Materiały źródłowe

• #1 Diagnosing Neurofibromatosis | NYU Langone Health

  https://nyulangone.org/conditions/neurofibromatosis/diagnosis

  To diagnose any of the three types of neurofibromatosis, doctors conduct a physical exam, take a medical history, and may perform imaging tests and genetic tests. […] Neurofibromatosis type 1 can usually be identified with a physical exam, in which your doctor looks for signs of the condition such as light-brown caf-au-lait spots or tumors on the skin. […] About 97 percent of those with neurofibromatosis type 1 have enough features of the disorder to make the diagnosis by the time a child is eight years old. […] The National Institutes of Health have developed guidelines for diagnosing neurofibromatosis type 1. According to these criteria, the condition is present when a person has two or more of the following signs: six or more caf-au-lait spots larger than 5 mm across before puberty and larger than 15 mm across after puberty, two or more neurofibromas of any type or one plexiform neurofibroma, freckling of the skin in the underarm or groin areas, a tumor of the optic pathway, two or more Lisch nodules, a distinctive bone malformation, or a first-degree relative who also meets these criteria. […] A blood test is available for genetic testing to see whether a mutation in the neurofibromatosis type 1 gene is present. A diagnosis of neurofibromatosis type 1 is still possible in people who don’t have an identifiable mutation.

• #2 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.

• #3 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 […] 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 […] In the presence of a parent with NF1, the criteria for clinical diagnosis include one of the above criteria. […] Diagnosis often is made earlier in children born to an NF1-affected parent; the clinical criteria for diagnosis are fulfilled more easily, and the clinician may be more attuned to this possible diagnostic concern. […] If an at-risk individual reaches the age of 10 years without meeting the diagnostic criteria for NF1, he or she is unlikely to be affected.

• #4 2021 NF1 Diagnostic Criteria Update – Neurofibromatosis Midwest

  https://www.nfmidwest.org/blog/2021-nf1-diagnostic-criteria-update/

  An update of the diagnostic criteria for neurofibromatosis type 1 has just been published in Genetics in Medicine, the official journal of the American College of Medical Genetics and Genomics. […] The goal of the new criteria is to allow for earlier and more accurate diagnosis of NF1, leading to improved care. […] A diagnosis of NF1 can be given if an individual has two or more of the following manifestations: Six or more caf-au-lait macules (brown skin spots) greater than 5mm in pre-pubertal children greater than 15mm in post-pubertal individuals Freckling in axilla (armpit) or groin Two or more neurofibroma tumors of any type, or one plexiform neurofibroma Two or more iris Lisch nodules (iris hamartomas) Optic glioma A distinctive bony lesion: dysplasia (abnormal growth) of the sphenoid bone behind the eye, or dysplasia of long bones, often in the lower leg Having a close relative (parent, sibling, or child) with NF1

• #5 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. […] The current clinical diagnostic criteria have low sensitivity in children since diagnostic signs appear progressively over time.

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

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

  Diagnosing Neurofibromatosis […] Neurofibromatosis type 1 (NF1) […] 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: […] 6 caf-au-lait macules 5 mm in greatest diameter in prepubertal patients and 15 mm in greatest diameter in postpubertal patients […] Freckling in the axillary or inguinal region […] 2 neurofibromas of any type or 1 plexiform neurofibroma […] Optic pathway glioma […] 2 Lisch nodules (iris hamartomas) identified by slit-lamp examination or 2 choroidal abnormalities […] A distinctive osseous lesion (eg, sphenoid dysplasia, anterolateral bowing of the tibia, pseudarthrosis of a long bone) […] A heterozygous pathogenic NF1 variant with a 50% variant allele fraction in apparently normal tissue (eg, white blood cells).

• #7 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

  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. […] NF1 experts agreed that identification of an NF1 variant alone does not suffice to make a diagnosis of NF1 but does require further clinical and genetic evaluation: the variant must be confirmed as pathogenic using an orthogonal method; further genetic analysis is required to verify if the variant is present as a constitutional (germline), mosaic (which may result in a mild phenotype), or somatic variant.

• #8 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.

