Synopsis
Differentiate NF1, NF2-related schwannomatosis and tuberous sclerosis complex, recognise tumour and seizure emergencies, and organise lifelong multisystem genomic surveillance and targeted treatment.
- NF1 is an autosomal dominant RAS–MAPK tumour-predisposition disorder caused by pathogenic NF1 variants and characterised by café-au-lait macules, flexural freckling, neurofibromas and multisystem complications.
- Plexiform neurofibromas can cause disfigurement, pain and neurological compromise; new persistent pain, rapid growth, hard texture or deficit raises malignant peripheral nerve sheath tumour.
- NF2-related schwannomatosis typically causes bilateral vestibular schwannomas, meningiomas, ependymomas, peripheral nerve tumours and early cataracts rather than the cutaneous neurofibroma burden of NF1.
- Tuberous sclerosis complex arises from TSC1 or TSC2 dysfunction and mTOR activation, producing cortical tubers, subependymal nodules, epilepsy, neuropsychiatric features, skin lesions and renal, lung and cardiac disease.
- Hypomelanotic ash-leaf macules, facial angiofibromas, shagreen patches and ungual fibromas are diagnostic clues in TSC, but a Wood lamp and age-aware examination may be needed.
- Infantile spasms in TSC require urgent EEG and specialist treatment, with vigabatrin favoured in the current NICE epilepsy pathway because delay harms development.
- A subependymal giant-cell astrocytoma can obstruct the foramen of Monro and cause hydrocephalus; new headache, vomiting, visual change or regression needs urgent brain imaging.
- Both conditions require coordinated genetic counselling and organ-specific surveillance; a normal early childhood assessment does not end follow-up because manifestations are age dependent.
Key red flags
Rapid growth, unremitting night pain, hard change or neurological deficit in an NF1 tumour requires urgent assessment for malignant peripheral nerve sheath tumour.
Acute headache, vomiting, papilloedema or declining cognition in TSC may reflect SEGA-related obstructive hydrocephalus and needs emergency imaging.
New or clustered infantile spasms, status epilepticus or developmental regression requires urgent paediatric neurology assessment.
Flank pain, hypotension or falling haemoglobin in TSC raises bleeding renal angiomyolipoma and needs emergency renal and interventional review.
Severe or paroxysmal hypertension in NF1 requires prompt evaluation for renal vascular disease or phaeochromocytoma before routine escalation alone.
Sudden hearing or facial-nerve deterioration in NF2-related schwannomatosis requires expedited neuro-otology and imaging review.
Investigation priorities
Identify the characteristic, age-dependent features and inheritance pattern of NF1, NF2-related schwannomatosis or TSC.
Management branches
A child has multiple café-au-lait macules, flexural freckling or a parent with confirmed NF1.
- Document lesion number, size and distribution and examine skin, eyes, growth, development, spine, limbs, neurology and blood pressure.
- Refer to paediatrics or an NF/genetics service for clinical criteria review and genomic testing where it will clarify diagnosis or family planning.
- Arrange age-appropriate vision, developmental, skeletal and pressure surveillance and educate the family about painful or rapidly changing tumours.
- Avoid routine whole-body imaging unless the specialist pathway indicates it; investigate symptoms and known lesions with the appropriate modality.