Neurofibromatosis type 1
Updates to Article Attributes
Neurofibromatosis type 1 (NF1) or von Recklinghausen disease is a multisystem neurocutaneous disorder and the most common phakomatosis 1. Additionally it is also one of the most common inherited CNS disorders, autosomal dominant disorders and inherited tumour syndromes.
Epidemiology
Neurofibromatosis affects 1:2500-3000 individuals 3. In half of cases, the disease is inherited as an autosomal dominant condition. In the other 50% of cases the disease is due to a new mutation 6. There is variable expression but 100% penetrance by 5 years of age 6.
Clinical presentation
As is the case with many phakomatoses, NF1 results in a variety of abnormalities of variable severity. To make the clinical diagnosis you require two or more of following2:
- > 6 cafe au lait spots evident during 1 year
- two or more neurofibromas or one plexiform neurofibroma
- optic nerve glioma
- distinctive osseous lesion
- sphenoid wing dysplasia
- two or more iris hamartomas (Lisch nodules)
- axillary or inguinal freckling
- primary relative with NF 1 with above criteria
In addition 30-60% of patients have learning disabilities.
Neoplasms
It should come as no surprise that a disease due to inactivation of a tumour suppressor gene (see below) is also associated with increased incidence of numerous tumours 1-6:
- pheochromocytoma
-
malignant peripheral nerve sheath tumour (MPNST)
- previously known as neurofibrosarcoma
- overal risk of developing a MPNST is ~10%7
- Wilms tumour
- rhabdomyosarcoma
- renal angiomyolipoma
- glioma
- carcinoid tumour(s)
- leiomyoma(s)
- leiomyosarcoma
- ganglioglioma
- leukaemia
Pathology
The NF1 gene locus is on chromosome 17q11.2 and the gene product is neurofibromin, acts as a tumour suppressor; inactivation of the gene thus predisposes to tumour development 6.
The disease primarily is a hamartomatous disorder that involves the ectoderm and mesoderm. Usually three types of neurofibromas occur in this disorder and are distinguished on the basis of their gross and microscopic appearances.
- localized neurofibroma (cutaneous neurofibroma) - the most common type, is a focal lesion that typically is located in the dermis and subcutis
- diffuse neurofibroma (sub cutaneous neurofibroma) - localised in the subcutis, usually in the head and neck region.
- plexiform neurofibroma - considered pathognomonic if present ; they may be seen in virtually any location but usually occur in the neck, pelvis, and extremities
Radiographic and clinical spectrum
Neurological (CNS)
- FASI: focal areas of signal intensity in deep white matter and basal ganglia or corpus callosum 5 - areas of T2/FLAIR hyperintensity with no contrast enhancement
- optic nerve glioma or optic pathway glioma (may manifest as enlarged optic foramen)
- progressive sphenoid wing dysplasia
- lambdoid suture defects
- dural calcification at vertex
- moya moya phenomenon (rare)
- buphthalmos
Cutaneous
- café au lait spots
- neurofibromas of cutaneous and subcutaneous peripheral nerves and nerve roots
Skeletal
- kyphoscoliosis
- posterior vertebral scalloping
- hypoplastic posterior elements
- enlarged neural foramina
- ribbon rib deformity, rib notching and dysplasia
- dural ectasia
- tibial pseudoarthrosis or less commonly ulnar pseudoarthrosis
- bony dysplasia especially tibia
- severe bowing
- Multiple NOF
- limb hemi hypertrophy
Chest
- mediastinal masses
- neurofibroma
- lateral thoracic meningocoeles : typically on convex side of scoliosis (through widened neural formina)
- extra adrenal pheochromocytoma
- lung parenchymal disease: ~ 20%
- diffuse interstitial fibrosis : lower zone
- bullae formation: upper zone
- secondary pulmonary arterial hypertension and cor pulmonale
Vascular
Breast
Treatment and prognosis
No single treatment exists, and a combination of supportive and surgical therapies are employed depending on the specific tumours and anomalies present.
Although prognosis is very variable, overall patients with neurofibromatosis type I have a life expectancy approximately half that of non affected individuals, usually succumbing to tumours or cardiovascular complications 8.
See also
-<p><strong>Neurofibromatosis type 1 (NF1)</strong> or <strong>von Recklinghausen disease</strong> is a multisystem neurocutaneous disorder and the most common <a href="/articles/phakomatoses">phakomatosis </a><sup>1</sup>. Additionally it is also one of the most common inherited CNS disorders, autosomal dominant disorders and inherited tumour syndromes. </p><h4>Epidemiology</h4><p>Neurofibromatosis affects 1:<a href="tel:2500-3000">2500-3000</a> individuals <sup>3</sup>. In half of cases, the disease is inherited as an autosomal dominant condition. In the other 50% of cases the disease is due to a new mutation <sup>6</sup>. There is variable expression but 100% penetrance by 5 years of age <sup>6</sup>.</p><h4>Clinical presentation</h4><p>As is the case with many phakomatoses, NF1 results in a variety of abnormalities of variable severity. To make the clinical diagnosis you require two or more of following<sup>2</sup>:</p><ul>- +<p><strong>Neurofibromatosis type 1 (NF1)</strong> or <strong>von Recklinghausen disease</strong> is a multisystem neurocutaneous disorder and the most common <a href="/articles/phakomatoses">phakomatosis</a> <sup>1</sup>. Additionally it is also one of the most common inherited CNS disorders, autosomal dominant disorders and inherited tumour syndromes. </p><h4>Epidemiology</h4><p>Neurofibromatosis affects 1:<a href="tel:2500-3000">2500-3000</a> individuals <sup>3</sup>. In half of cases, the disease is inherited as an autosomal dominant condition. In the other 50% of cases the disease is due to a new mutation <sup>6</sup>. There is variable expression but 100% penetrance by 5 years of age <sup>6</sup>.</p><h4>Clinical presentation</h4><p>As is the case with many phakomatoses, NF1 results in a variety of abnormalities of variable severity. To make the clinical diagnosis you require two or more of following <sup>2</sup>:</p><ul>
-<li>overal risk of developing a MPNST is ~10%<sup>7</sup>- +<li>overal risk of developing a MPNST is ~10% <sup>7</sup>
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