• #9 2021 NF1 Diagnostic Criteria Update – Neurofibromatosis Midwest

  https://www.nfmidwest.org/blog/2021-nf1-diagnostic-criteria-update/

  A diagnosis of NF1 can be given if an individual has two or more of the following manifestations: Six or more caf-au-lait-macules (brown skin spots) greater than 5mm in pre-pubertal children greater than 15mm in post-pubertal individuals Freckling in axilla (armpit) or groin Two or more neurofibroma tumors of any type, or one plexiform neurofibroma Two or more Lisch nodules or two or more choroidal abnormalities Optic pathway glioma (tumor of the visual pathway) A distinctive osseous lesion such as: sphenoid dysplasia; anterolateral bowing of tibia (tibial dysplasia); or pseudarthrosis of a long bone A pathogenic NF1 gene variant A parent with NF1 by the above criteria.

• #10 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.

• #11 Neurofibromatosis | National Institute of Neurological Disorders and Stroke

  https://www.ninds.nih.gov/health-information/disorders/neurofibromatosis

  While NF1 is rare, it is the most common type of NF. Symptoms can develop slowly, so getting the correct diagnosis may take several years. But most people are diagnosed during early childhood. […] To diagnose neurofibromatosis (NF), a doctor begins with a review of a patients personal and family medical history and a physical exam. Doctors can check for characteristic signs and symptoms to diagnose a person suspected of having NF. […] NF1 is usually diagnosed during childhood, as symptoms appear at birth or shortly after, usually by age 10. To make a diagnosis of NF1, an individual must have two or more of the following: […] Doctors will likely monitor a child with only one symptom and no family history of NF1 for any other symptoms. To diagnose NF1 using skin changes (caf au lait spots or freckling), at least one of these skin conditions needs to appear on both sides of the body.

• #11 Neurofibromatosis | National Institute of Neurological Disorders and Stroke

  https://www.ninds.nih.gov/health-information/disorders/neurofibromatosis

  An eye exam can help diagnose neurofibromatosis and show Lisch nodules, cataracts, and vision loss caused by NF1. To diagnose NF2 and SWN, doctors may order hearing tests. […] Imaging tests such as X-rays, CT scans (computed tomography scan), or MRIs (magnetic resonance imaging) can help identify bone changes, tumors in the brain or spinal cord, and very small tumors elsewhere in the body. […] Genetic testing may be needed to correctly diagnose individuals with features of these conditions who do not have a known family history or bilateral vestibular schwannomas (those that happen on both sides of the body). Genetic testing can be useful in some situations, such as when a person is pregnant or when the clinical diagnosis is inconclusive.

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

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

  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. […] 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. […] Electroencephalogram (EEG) is indicated in patients with symptoms suggestive of seizures. […] MRI alone is generally sufficient for medical and/or surgical decision making. Occasionally, myelography is needed to clarify the extent of a spinal cord tumor. […] Slit-lamp examination by an experienced ophthalmologist can provide key diagnostic information in older children and adults who have only a single clinical criterion such as multiple caf-au-lait spots.

• #13 Visual Deficits and Diagnostic and Therapeutic Strategies for Neurofibromatosis Type 1: Bridging Science and Patient-Centered Care

  https://www.mdpi.com/2411-5150/8/2/31

  Neurofibromatosis type 1 (NF1) is an inherited autosomal dominant disorder primarily affecting children and adolescents characterized by multisystemic clinical manifestations. […] This review provides insight into the spectrum and visual outcomes of NF1, current diagnostic techniques and therapeutic interventions, and explores the influence of NF1-OPGS on visual abnormalities. […] The diagnosis of NF1 primarily relies on clinical criteria established by the National Institutes of Health (NIH) in 1987. […] Thus, children meeting clinical criteria for NF1 are expected to undergo regular eye exams to detect asymptomatic OPGs. […] In terms of vision, Lisch nodules (LNs) serve as pathognomonic markers of NF1, indicating a potential vision-threatening condition. […] Detecting LNs through a slit lamp examination is a straightforward, noninvasive, and cost-effective method for accurately diagnosing NF1.

