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HomemiophthalmologyNeurofibromatosis Type 1: Reviewing the Diagnostic Criteria

Neurofibromatosis Type 1: Reviewing the Diagnostic Criteria

Increasingly targeted therapeutic approaches to treating Neurofibromatosis type 1 (NF1) offer promise. This makes prompt referral of patients with ocular features of this condition more important than ever before.


NF1 is an inherited multi-system disorder with distinctive clinical features, many of which relate to excessive cell growth. The main ongoing ophthalmic concerns are the presence of an optic pathway tumour (glioma) which may result in significant visual impairment, or an orbital-periorbital plexiform neurofibroma which may also cause visual disability as well as an uncosmetic appearance.

Recent advances in the treatment of these conditions, with newer agents which target the active growth pathways of NF1, will hopefully limit the complications of this disorder. Recognition of the ocular features in NF1 may help make a diagnosis and prompt referral to the appropriate health professionals for ongoing management and treatment as required.

NF1 is a common, if not the most common, autosomal dominant condition, with an estimated prevalence of  1/1,900 –1/3,500 people1

Table 1. Diagnostic criteria for NF1.* Confirmed when two or more of the described features are present. *NIH Criteria. Neurofibromatosis: Conference Statement. Arch Neurol. 1988;45 (5):575–578. doi:10.1001/ archneur.1988.00520290115023

NF1 is a common, if not the most common, autosomal dominant condition, with an estimated prevalence of 1/1,900–1/3,500 people.1 The condition is fully penetrant but with a wide range of expressivity, from mild to severe, even within the same family. It is due to a mutation in the NF1 gene, located on the long arm of chromosome 17 (17q11.2)2-4 and has a high spontaneous mutation rate of around 50%.5 Alterations in the gene range from single nucleotide substitutions (point mutations) to larger deletions, sometimes involving the whole gene and resulting in more widespread effects, including developmental delay.

Figure 1. Café au lait spots.

The NF1 gene is known to be a tumoursuppressor gene, encoding the protein neurofibromin which is expressed in neurons and glial tissue, and has an important role in regulating cell growth. Neurofibromin binds to the oncogene Ras (rat sarcoma viral oncogene homolog), switching Ras to its inactive form, thereby controlling cellular proliferation.

Loss of function of neurofibromin, due to mutations in the NF1 gene, allows for an increase in RAS signalling activity, resulting in activation of downstream pathways such as mitogenactivated protein kinase (MAPK) and mammalian target of rapamycin (mTOR), which leads to increased cellular proliferation and unopposed cell growth.7 These pathways play an important role in NF1.

NF1 is a neurocutaneous disorder with involvement in tissues primarily derived from the embryological neural crest. The diagnosis is generally made clinically with the National Institutes of Health (NIH) diagnostic criteria for NF1,8 which requires two or more of the features outlined in Table 1. Using the NIH diagnostic criteria, almost all children with NF1 (97%) will be diagnosed by eight-years-of-age.9 The diagnosis can be confirmed with DNA testing of the NF1 gene. Despite the fact that it is a large gene with no identifiable hot spots, pathogenic variants in the NF1 gene can also be identified in around 95% of individuals with NF1.10

Including the clinical manifestations outlined in the NIH diagnostic criteria, there are many features of NF1, particularly involving cutaneous, ophthalmic and neurological systems, as outlined below.

Figure 2. Axillary freckling.


Café Au Lait Spots 

The typical presentation of a child with NF1 is the appearance of café au lait spots (pigmented macules) on the skin (Figure 1). These may be recognised at birth but generally increase in number in the early years. One study showed that 99% of NF1 patients have six or more café au lait spots by one-year-of-age.9

Skin Fold Freckling 

Multiple small freckles may be noted in intertriginous areas, particularly the axilla (Figure 2) or inguinal regions, but can also occur in the neck, and under the breasts in women. It is estimated that 90% of children with NF1 will show freckling by seven-years-of-age.

