Clinical characteristics of neurofibromatosis type 1

Neurofibromatosis type 1 (NF1) is a multisystem neurocutaneous disorder with many clinical manifestations that range widely in severity; it can affect most organs of the body, including the skin, eyes and bony skeleton. Clinical characteristics and their relative frequency are listed in Clinical characteristics of neurofibromatosis type 1. About 40% of people with neurofibromatosis type 1 will have serious medical complications related to the disorder at some time during their life.

Superficial or internal plexiform neurofibromas are tumours that arise in peripheral nerves or at the level of nerve plexuses. Plexiform neurofibromas are congenital, but only half are obvious on clinical examination. Superficial plexiform neurofibromas may cause disfigurement; this is usually evident by the age of 2 years. Internal tumours can compromise function by exerting pressure on nerves or organs. Plexiform neurofibromas can undergo malignant transformation in adults; this may be heralded by rapid growth, pain or a focal neurological deficit.

Optic gliomas may cause decreased visual acuity, hypothalamic dysfunction and precocious puberty. Increased height velocity may be an early sign of precocious puberty. The risk of optic pathway tumours is highest in children younger than 6 years.

There is an increased risk of breast cancer and other types of malignancy in young adults with neurofibromatosis type 1Stewart, 2018 eviQ, 2019 Howell, 2017.

Many adults with neurofibromatosis type 1 experience pain, particularly back pain and headaches. Pain should be investigated for an underlying cause, and to exclude pressure effects from a tumour or malignant transformation.

Table 1. Clinical characteristics of neurofibromatosis type 1
Clinical characteristics	Frequency
changes in skin pigment (cafe-au-lait macules, axillary and inguinal freckling)	cafe-au-lait macules present in 100% of children by age 5 no correlation with severity number increases with age
benign cutaneous and subcutaneous neurofibromas benign iris hamartomas (Lisch nodules)	more than 95% by adulthood
plexiform neurofibromas	occur in 50%
learning disorder	50% will have attention deficit hyperactivity disorder (ADHD), problems with executive function, speech problems and social difficulties that persist into adulthood
optic gliomas	15%; symptomatic in 5 to 7% risk highest in children under 6 years
scoliosis—may be associated with vertebral dysplasia	around 50% increases with age
pain (eg headaches, back pain)	over 50%
anxiety, depression	over 50%
vasculopathy, intracranial tumours, seizures and malignant peripheral nerve sheath tumours (MPNST)	8 to 13% increases with age; onset of malignancy is highest between the ages of 20 and 35 years
hypertension	increases with age
congenital pseudoarthrosis—usually evident once the child is weight-bearing	increases with age
renal artery stenosis	occur in fewer than 5% but cumulatively cause significant mortality
phaeochromocytoma
cardiac abnormalities (eg pulmonary valvular stenosis)