Potential NF1 Diagnostic Pathway1

It is recommended that multidisciplinary neurofibromatosis clinics include a lead clinician, named consultants who are experts in their field

NF1 diagnosis Once the diagnosis is considered, referral should be made to any clinician skilled in the diagnosis of NF1, including geneticists, pediatricians, neurologists or dermatologists
NF1 Specialist Center Multidisciplinary team (MDT) approach to treating patient
  • The role of the specialist clinic is to diagnose NF1 in difficult cases, monitor and managecomplex disease, and educate and support the patient and family
  • A neurologist or geneticist is often a decision-maker at adult NF1 Specialist Centers

Patients may be referred to multiple specialties depending on clinical symptoms and manifestations until a definitive diagnosis can be made and confirmed

Neurosurgery
Dermatologist
Ophthalmologist
Plastic Surgery
Geneticist
orthopaedist
Neurologist
Paediatrics
Psychiatrists
Criteria
Description
CALM
≥6 café-au-lait macules >5 mm in greatest diameter in prepubertal individuals and >15 mm in greatest diameter in postpubertal individuals
Neurofibroma
≥2 neurofibromas of any type or one plexiform neurofibroma
Freckling
Freckling in the axillary or inguinal regiona
Ophthalmological
Optic pathway glioma
≥2 iris Lisch nodules identified by slit lamp examination or ≥2 choroidal abnormalities (CAs)
Osseous lesion
A distinctive osseous lesion such as sphenoid dysplasiab, anterolateral bowing of the tibia, or pseudarthrosis of a long bone
Genetic
A heterozygous pathogenic NF1 variant with a variant allele fraction of 50% in apparently normal tissue such as white blood cells
Parent(s)
A child of a parent who meets the diagnostic criteria specified above merits a diagnosis of NF1 if ≥1 of the above criteria are present

aIf only café-au-lait macules and freckling are present, the diagnosis is most likely NF1 but exceptionally the person might have another diagnosis such as Legius syndrome. At least one of the two pigmentary findings (café-au-lait macules or freckling) should be bilateral;  bSphenoid wing dysplasia is not a separate criterion in case of an ipsilateral orbital plexiform neurofibroma.
CALM = café-au-lait macule; NF1 = neurofibromatosis type 1.
Legius E et al. Genet. Med 2021; 23(8):1506-1513.

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  • Ferner RE, Huson SM, Thomas N, Moss C, Willshaw H, Evans DG, Upadhyaya M, Towers R, Gleeson M, Steiger C, Kirby A. Guidelines for the diagnosis and management of individuals with neurofibromatosis 1. Journal of medical genetics. 2007 Feb 1;44(2):81-8.