Figure 3. ‘S’ shaped plexiform neurofibroma, right upper lid.


As the name of the condition implies, neurofibromas are a hallmark feature of NF1. These can be discrete cutaneous or subcutaneous nodules, which typically appear in adolescence and increase in number throughout adulthood. Neurofibromas arise from the sheaths of small peripheral nerves and are primarily derived from Schwann cells, with a mixture of fibroblasts, macrophages and mast cells.7

Figure 4. Orbital-periorbital plexiform neurofibroma, right side.

However, a more diffuse tumour, called plexiform neurofibroma (PN) has a complex branching arrangement involving multiple nerve bundles, and may occur at birth or present in infancy. The nerves are hypertrophied and tortuous, and often described as feeling like a ‘bag of worms’ on palpation, with infiltration of the surrounding soft tissues.

Figures 5 A and B. Initial axial and coronal views of right orbital-periorbital plexiform neurofibroma of patient in Figure 4.

Around 50% of NF1 individuals will develop a PN.1,10

Other Skin Lesions 

Less common cutaneous manifestations in NF1 include juvenile granuloma (JXG) and anaemic naevi.11


Ocular features generally occur early in NF1 and emphasise the importance of ongoing ophthalmic monitoring. The main ophthalmic manifestations are:

Orbital-Periorbital Plexiform Neurofibroma 

Figures 5C and D. Reduction in size of right orbital-periorbital plexiform neurofibroma of the same patient, following treatment with trametinib.

PNs have a predisposition to occur in the eyelid or orbit and may be visible at birth or soon after. When a PN primarily involves the upper lid, it often gives a characteristic ‘S’ shape (Figure 3), and there is an increased risk of glaucoma. Sometimes growth of a PN can be slow, but they can also be associated with rapid growth, particularly in the first decade, leading to an uncosmetic appearance and disfigurement with increasing soft tissue, orbital overgrowth and facial hemihypertophy/ regional gigantism (Figure 4).

Table 2. Age and percentage of Lisch nodules in NF1.
*To the nearest 5%. Ongoing study at The Children’s Hospital at Westmead.

The triad of a plexiform neurofibroma of the lid, facial hemihypertrophy and glaucoma is characteristic of NF1 and termed Francois syndrome.12 Hyperpigmentation and increased hair growth may also occur, overlying a plexiform neurofibroma.

Amblyopia may result from ptosis causing form deprivation or anisometropia.

Treatment of Plexiform Neurofibroma 

Attempts at surgical excision are generally unsatisfactory due to infiltration of the PN into surrounding normal tissues. Additionally, as the signal for excessive growth remains active, there is a tendency for the PN to recur following surgery.

Due to this lack of regulation of cellular growth, secondary to a mutation in the NF1 gene, more targeted biological treatments directed at inhibiting the downstream growth pathways may arrest cellular proliferation. A key element of the MAPK pathway is MEK, and MEK inhibitors have been developed, initially as anti-cancer drugs. MEK inhibitors, including selumetinib and trametinib, have been shown to be highly effective in inhibiting PN growth, and represent a major breakthrough in treatment of these tumours. While MEK inhibitor therapy will not eliminate a PN, and longterm or even indefinite treatment is required, the drugs show exciting results in tumour stabilisation or shrinkage, with significant improvements in terms of pain, degree of organ compression, and cosmesis (Figure 5).

Lisch Nodules 

Figure 6. Lisch nodules on (A) A blue iris, and (B) A brown iris. (C) Iris mammillations.

Lisch nodules (LN) are melanocytic hamartomas, consisting of a condensation of spindle cells on the anterior iris stroma, with the more pigmented nodules having, in addition, an underlying iris stromal naevus.13 They appear as small elevated dome shaped nodules on the iris, although initially they may be faint and somewhat translucent. In an adult, there are typically around 20–40 LNs of various sizes in each eye (Figure 6A). In a light-coloured eye, they generally appear as orange-tan lesions, whereas in a dark iris, they are often creamy coloured, more irregular in shape and much fewer in number (Figure 6B). They are differentiated from iris mammillations, which are small chocolate brown lesions, uniform in size, particularly seen around the pupillary margins and mainly in darkly pigmented eyes or in ocular melanosis (Figure 6C).

