excised tumours.

• #52 Guidelines for the diagnosis and management of individuals with neurofibromatosis 1

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2598063/

  Neurofibromatosis 1 (NF1) is a common neurocutaneous condition with an autosomal dominant pattern of inheritance. The diagnosis is based on clinical assessment and two or more of the features in table 1 are required. These diagnostic criteria are robust and have stood the test of time well. Clinicians should be aware that some individuals with mosaic/segmental NF1 fulfil the diagnostic criteria as they present with six or more caf au lait patches with skinfold freckling or neurofibromas. NF1 has a birth incidence of 1 in 2500 to 1 in 3000. Approximately half of NF1 sufferers are the first in their family to have the condition. Children with six caf au lait patches alone and no family history should be followed up as if they have the disease, as 95% of them will develop NF1. NF1 mutational analysis clarifies the diagnosis in some uncertain cases and in individuals contemplating prenatal diagnosis. However, genetic testing is not advocated routinely and expert consultation is advised before it is undertaken. Hyperintense lesions on T2 weighted brain MRI are probably caused by aberrant myelination or gliosis, and are pathognomonic of NF1. The presence of these lesions can assist the diagnosis of NF1 but MRI under anaesthetic is not warranted for this purpose in young children. The differential diagnoses of NF1 include other forms of neurofibromatosis, conditions with caf au lait patches or with pigment changes confused with caf au lait patches. The only subtype of NF1 that is distinct and has a uniform phenotype in families is Watson syndrome. NF2 is an autosomal dominant neurocutaneous disease that is clinically and genetically distinct from NF1 and occurs in approximately 1 in 25000 individuals. It is caused by inactivating mutations on chromosome 22q11.2 and is characterised by bilateral vestibular schwannomas. Affected individuals also develop schwannomas on other cranial, spinal, peripheral and cutaneous nerves. The mainstay of management is age specific monitoring of disease manifestations and patient education. NF1 individuals need to be encouraged to seek review of any unusual symptoms and ask if they are related to NF1. All children with uncomplicated disease need to be assessed once a year, ideally by one paediatrician in each area to facilitate coordinated care. Monitoring after the midtwenties depends on patient preference and disease severity. Adults with severe disease have usually been identified by this stage and require lifelong monitoring in an NF1 clinic. The manifestations of NF1 are widespread and affect many of the body systems. Neurofibromas are benign peripheral nerve sheath tumours that are focal cutaneous or subcutaneous, or diffuse or nodular plexiform lesions. Cutaneous neurofibromas are found in the majority of NF1 individuals, usually develop in the late teens or early twenties but occasionally emerge in early childhood. There have been no reports of these skin tumours undergoing malignant change but they often catch on clothing and cause cosmetic problems, transient stinging and itching. Referral to surgeons skilled in the removal of neurofibromas is advocated and plastic surgeons should be consulted for neurofibromas on the face and neck. There is no proven benefit of carbon dioxide laser treatment over surgical removal of troublesome neurofibromas but laser may be helpful for some small lesions. There is an 813% lifetime risk of developing MPNST in NF1, predominantly in individuals aged 2035 years. NF1 patients should seek an urgent expert opinion from specialist neurofibromatosis clinics or soft tissue tumour units if they develop any of the following in association with a subcutaneous or plexiform neurofibroma: persistent pain lasting for longer than a month or pain that disturbs sleep; new or unexplained neurological deficit or sphincter disturbance; alteration in the texture of a neurofibroma from soft to hard; and rapid increase in the size of a neurofibroma. Individuals who have been treated with radiotherapy, have a personal or family history of cancer, optic pathway glioma, whole gene deletion, multiple subcutaneous neurofibromas or neurofibromatous neuropathy might have an increased risk of developing MPNST and require careful clinical monitoring. The aim of treatment is complete removal of the lesion with tumour free margins. Adjuvant radiotherapy has a role in treating MPNST larger than 5cm, high grade lesions and incompletely excised tumours.

• #53 Guidelines for the diagnosis and management of individuals with neurofibromatosis 1 | Journal of Medical Genetics

  https://jmg.bmj.com/content/44/2/81

  It is recommended that multidisciplinary neurofibromatosis clinics include a lead clinician, named consultants who are experts in their field and a specialist nurse. […] Close collaboration between NF1 clinicians will facilitate a uniform approach to the diagnosis and management of NF1 and its complications.

• #54 Neurofibromatosis type 1 — Knowledge Hub

  https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/neurofibromatosis-type-1/

  Neurofibromatosis type 1 (NF1) is characterised by an early presentation of multiple caf-au-lait macules and, later, benign growths known as neurofibromas. […] Revised diagnostic criteria suggest that a diagnosis of NF1 can be made in a patient without a family history when two or more of the following features are present: […] two or more neurofibromas or one plexiform neurofibroma. […] If no NF1 variant is identified in the blood, testing of affected tissue (for example, via skin biopsy of a lesion) may be considered. […] NF1 is an autosomal dominant condition. […] There is a one-in-two (50%) chance that a child of an individual with a pathogenic variant in NF1 will inherit the condition. […] Management of children with NF1 is complex and should be delivered via a multidisciplinary team.