• #14 Neurofibromatosis Type 1 Diagnosis & Treatment – NYC | Columbia Neurosurgery in New York City

  https://www.neurosurgery.columbia.edu/patient-care/conditions/neurofibromatosis-type-1

  A diagnosis can usually be made in the clinic by acquiring a medical history and performing a physical examination. […] In addition, a neurological examination may be conducted to seek neurofibromas and any brain tumors. […] Imaging studies add detail to physicians understanding of an individual patients neurofibromas and the brain tumors that may accompany NF1. […] To confirm the diagnosis, a tissue biopsy must be performed. […] Although NF1 can usually be diagnosed during a visit with a physician, genetic testing of a blood sample may be helpful for confirmation.

• #15 Diagnosis – Neurofibromatosis Program

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

  Because many features of NF1 are age-related, they are not often present in very young children with the disorder. Many features often appear over time frequently not until late childhood (age 7-10) or adolescence and the onset of puberty. […] 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.

• #16 Neurofibromatosis | Boston Children’s Hospital

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

  Children can have different pathways to a diagnosis of NF1, but a typical diagnostic process might look like this: The pediatrician notices some caf-au-lait spots on the childs skin (these may look to the parent just like birthmarks). These spots may be present at birth, but more commonly they develop through the first few years of life. Since this is one of the diagnostic criteria of NF1, the pediatrician may recommend that the child schedule an evaluation with our Neurofibromatosis Program. […] If your child meets the clinical criteria for diagnosis of NF1 at this time, her doctor will make the diagnosis, and discuss next steps with you. The clinical criteria are that she must have at least two of the following: […] If your child doesnt meet the clinical criteria for diagnosis, her doctor will schedule periodic follow-up visits to see if the symptoms develop. In some cases, the doctor may want to do genetic testing.

• #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). […] When a specific mutation is known, preimplantation genetic diagnosis can also be offered to couples using in vitro fertilization with selection of unaffected embryos for transfer. […] 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.

• #18 A mini review on neurofibromatosis type 1 from the radiological point of view

  https://www.rarediseasesjournal.com/articles/a-mini-review-on-neurofibromatosis-type-1-from-the-radiological-point-of-view.html

  Neurofibromatosis type one (NF1) belongs to the most frequent rare diseases, requiring various methods of diagnostic imaging at different stages of diagnostics and follow-up. […] Various methods of diagnostic imaging are used at different stages of diagnostics and follow-up of many of these manifestations. […] The diagnostic criteria for NF1 were defined in 1997 by the National Institute of Health (NIH) Criteria Consensus Conference and are as follows: – six or more spots of cafe au lait type more than 5 mm in diameter, – two or more neurofibromas or one plexiform neurofibroma, – freckles or skin discolorations in the places inaccessible for light (armpits, groins, pubic region), – two or more Lisch nodules on the iris, – characteristic skeletal changes, – a first-degree relative suffering from NF1. At least two criteria must be met for clinical diagnosis.

• #19 A mini review on neurofibromatosis type 1 from the radiological point of view

  https://www.rarediseasesjournal.com/articles/a-mini-review-on-neurofibromatosis-type-1-from-the-radiological-point-of-view.html

  Radiological features of NF1 in central nervous system are well-known and widely described in the literature and have been in the field of interest of our centre as well as other manifestations of the disease. […] Unidentified neurofibromatosis objects (UNO), formerly called unidentified bright objects (UBO) detected on magnetic resonance imaging (MRI) are typical of NF1. […] MRI is recommended for follow-up of clinically suspected tumours, single whole-body MR is recommended at transition to adulthood. Positron emission tomography/computed tomography is useful for the detection of malignant transformation of tumours in NF1 patients. […] It has been stated in the literature at least 15 years ago by French experts that regular imaging follow-up studies, often required by the clinicians, should not be routinely performed in NF1 patients.

• #20 A mini review on neurofibromatosis type 1 from the radiological point of view

  https://www.rarediseasesjournal.com/articles/a-mini-review-on-neurofibromatosis-type-1-from-the-radiological-point-of-view.html

  It is more reasonable to perform follow-up MRI in cases of new/progressing clinical signs and symptoms. […] The only controversial exception was MRI for early detection of optic pathway gliomas in children but it is not advised any more now. At present MRI is generally recommended for follow-up of clinically suspected tumours, both intra- and extracranial and it is recommended to consider a single whole-body MR examination at transition to adulthood which might assist in determining approaches to long-term follow-up in the future life of a patient.