LNs are aged-related, so their absence in a young child does not negate a diagnosis of NF1, as they may develop with time. In an ongoing study of over 360 patients at the Children’s Hospital at Westmead, Sydney (CHW), less than 10% of children who have NF1 will show LNs before twoyears- of-age. Throughout childhood, the incidence goes up around 10% for each year of life thereafter (Table 2).

Figure 7. Bilateral optic nerve and chiasmal glioma.

While LNs are a highly significant diagnostic sign, similar to café au lait spots, they have no morbidity, nor do they correlate with severity of the disease.

Optic Pathway Glioma 

Unfortunately, gliomas involving the visual pathway do have a morbidity because they can interfere with visual function. However, in the context of NF1, optic pathway gliomas convey a better prognosis than in a child who does not have NF1.14-16 The vast majority of NF1 gliomas are classified as World Health Organisation (WHO) grade 1 astrocytomas.17 Gliomas can occur anywhere in the visual pathway, either involving one or both optic nerves, the chiasm, optic tracts or radiations. Post chiasmal involvement is thought to be associated with a poorer prognosis for vision.16,18

It is generally estimated that optic pathway gliomas (OPGs) occur in 15-20% of children with NF1.19-21 However, in a retrospective study at CHW, of 851 children with NF1, the incidence of OPG was only 6.6%.22 The differences in the incidence rates may partly reflect whether routine screening, i.e. magnetic resonance imaging (MRI) is carried out.

Some studies have shown a preponderance of girls who develop OPGs in the context of NF1, with girls more likely to require treatment for visual deterioration than boys.15,18,21

Figure 8. ‘Pseudo-CSF’ sign in bilateral optic nerve glioma.

The suggestion of an OPG may be suspected by a change in vision, or the appearance on fundoscopy of optic atrophy, or much less commonly, disc oedema. Proptosis may be present if the glioma is primarily orbital in origin. Less commonly, strabismus or nystagmus may occur.

When the optic nerves are involved, findings on neuroimaging typically show fusiform enlargement of one or both optic nerves, often with tortuosity and kinking (Figure 7). On T2 weighted imaging, a high intensity signal may be seen surrounding a central core of low intensity signal. This is referred to as the ‘pseudo cerebrospinal fluid (CSF)’ sign, which is considered characteristic of NF1 gliomas23 (Figure 8). It is thought that the perineural tumour produces a mucin-like material within the nerve sheath (perineural arachnoidal gliomatosis) which surrounds the low intensity signal of the optic nerve.23,24 

The presence of two individual optic nerve tumours without any continuous involvement of the chiasm is considered pathognomonic of NF1, in view of the underlying predisposition due to a germline mutation. Frequently however, the glioma involves the chiasm and extends forward into one or both optic nerves, or posteriorly to the optic tracts, and less commonly, optic radiations. Hypothalamic involvement may also occur, which may lead to endocrine abnormalities, such as precocious puberty. Visual field changes, including bitemporal hemianopia, or variations thereof, may also be evident with chiasmal involvement.

OPGs may be indolent and remain stable for many years or may slowly increase in size on serial MRIs. Spontaneous regression has also been reported.22,25 

Figure 9. Choroidal nodules in NF1: right and left eyes.

The policy at CHW is only to scan if there is the suspicion of an OPG, such as a change in vision, or the presence of disc pallor (which may be subtle), or for monitoring of a known glioma. Our previous study at CHW showed that children with asymptomatic tumours (i.e. incidentally detected on a scan performed for other reasons) generally had good visual outcomes, whereas children who presented with symptoms, such as reduced vision or optic disc pallor, often had poorer visual outcomes (Table 3). This validates our protocol to only scan those children in whom the suspicion of an OPG has been raised.

