Past names: Reklinghausen disease.
Definition: neurofibromatosis type 1 is an autosomal dominant neurocutaneus disorder. The hallmark features of the disorder are café-au-lait macules and neurofibromas. The diagnostic criteria of the National Institute of Health Consensus Conference in 1987 require 2 or more of the following (1): - >=6 café-au-lait macules:
- >5 mm in prepubertal children
- >15 mm in postpubertal patients
- >=2 any type of neurofibroma or 1 plexiform neurofibroma
- axillary or inguinal freckling
- >=2 Lisch nodules of the iris
- 1 distinct bony lesion
- 1 optic nerve glioma
- 1 first-degree relative with neurofibromatosis type 1
The National Institute of Health criteria are highly sensitive and specific in all age group except in young children <8 years (1).
Variants: - Neurofibromatosis type 1 exhibits complete penetrance, meaning that 100% of patients with the disorder have some phenotypic expression during their lifetimes (1).
- It also demonstrates variable expressivity, meaning that the severity of the condition and the clinical manifestations vary across individuals with the same genotype (1).
- Familial mutations cause approximately half of all cases, and the other half stem from new, spontaneous mutations (2).
Differential diagnosis: - Legius syndrome: also known as neurofibromatosis-1-like syndrome, is an autosomal dominant syndrome caused by a mutation in the SPRED1 gene and is characterized by the presence of café-au-lait macules, axillary freckling, and macrocephaly. Patients with Legius syndrome lack Lisch nodules, neurofibromas, and central nervous system tumors (1).
- Familial multiple café-au-lait spots: autosomal dominant disorder in which patients have many café-au-lait macules without any other symptoms (1).
- Patients with certain homozygous hereditary nonpolyposis colorectal cancer mutations can express multiple café-au-lait macules, axillary freckling, cutaneous neurofibromas, and gastrointestinal malignancy (1).
- a lot more...
Epidemiology: - prevalence: 1 in 3000-4000 individuals in the USA (2).
Symptoms: the typical order of appearance of the most common features is as follows: café-au-lait macules, axillary freckling, Lisch nodules, and neurofibromas (1). - Skeletal findings: neurofibromatosis type 1 may also lead to a gradual degradation of the rib cage, producing flail chest; however, this is uncommon (1).
- Neurologic findings:
- Macrocephaly, a head circumference >=2 standard deviations above the mean, is found in 25-50% of neurofibromatosis-1 patients secondary to increased brain volume (1).
- Peripheral neuropathy as a result of nerve and spinal root compression can occur but is more common in neurofibromatosis type 2 patients (incidence of 3% and 50% respectively) (1).
- Occasionally, patients may have aqueductal stenosis and hydrocephalus (1).
- Vascular findings:
- Neurofibromatosis-1-associated vasculopathies include stenoses, aneurysms, and arteriovenous malformations involving the aortic, renal, mesenteric, carotid-vertebral, subclavian-axillary, iliofemoral, intracerebral, and coronary arteries (3,4).
References: - Perioperative management of neurofibromatosis type 1. The Ochsner Journal. 2012;12:111-121: full text | pdf.
- Neurofibromatosis Fact Sheet from the National Institute of Neurological Disorders and Stroke: link [ accessed April 3rd 2013 ].
- Cardiovascular disease in neurofibromatosis 1: report of the NF1 cardiovascular task force. Genet Med. 2002;4:105–111: full text | pdf.
- Vascular abnormalities in patients with neurofibromatosis syndrome type 1: clinical spectrum, management and results. J Vasc Surg. 2007;46(3):475-484: full text | pdf.
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