• #21 Type 1 neurofibromatosis – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/410

  Type 1 neurofibromatosis (NF1) is an autosomal-dominant genetic disorder with the defining features of caf au lait spots, multiple neurofibromas, and iris Lisch nodules. […] Diagnosis is made clinically; RNA-based NF1 mutation molecular testing to confirm the diagnosis is recommended. […] Regular follow-up, especially of complex cases, is recommended to identify early lesions, especially malignant peripheral nerve sheath tumors. […] Key diagnostic factors include family history of NF1, pain in any location, neurologic deficits, compromised vision, and skin manifestations such as caf au lait spots and neurofibromas. […] Genetic testing to confirm NF1 mutation is one of the first tests to order.

• #22 Visual Deficits and Diagnostic and Therapeutic Strategies for Neurofibromatosis Type 1: Bridging Science and Patient-Centered Care

  https://www.mdpi.com/2411-5150/8/2/31

  Advanced imaging techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI), are ideal to visualize the entire optic nerve or the optic pathway. […] However, MRI is the preferred method because of superior soft tissue resolution, since OPGs cannot be easily detected on CT scans. […] Optical coherence tomography (OCT) uses reflected near infrared light to produce cross sectional images of retinal tissue structure with a depth of several hundred microns and can help in the diagnosis and evaluation of OPG-associated pathology. […] In NF1 patients, RGC degeneration can be evaluated by measuring the thickness of the different retinal layers. […] The management of NF1-associated vision impairment requires a multidisciplinary approach, involving close collaboration between ophthalmologists, oncologists, neurologists, geneticists, neurosurgeons, endocrinologists, and pathologists.

• #23 Neurofibromatosis type 1 | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/neurofibromatosis-type-1

  A clinical diagnosis of neurofibromatosis type 1 (NF1) is made when a person has two or more of the following features: […] A detailed review of an individuals medical and family history is important in diagnosing NF1. A doctor or genetic counselor may gather information that indicates which members of the family have developed clinical manifestations of neurofibromatosis type 1 (NF1), such as caf-au-lait spots or neurofibromas. If the pattern of clinical features and/or cancers is suggestive of neurofibromatosis type 1, the physician or counselor may recommend genetic testing. […] In order to confirm on a molecular level that an individual has neurofibromatosis type 1 (NF1), he or she can undergo genetic testing: […] It is estimated that approximately 90 to 95 percent of individuals carrying a clinical diagnosis of NF1 will have a mutation involving the nf1 gene.

• #24 NF1Z – Overview: Neurofibromatosis Type 1, NF1, Full Gene Analysis, Varies

  https://www.mayocliniclabs.com/test-catalog/overview/614585

  Evaluating patients with a personal or family history suggestive of neurofibromatosis type 1 (NF1) […] Establishing a diagnosis of a NF1 allowing for targeted cancer surveillance based on associated risks […] Identifying genetic variants associated with increased risk for NF1 allowing for predictive testing of at-risk family members […] This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in the NF1 gene associated with neurofibromatosis type 1 (NF1). See Method Description for additional details. […] Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, familial screening, and genetic counseling for NF1 […] Clinical Correlations: Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.

• #25 NF1 – genetic testing

  https://www.eviq.org.au/cancer-genetics/adult/genetic-testing-for-heritable-pathogenic-variants/1908-nf1-genetic-testing

  The diagnosis of NF1 is usually based on clinical diagnostic criteria. Genetic testing does not alter the care of individuals meeting the clinical criteria for NF1. It may be useful in confirming the diagnosis in those not meeting the clinical criteria and for informing reproductive planning. […] For individuals with a clinical diagnosis of NF1, genetic testing is not needed to confirm the diagnosis or to inform management. […] A range of testing methodologies are needed to identify pathogenic changes in the NF1 gene including: sequencing (genomic DNA +/- cDNA), copy number analysis, chromosomal microarray analysis if whole NF1 gene deletion or microdeletion suspected. […] If a pathogenic variant is identified, refer to a clinical genetics service or familial cancer centre for review, family risk notification and predictive testing.