OPG is a childhood disease. The CHW study showed that in children with NF1 and OPG, two thirds will present by six years- of-age, whereas one third of children will present after six years.22 There is little evidence in the literature of a new OPG, or a previously detected OPG becoming activated in adults where regular eye examinations have been performed in childhood. When an optic pathway glioma has been reported to be initially detected in adulthood,26 this is without previous neuroimaging and hence the glioma is likely to have been longstanding. Hence, monitoring for OPG is important in childhood, but not ongoing for adults.

Table 3. Visual outcomes in symptomatic vs. asymptomatic NF1 children with OPG*.
*Thiagalalingham et al, Ophthalmology 2004; 111:568-577. †Mean age of diagnosis.

Schedules for monitoring vary, but presently at CHW a child with NF1 but no known glioma is seen six-monthly until they reach six-years-of-age, then yearly until they are sixteen. However, if an OPG has been detected, then three-monthly ophthalmic assessments and MRIs are carried out over the first one to two years, but this will extend to increasing intervals if the glioma is stable. Regular three-monthly scans and eye assessments continue if the child is undergoing treatment.

Treatment of Optic Pathway Glioma 

At present, indications for treatment of OPGs are a change in visual acuity or evidence of significant progression of the tumour on neuroimaging. Treatment consists of chemotherapy agents, typically with a carboplatin-based regimen, often incorporating vincristine as a second agent. OPGs in NF1 are often a chronic disease, sometimes requiring multiple programs of therapy over several years before becoming quiescent. Second line regimens, such as vinblastine and other cytotoxic drugs, may be needed. More recently the MEK inhibitors have emerged as active agents in treatment of OPGs. Selumetinib, trametinib and others have been used following failure of conventional chemotherapy, but trials are underway exploring their potential use as initial therapy. As oral agents, the MEK inhibitors are simpler to give, and lack typical side effects of cytotoxic chemotherapies; however dermatologic problems are frequent. Radiotherapy has been used in the past but is no longer given in view of the fact that the NF1 gene is a tumour suppressor gene, with a substantial risk of secondary tumours developing following radiotherapy, as well as an increased risk of occlusive vasculopathy.5,19 

Figure 10. Focal areas of increased intensity (FASI) in the brain.

A large retrospective study involving 115 children with NF1-OPG from 10 different sites reported that at completion of chemotherapy, the visual acuity improved in 32% of subjects, remained stable in 40%, and deteriorated in 28%.20 However, further visual deterioration after a period of stability following chemotherapy has been reported with longer follow-up.22,27,28 

Currently, CHW is part of an international multicentre study looking at the natural history of OPGs in the context of NF1, to develop evidenced-based criteria as to when intervention is required, and what are the most effective therapies.

Choroidal Nodules

This is a relatively new sign of NF1 and may rival LNs for diagnostic importance. Choroidal nodules are not seen on fundoscopy, nor with fluorescein angiography or autofluorescence, and require enhanced depth imaging with optical coherence tomography (OCT) or near-infrared reflectance imaging to be seen. Multiple bright white spots are noted in the choroid, particularly around the posterior poles (Figure 9), but can occur anywhere in the fundus. Histologically they have been documented to consist of concentric rings of Schwann cell proliferation surrounding an axon to give an onion-like appearance.29 While not unique to NF1, they are otherwise rare in non-NF1 individuals.

Similar to Lisch nodules, choroidal nodules have a tendency to increase in number with age, and also do not interfere with visual function. They are proving to be a valuable diagnostic marker of NFI, with one study showing that choroid nodules were more frequent in NF1 children than LNs.30 

Choroidal naevi, which are visible on fundoscopy, are also said to occur in NF1 more frequently than in the general population.31 

Figure 11. MR angiography showing marked narrowing of the long segment of the right internal carotid artery (single arrow) with surrounding collateral vessels (dashed arrow) compared with a normal left internal
carotid artery (double arrows).