• #55 Guidelines for the diagnosis and management of individuals with neurofibromatosis 1 | Journal of Medical Genetics

  https://jmg.bmj.com/content/44/2/81

  It is recommended that multidisciplinary neurofibromatosis clinics include a lead clinician, named consultants who are experts in their field and a specialist nurse. […] Close collaboration between NF1 clinicians will facilitate a uniform approach to the diagnosis and management of NF1 and its complications.

• #56

  https://www.mountelizabeth.com.sg/conditions-diseases/neurofibroma/diagnosis-treatment

  Diagnosis of neurofibroma typically involves a combination of: […] Medical history and physical examination, focusing on visible tumours and neurological symptoms […] Imaging studies such as MRI or CT scans to identify the extent and location of deep-seated tumours […] Biopsy of the tumour, if necessary, to confirm the diagnosis and rule out malignancy […] Genetic testing, particularly in individuals with a family history of NF1, to identify mutations in the NF1 gene.

• #57 Neurofibromatosis – Wikipedia

  https://en.wikipedia.org/wiki/Neurofibromatosis

  Diagnosis is typically based on symptoms, examination, medical imaging, and biopsy. […] Genetic testing may rarely be done to support the diagnosis. […] The diagnosis of neurofibromatosis is done via the following means: Radiograph, MRI or CT scan, EEG, Slit-lamp examination, Genetic testing, Histology.

• #58 Diagnosing Neurofibromatosis in Children | Children’s Pittsburgh

  https://www.chp.edu/our-services/brain/neurology/neurofibromatosis/diagnosis

  Doctors often use MRI scans to diagnose neurofibromatosis. […] The Neuroradiology section of the Department of Pediatric Radiology, part of Childrens Hospitals Brain Care Institute, offers the latest testing and diagnostic technologies, including: […] To receive a NF1 diagnosis, a person must have at least two of the symptoms that can be associated with this disease. […] Children with a NF2 diagnosis have fewer outward signs of the condition than individuals with NF1. […] Recently, direct gene testing has become available, meaning that a patient’s blood can be tested effectively without obtaining blood samples from other relatives.

• #59 Neurofibromatosis Testing and Skin Treatment | H Weinberg MD

  https://www.hweinbergplasticsurgery.com/resources-info/testing-for-neurofibromatosis.html

  Doctors diagnose neurofibromatosis based on a combination of findings, including having a family history of the disease. […] They also look for typical signs and symptoms of the disease, order and review imaging studies, and sometimes order genetic testing. […] Some of these tests confirm a diagnosis of NF, help doctors know which of the three main types of NF a patient has or rule out NF. […] Neurofibromatosis Genetic Testing is helpful when a clinical diagnosis is inconclusive. […] It may be necessary to remove a tumor or section of tumor and examine it under a microscope to confirm the diagnosis of Schwannomatosis. […] Imaging tests can be used to monitor NF 1 and Schwannomatosis. […] There are many ongoing and new studies being performed for NF genetic disorders. […] It is important to have a neurofibromatosis specialist evaluate you or your child in order to help prevent additional damage caused by enlarging tumors. […] Working with a specialist also ensures that patients have access to new medical findings and treatment options as they become available.

• #60 Neurofibromatosis type 1 (NF1)

  https://www.rch.org.au/kidsinfo/fact_sheets/Neurofibromatosis/

  NF1 (also known as von Recklinghausen disease) is the most common type, affecting an estimated one in 3000 people in Australia. […] A diagnosis can be made by the doctor following a thorough history and examination. Other tests may be ordered to determine what parts of the body are affected. A blood test can be ordered but is not necessary to make a diagnosis. […] There is currently no cure for NF1. Most people with NF1 have no or few medical problems and live normal lives, with no need for treatment. However, because every person with NF1 is at risk of complications from this disorder, it is important that they are regularly reviewed by a doctor who is familiar with the condition. […] It is very important that children with NF1 have their eyes checked regularly, as they are at risk of developing optic gliomas. Optic gliomas are small tumours on the nerves behind the eyes. The tumours are benign, but can affect vision by putting pressure on the nerves. Optic gliomas can be treated if detected early. […] Although there is no cure at the moment, the gene that causes NF1 has been identified. A lot of research is being carried out in this area and there is a realistic hope for more effective treatments for the complications of NF1 within the next five to 10 years.

• #61 Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation | Genetics in Medicine

  https://www.nature.com/articles/s41436-021-01170-5

  The current clinical diagnostic criteria have low sensitivity in children since diagnostic signs appear progressively over time. […] To increase the diagnostic rate in the age group 7 years and in the subgroup with only CALMs and skinfold freckling (with or without a family history) and no other clinical criteria, molecular diagnosis could be considered to confirm a diagnosis of NF1 or LGSS. […] Diagnosis of NF1 is confirmed when an NF1 PV is identified in an individual/fetus having either one or more of the other diagnostic criteria fulfilled. […] Mosaic NF1 in a patient is confirmed when an individual with features of NF1 carries a heterozygous NF1 PV in an unaffected tissue such as blood but in significantly less than 100% of cells (variant allele fraction [VAF]50%). […] The proposed criteria for diagnosis of NF1 and LGSS represent the first coordinated attempt by our community to update the diagnostic criteria since 1987.

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