• #26 Neurofibromatosis type 1 (NF1): How is it diagnosed?

  https://www.aboutkidshealth.ca/neurofibromatosis-type-1-nf1-how-is-it-diagnosed

  Genetic testing can find mutations (changes) in the NF1 gene. It is done by taking a blood sample. The NF1 gene can be analyzed to see if the person has a normal or a changed copy of the gene. […] A positive test result confirms NF1. If the test is positive, your child has NF1. This means a mutation was found in your child’s NF1 gene. […] A negative test result means a mutation was not found in your child’s NF1 gene. A negative test result does not rule out NF1. About 5% of adults with a clinical diagnosis of NF1 still have negative DNA tests. […] Sometimes, the result of the genetic test is hard to interpret. Not every mutation in the NF1 gene causes neurofibromatosis. It may be unclear whether the mutation is a harmless change or one that will cause the signs of NF1. […] A genetic test can diagnose a young child who does not yet have all the clinical signs of NF1. […] A positive test result cannot predict how mild or severe problems of NF1 may be. A negative test result does not necessarily rule out a diagnosis of NF1.

• #27

  https://link.springer.com/article/10.1007/s00439-021-02410-z

  The presence and number of choroidal anomalies (CA) is age-dependent; their prevalence is lower in children with NF1 than in adults with the disease. […] If CA are present in healthy controls, they represent single lesions. […] Multiple CA are not detected in patients with Legius syndrome and may represent an important distinguishing diagnostic feature. […] The recruitment of genetic testing to make possible a definitive diagnosis of NF1 is particularly important in children and young adults with isolated multiple CALM but without a family history of the disease. […] Genetic testing performed to detect pathogenic NF1 variants may also facilitate the diagnosis in some families with spinal NF1 or patients with the pathogenic in-frame deletion in NF1 exon 17 at position c.2970-2972 delAAT which is associated with typical pigmentary features of NF1, but not with neurofibromas.

• #28 NF1Z – Overview: Neurofibromatosis Type 1, NF1, Full Gene Analysis, Varies

  https://www.mayocliniclabs.com/test-catalog/overview/614585

  If testing was performed because of a clinically significant family history, it is often useful to first test an affected family member. Detection of a reportable variant in an affected family member would allow for more informative testing of at-risk individuals. […] Next-generation sequencing may not detect all types of genomic variants. In rare cases, false-negative or false-positive results may occur. […] This test is not designed to detect low levels of mosaicism or to differentiate between somatic and germline variants. If there is a possibility that any detected variant is somatic, additional testing may be necessary to clarify the significance of results. […] Evaluation and categorization of variants are performed using published American College of Medical Genetics and Genomics and the Association for Molecular Pathology recommendations as a guideline. […] Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.

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

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

  Molecular analysis of the NF1 gene is important in clinical practice to confirm the diagnosis, to differentiate from phenocopies (such as Legius syndrome) and to allow genetic counseling. […] In France, one of the options for preventing the birth of an affected child is prenatal diagnosis (PND) by chorionic villus sampling (CVS) or amniocentesis, with the option to terminate the pregnancy if the fetus is affected. […] 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.

• #30 Neurofibromatosis Type 1 (NF1): Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/14422-neurofibromatosis-type-1-nf1

  A healthcare provider will diagnose neurofibromatosis type 1 after a physical exam and testing. […] Tests may include: Imaging tests, like an MRI, X-ray or CT scan. […] Genetic testing. […] An eye exam. […] For many people, an NF1 diagnosis occurs during adulthood. […] A healthcare provider can help you manage your symptoms. […] There isnt a cure for neurofibromatosis type 1. […] If you have NF1, you should have at least one regular medical check-up every year, along with an annual ophthalmologic (eye) examination. […] You should visit a healthcare provider at least once annually for a check-up to make sure the following NF1-affected parts of your body are functioning as expected: Eyes. […] Nervous system. […] Skin. […] Cardiovascular system. […] Spine. […] If you plan on expanding your family and you have a known history of NF1, talk to your provider about genetic counseling.