It is estimated that glaucoma occurs in 1-2% of NF1 patients5 and is typically seen in the context of Francois syndrome. Uncontrolled proliferation of corneal endothelial cells growing across the angle and trabecular meshwork occurs and may be the main cause of glaucoma in NF1, resulting in the congenital ectropion uveae which is frequently present.32,33 Other contributing factors to glaucoma include diffuse infiltration of the anterior chamber angle and ciliary body by neurofibromatosis tissue, excessive pigment deposition in the angle, secondary angle closure due to mechanical obstruction of ciliary body and choroidal neurofibromas, or developmental anomalies of the angle.33,34 Due to the above factors, the glaucoma is often severe and difficult to treat.


Retinal involvement is uncommon and may include retinal hamartomas or retinal vascular abnormalities.


Visual Acuity 

In very young children, quantitative assessments using forced preferential looking techniques, such as Teller Acuity Cards and Cardiff Cards, are preferred to fixation patterns. In preschool children, matching letter techniques, e.g. HOTV or Lea symbols, can be used until the child is old enough to be able to read the Snellen chart.

Figure 12. Hypoplasia of the greater wing of the
sphenoid bone, right side.

Visual Fields 

Visual fields are not generally seen as a reliable measure of visual function, in view of the difficulties in performing perimetry in young children, due to fatigue, or a lack of understanding and concentration. Additionally, there is a significant learning curve in the ability to perform the test, with many false positives, negatives, fixation errors and poor repeatability, thereby limiting its usefulness.

Optical Coherence Tomography 

Evaluation of the retinal nerve fibre layer thickness with serial OCTs provides a valuable objective assessment of whether the optic nerve is thinning and becoming atrophic due to progression of a glioma and correlates well with visual acuity, although when the average retinal nerve fibre layer is less than 60μm, results are difficult to interpret with regard to any meaningful change. As the test requires a considerable degree of cooperation, it is generally limited to older children.

Visual Evoked Potentials 

Assessing optic nerve function with serial electrophysiology, such as pattern or multifocal visual evoked potentials is sometimes used to monitor any progression, although tends not to be sensitive or specific enough, and generally requires a referral to a tertiary hospital setting to be performed.

In Summary 

Serial visual acuity testing still appears to be the most reliable visual function assessment in determining whether treatment of an OPG is required, and the primary outcome measure for ongoing monitoring and effect of treatment.5,19,35 It is also noted that children who have normal vision when first diagnosed with an OPG tend to retain good vision at long term follow-up.16


Peripheral Nervous System 

Figure 13. Herniation of the temporal lobe with increased CSF (arachnoid cyst) into the right orbit due to sphenoid wing hypoplasia and associated with an orbital plexiform neurofibroma.

As previously mentioned, involvement can occur in the peripheral nervous system (PNS) with discrete cutaneous and subcutaneous nodules of individual nerves, or the more complex plexiform neurofibromas. Malignant change most typically occurs in a plexiform neurofibroma and this is usually in the form of a malignant peripheral nerve sheath tumour (MPNST), which has a high mortality and a low five-year survival rate. It is estimated that there is an 8-13% lifetime risk of malignant transformation.7

Central Nervous System 

Gliomas of the visual pathway, hypothalamus, or other parts of the brain and brainstem, as well as the spinal cord are the typical central nervous system (CNS) lesions of NF1.

Hydrocephalus may occur rarely, either by direct compression of the third ventricle with subsequent aqueductal stenosis due to extension of a hypothalamic/chiasmal glioma, or structural anomalies involving the aqueduct. In this context, papilloedema and nystagmus typically occur.

