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. Additionally, it is also one of the most common inherited CNS disorders, autosomal dominant disorders and inherited tumour syndromes. 1
Individual systemic manifestations are discussed individually:
- central nervous system manifestations of NF1
- musculoskeletal manifestations of NF1
- pulmonary manifestations of NF1
- cutaneous manifestations of NF1
- breast manifestations of NF1
The remainder of this article pertains to a general discussion of neurofibromatosis type 1 (NF1).
Epidemiology
Neurofibromatosis affects 1:2500:2500-3000 individuals 3.
In 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 two or more of following are required 2:
- >6 cafe au lait spots evident during one 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 1NF1 with above criteria
In addition 30~45% (range 30-60%) of patients have learning disabilities.
It is important to consider that NF1 has a much earlier age of onset than schwannomatosis and NF2, with approximately 50% of patients meeting the diagnostic criteria for NF1 by the age of 1 year and approximately 97% meeting the criteria by the age of 8 years 10.
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 features
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
- cutaneous and subcutaneous neurofibromas: benign peripheral nerve sheath tumours
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 dysplasias: especially affecting 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><p>Individual systemic manifestations are discussed individually: </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>. Additionally, it is also one of the most common inherited CNS disorders, autosomal dominant disorders and inherited tumour syndromes. </p><p>Individual systemic manifestations are discussed individually: </p><ul>
-</ul><p>The remainder of this article pertains to a general discussion of neurofibromatosis type 1 (NF1). </p><h4>Epidemiology</h4><p>Neurofibromatosis affects 1:<a href="tel:2500-3000">2500-3000</a> individuals <sup>3</sup>.</p><p>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 two or more of following are required <sup>2</sup>:</p><ul>- +</ul><p>The remainder of this article pertains to a general discussion of neurofibromatosis type 1 (NF1). </p><h4>Epidemiology</h4><p>Neurofibromatosis affects 1:2500-3000 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 two or more of following are required <sup>2</sup>:</p><ul>
-<li>primary relative with NF 1 with above criteria</li>-</ul><p>In addition 30-60% of patients have learning disabilities.</p><p>It is important to consider that NF1 has a much earlier age of onset than schwannomatosis and NF2, with approximately 50% of patients meeting the diagnostic criteria for NF1 by the age of 1 year and approximately 97% meeting the criteria by the age of 8 years <sup>10</sup>. </p><h6>Neoplasms</h6><p>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 <sup>1-6</sup>:</p><ul>- +<li>primary relative with NF1 with above criteria</li>
- +</ul><p>In addition ~45% (range 30-60%) of patients have learning disabilities.</p><p>It is important to consider that NF1 has a much earlier age of onset than schwannomatosis and NF2, with approximately 50% of patients meeting the diagnostic criteria for NF1 by the age of 1 year and approximately 97% meeting the criteria by the age of 8 years <sup>10</sup>. </p><h6>Neoplasms</h6><p>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 <sup>1-6</sup>:</p><ul>