• #31 Neurofibromatosis type 1 (NF1)

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

  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.

• #32 Neurofibromatosis – AANS

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

  Children with NF1 should be checked for height, weight, head circumference, evidence of normal sexual development, signs of learning disability and/or behavioral issues. […] Adults with NF1 generally have standard physical evaluations and an examination of the skin for growths, spots, scoliosis, blood pressure, vision and screening for hearing loss. […] Patients with NF2 should have similar routine examinations and care. […] There is no known treatment or cure for neurofibromatosis or schwannomatosis.

• #33 Neurofibromatosis Type 1 (for Parents) | Nemours KidsHealth

  https://kidshealth.org/en/parents/nf.html

  NF1 may be diagnosed before or at birth using genetic (DNA) tests. A doctor usually suggests genetic testing for NF1 if: […] Most children with NF1 are diagnosed only after several caf-au-lait spots appear. A doctor usually will: […] The doctor will do an exam and may work with a team of specialists who diagnose and treat children with NF1, including: […] When doctors suspect a child has NF1, they sometimes look for brain, bone, and other problems using: […] Because children with NF1 get more signs and symptoms as they grow, the diagnosis may not be made right away. Almost all kids with the condition are diagnosed by the time they’re 8 years old.

• #34 Neurofibromatosis Type 1: Diagnostic Timelines in Children | Actas Dermo-Sifiliográficas

  https://www.actasdermo.org/es-translated-article-neurofibromatosis-type-1-articulo-S0001731023000728

  Diagnosis of neurofibromatosis 1 (NF1) diagnosis is challenging in young children without a family history of NF1. […] The aims of this study were to estimate diagnostic delays in children without a family history of NF1 and to examine the effects of considering caf-au-lait macules and skinfold freckling as a single diagnostic criterion. […] We believe that the National Institutes of Health’s diagnostic criteria for NF1 should be updated to aid diagnosis in young children. […] The diagnosis of neurofibromatosis type 1 (NF1) is based on confirmation of at least 2 of the 7 diagnostic criteria established by the National Institutes of Health (NIH) in 1987. […] Although the diagnostic features of NF1 may be easy to recognize in adults, young children without a family history of this disease often have to wait several years before a definitive diagnosis can be made.

• #35 Neurofibromatosis Type 1: Diagnostic Timelines in Children | Actas Dermo-Sifiliográficas

  https://www.actasdermo.org/es-translated-article-neurofibromatosis-type-1-articulo-S0001731023000728

  The diagnostic delay has been estimated at 2 to 3 years, and just 20 to 46% of children without a family history of NF1 are diagnosed before 2 years of age. […] In our series, just 6.48% of patients met the diagnostic criteria for NF1 before this age. […] We agree with Legius et al. that it was necessary to update the NIH diagnostic criteria for NF1.

• #36 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

  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.

• #37 NF1 – genetic testing

  https://www.eviq.org.au/cancer-genetics/adult/genetic-testing-for-heritable-pathogenic-variants/1908-nf1-genetic-testing

  If a variant of uncertain significance is identified, consider referral to a clinical genetics service or familial cancer centre for review and guidance. […] If genetic testing in DNA from peripheral blood does not identify a pathogenic variant, testing of other tumour and tissue samples may be indicated to assess for mosaicism.

• #38 SciELO Brazil – Neurofibromatoses: part 1 – diagnosis and differential diagnosis Neurofibromatoses: part 1 – diagnosis and differential diagnosis

  https://www.scielo.br/j/anp/a/F5LFLc9Zy5yVfmFPNqFB4JN/

  Neurofibromatoses (NF) are a group of genetic multiple tumor growing predisposition diseases: neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis (SCH), which have in common the neural origin of tumors and cutaneous signs. […] In most cases, neurology, psychiatry, dermatology, clinical geneticists, oncology and internal medicine specialists are able to make the differential diagnosis between NF and other diseases and to identify major NF complications. […] Nevertheless, due to its great variability in phenotype expression, progressive course, multiple organs involvement and unpredictable natural evolution, NF often requires the support of neurofibromatoses specialists for proper treatment and genetic counseling. […] This Part 1 offers step-by-step guidelines for NF differential diagnosis.