Focal Areas of Signal Intensity 

Focal areas of signal intensity (FASI) are patchy areas of increased signal intensity seen on imaging of the brain on T2 weighted images (Figure 10). They can occur anywhere in the brain, but are particularly evident in the basal ganglia, brainstem and cerebellum.9 They were previously described as ‘unidentified bright objects’ (UBOs), but are now more generally known as FASIs.36 

FASIs most likely represent areas of gliosis, or altered myelination, and tend to disappear in adulthood. They are so frequently seen in young patients with NF1 as to be considered pathognomonic of the condition.

Learning Difficulties and Behavioural Issues 

Learning difficulties and cognitive impairment are commonly seen in NF1 as well as speech delay. There is also an increased risk of attention deficit/ hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Sleep disturbances are also reported more frequently.1,7

Cerebral Vascular Dysplasia/Moyamoya 

Stenosis and occlusion of the major cerebral vessels may occur, particularly the internal carotid and middle cerebral arteries, due to the proliferation of Schwann cells lining the arteries, leading to the possibility of significant morbidity and mortality caused by stroke. However, small collateral vessels may form around the site of occlusion, resembling the appearance of a ‘puff of smoke’ on angiography, termed ‘moyamoya’ in Japanese (Figure 11). This is likely to be the reason that a cerebrovascular stenosis is often asymptomatic, particularly in children.37 


Headaches, including migraine, seizures and chronic pain are also more common in NF1.1 Low muscle tone, muscle weakness and fatigue also occur more frequently.


Bony Lesions 

A typical bony lesion is one of the diagnostic criteria of NF1, and includes:

Sphenoid Wing Dysplasia 

Absence or hypoplasia of the greater wing of the sphenoid (Figure 12) allows for herniation of the temporal lobe into the orbit, with subsequent pulsatile proptosis due to overlying CSF pulsations (Figure 13). Sphenoid wing dysplasia is frequently associated with a plexiform neurofibroma of the upper lid.

Dysplasia of the Tibia and Fibula 

This is typically congenital and unilateral, resulting in bowing of the lower leg. Fractures may occur, with poor healing and non-union (pseudoarthrosis).


An occipital bony defect may occasionally be seen.


Scoliosis generally occurs between five and 15 years-of-age and may be associated with dural ectasia, vertebral degenerative changes, and spinal compression from focal spinal cord lesions.1,38 It is estimated that around 10–15 % of NF1 patients have scoliosis.

Macrocephaly and Short Stature 

Macrocephaly is reported in approximately 50% of NF1 individuals, while around one third have short stature.39


Deficient bone mineralisation and generalised osteopenia are more commonly noted in NF1 than in the general population.7,11 


Reduced Life Expectancy 

It is estimated that NF1 is associated with a reduction in life expectancy of around eight to 15 years.1 This is primarily from malignant tumours, such as MPNST, but also because of an increased risk of other tumours.


As the NF1 gene is a tumour suppressor gene, it is not unexpected to have a predisposition to other tumours. Apart from the very significant increased risk of brain tumours (mainly gliomas), breast cancer is more common, particularly in women younger than 40.1 Phaeochromocytoma (a tumour of the adrenal medulla) also occurs more commonly in NF1. Other tumours with a reported higher incidence in NF1 include rhabdomyosarcoma, gastrointestinal stromal tumours (GIST), glomus tumours, leukaemia, and lymphoma.11


Hypertension is common in NF1. Causes include essential hypertension or secondary to renal stenosis, or phaeochromocytoma.

Cerebrovascular involvement, due to dysplasia of the cerebral vessels, is estimated to occur in around 2.5% of NF1 individuals.37 

Cardiovascular changes, such as valvular pulmonary stenosis, congenital heart defects and hypertrophic cardiomyopathy, have also been reported with increased frequency.10 

Mosaic (Segmental) NF1 

When a somatic mutation occurs during embryological development rather than a germline mutation inherited from a parent, a more localised form of NF1 occurs. This is limited to a body segment only, i.e. segmental neurofibromatosis. The condition is therefore not inherited, and occurs much less frequently than generalised NF1.

