Neurofibromatosis 1

NF1 Life expectancy 8 years lower than general population Multiple café au lait spots Axillary freckling Multiple cutaneous fibromas Lisch nodules LD in 50% Plexiform neurofibromas Optic nerve gliomas (can lead to blindness) Malignant peripheral nerve sheath tumours (high mortality rate but only occur in 1-3%) Scoliosis Tibial dysplasia Vasculopathy Increased risk of other cancers, including breast cancer Radiotherapy (previously used to treat optic glioma) increases cancer risk - MPNST

Diagnosis: Six or more café au lait macules over 5 mm in greatest diameter in prepubertal individuals and over 15 mm in greatest diameter in postpubertal individuals Two or more neurofibromas of any type or one plexiform neurofibroma  Freckling in the axillary or inguinal regions Optic glioma Two or more Lisch nodules (iris hamartomas) A distinctive osseous lesion such as sphenoid dysplasia or tibial pseudarthrosis A first-degree relative (parent, sib, or offspring) with NF1 as defined by the above criteria  If a child has more than 6 café au lait spots they should be strongly suspected as having NF1 (95% chance) Genetic testing rarely needed

Management:   After diagnosis, the following investigations: Genetics consultation Physical examination of skin, skeleton, cardiovascular system and neurological system Developmental assessment in children  Neurofibromas can be removed surgically (plexiforms difficult to remove in this manner) Pain may indicate peripheral nerve sheath tumour and warrants investigation using MRI >> complete surgical excision Chemotherapy for progressive optic nerve gliomas in children   Surveillance: Annual physical examination Annual ophthalmic investigation Regular Developmental assessment of children Blood pressure monitoring Early breast screening to be considered  

Inheritance: Autosomal Dominant 1 in 2,500 live births Extreme clinical variability within families (need second hit to manifest phenotype) 50% of cases are de novo Mutation in TS gene Neurofibromin Whole gene deletion mutation – more severe phenotype

Clinical features

diagnosis

treatment & surveillance

inheritance