• #39 New criteria for the diagnosis of type 1 neurofibromatosis and Legius syndrome | UZ Leuven

  https://www.uzleuven.be/en/news/new-criteria-diagnosis-type-1-neurofibromatosis-and-legius-syndrome

  An international team under the supervision of prof. dr. Eric Legius of UZ Leuven has reached a consensus about new criteria for the diagnosis of type 1 neurofibromatosis and the Legius syndrome. […] „In case of suspected type 1 neurofibromatosis or the Legius syndrome it is very important to have a correct diagnosis from an early age to follow and treat patients better.” – prof. dr. Eric Legius, centre for human genetics at UZ Leuven […] Until recently, the American NIH diagnostic criteria were used for NF1. These criteria date from 1987 and don’t allow a distinction between the two disorders, because at that time the Legius syndrome had not been discovered yet. […] It is important to come to a diagnosis at an early age, because NF1 is a lot more serious and requires careful follow-up.

• #40 A Discussion of Revised Diagnostic Criteria Released for NF1 and Legius Syndrome – Neurofibromatosis Program

  https://www.uab.edu/medicine/nfprogram/blog/a-discussion-of-revised-diagnostic-criteria-released-for-nf1-and-legius-syndrome

  Major changes in the new criteria concern the role of genetics and genetic testing. Finding a pathogenic variant in the NF1 gene is now a diagnostic criterion, though this alone is not sufficient to establish a definitive diagnosis unless another criterion is met. […] The revised criterion specifies either the presence of two or more Lisch nodules OR the presence of two or more choroidal abnormalities (CAs). […] For the first time, diagnostic criteria have been established for mosaic NF1, which can produce segmental NF or can result in generalized manifestations. […] Although the original diagnostic criteria formulated in 1987 have proved to be very useful, advances in knowledge of NF1 made this revision timely.

• #41 New criteria for the diagnosis of type 1 neurofibromatosis and Legius syndrome | UZ Leuven

  https://www.uzleuven.be/en/news/new-criteria-diagnosis-type-1-neurofibromatosis-and-legius-syndrome

  However, it is very important to come to a diagnosis at an early age, because NF1 is a lot more serious: the disorder comes with subcutaneous nerve tumours (neurofibromas) that can turn malignant in some cases and require careful follow-up. […] A genetic test is informative, but not required for a NF1 diagnosis. The clinical findings remain important. […] We were able to determine which clinical and genetic criteria are relevant today for the diagnosis of NF1. […] The new diagnostic criteria play an important role in determining which patients will need intensive follow-up and qualify for medication.

• #42 A Discussion of Revised Diagnostic Criteria Released for NF1 and Legius Syndrome – Neurofibromatosis Program

  https://www.uab.edu/medicine/nfprogram/blog/a-discussion-of-revised-diagnostic-criteria-released-for-nf1-and-legius-syndrome

  In May, revised diagnostic criteria for NF1 were published in Genetics in Medicine, the journal of the American College of Medical Genetics and Genomics. The revised criteria are the product of a systematic, multi-year collaborative project of more than 90 NF experts from the international scientific community to arrive at a broad consensus. […] Among the challenges of diagnosing NF1 are that many of the features of the condition are age-dependent, and there is also wide variability in its presentation and expression. […] The methodology used to acquire clinical insight from NF experts for the revised criteria involved a multi-step process that included the Delphi method, which utilized electronic questionnaires to gather information. […] The new diagnostic criteria for NF1 are broadly similar to those released in 1987, although they have been annotated and modified to reflect our expanded knowledge of the condition.

• #43

  https://link.springer.com/article/10.1007/s00439-021-02410-z

  The likelihood that a child with isolated multiple CALM has non-mosaic NF1 is 62-66%. […] Genetic testing is therefore important to confirm the clinical diagnosis and identify at-risk relatives. […] The revised diagnostic criteria for NF1 may facilitate an early diagnosis, particularly in young children with isolated CALM and without a parent with NF1.

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