Neurofibromatosis-Noonan Syndrome 

Some patients with NF1 mutations will also show manifestations of Noonan syndrome, with ophthalmic features of bilateral ptosis, downslanting palperbral fissures and hypertelorism. Systemic features include short stature and congenital heart disease. Mutations in the PTPN11 gene causing Noonan syndrome may be found.10


Legius Syndrome 

With autosomal dominant transmission, café au lait spots and axillary freckling, Legius syndrome may be confused with NF1, particularly in young children as the disorder fulfils the NF1 diagnostic criteria. Macrocephaly, learning difficulties and ADHD, and a Noonan-like phenotype may also be present, further complicating any differentiation from NF1. However, Legius syndrome is due to a mutation in the SPRED1 gene, also a tumour suppressor gene.40 Importantly, neurofibromas and Lisch nodules are absent, and optic pathway gliomas do not occur.

Neurofibromatosis Type 2 

This is a much less common disorder, with an estimated prevalence of 1:50,000,8 and is due to mutations in the NF2 gene, located on chromosome 22 (22q12.2).41,42 Similar to the NF1 gene, NF2 is a tumour suppressor gene and is also inherited in an autosomal dominant pattern. Clinically, the hallmark of the disorder is bilateral vestibular Schwannomas (acoustic neuromas). Schwannomas and neurofibromas may occur in other cranial and peripheral nerves. Meningiomas are also common in NF2. Cutaneous features include café au lait spots, although generally fewer than seen in NF1, and cutaneous nodules (schwannomas or neurofibromas). Typical ocular findings include posterior subcapsular cataracts/ plaques, epiretinal membranes, retinal hamartomas and optic nerve sheath meningiomas. Lisch nodules are not a feature of NF2.


In February this year, the Federal Government announced an AU$8 million dollar investment specifically for NF support and research; $7 million to be within the Medical Research Future Fund (MRFF) and $1 million to the Children’s Tumour Foundation for ongoing support and advocacy for those living with NF. This exciting development may help to expand the research base to further delineate the natural history of NF1, clarify the complex biological processes that drive the disorder, and investigate newer treatments which will help ameliorate the complications of the condition, as well as providing specific support services as required.


NF1 is a complex disorder, due to a mutation in the tumour suppressor NF1 gene, with many ocular and systemic features and definitive diagnostic criteria. In view of the recent recognition of other features frequently associated with NF1, such as choroidal nodules and FASIs, it is now time for a review and expansion of the diagnostic criteria. As there is a wide range of systems involved in NF1, a multidisciplinary approach is required with input from paediatricians, dermatologists, neurologists and neurosurgeons, geneticists, oncologists, radiologists, neuropsychologists, general and orthopaedic surgeons, orthoptists and ophthalmologists. Ocular features are common in NF1 and hence ophthalmologists play an important role in the diagnosis, monitoring and management of patients with NF1. Recent advances with more targeted therapeutic approaches provide hope for the future to reduce the complications of uncontrolled growth as seen with plexiform neurofibromas, and to limit the visual loss from optic pathway gliomas.

To earn CPD points for this article visit mieducation.com.au/neurofibromatosis-type-1-reviewing-thediagnostic-criteria 

The author gratefully acknowledges Dr Geoff McCowage, oncologist, for his contribution regarding the genetics of NF1 and the treatment of optic pathway gliomas and plexiform neurofibromas, and Dr Kristina Prelog, radiologist, for the MRA images (Figure 11). 

Dr Maree Flaherty MBBS (Hons), FRANZCO is a Senior Consultant in paediatric ophthalmology at The Children’s Hospital at Westmead in Sydney and part of a multidisciplinary team caring for many children with NF1. She is also a Clinical Senior Lecturer, Discipline of Ophthalmology, Sydney Medical School, University of Sydney and the Director of the Children’s Eye Centre, a large private paediatric ophthalmology practice in Western Sydney. 


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