Neurofibromatose Typ 1

School ager with hypertension and neurofibromatosis Type 1. Axial CT with contrast of the abdomen shows the aorta to have a normal caliber in the upper abdomen (above left) and a markedly decreased caliber in the mid-abdomen (above right). Sagittal CT (below left) shows a long length of progressive narrowing of the mid-abdominal aorta. 3D CT (below right) shows moderate stenosis of the abdominal aorta from T12 to L2 and severe ostial stenosis of the celiac artery and superior mesenteric artery and the bilateral renal arteries. The inferior mesenteric artery is enlarged with robust collaterals to the celiac and superior mesenteric circulations. There is sparing of the aortic bifurcation and iliac arteries.The diagnosis was midaortic syndrome in a patient with neurofibromatosis Type 1.

School ager

with hypertension and neurofibromatosis Type 1. Axial CT with contrast of the abdomen shows the aorta to have a normal caliber in the upper abdomen (above left) and a markedly decreased caliber in the mid-abdomen (above right). Sagittal CT (below left) shows a long length of progressive narrowing of the mid-abdominal aorta. 3D CT (below right) shows moderate stenosis of the abdominal aorta from T12 to L2 and severe ostial stenosis of the celiac artery and superior mesenteric artery and the bilateral renal arteries. The inferior mesenteric artery is enlarged with robust collaterals to the celiac and superior mesenteric circulations. There is sparing of the aortic bifurcation and iliac arteries.The diagnosis was midaortic syndrome in a patient with neurofibromatosis Type 1.

pediatricimaging.org • CC-by-nc-sa 4.0

Neurofibromatosis type 1 • Neurofibromatosis type 1 - ulnar pseudoarthrosis - Ganzer Fall bei Radiopaedia

Neurofibromatosis

type 1 • Neurofibromatosis type 1 - ulnar pseudoarthrosis - Ganzer Fall bei Radiopaedia

Dixon, A. Neurofibromatosis type 1 - ulnar pseudoarthrosis. Case study, Radiopaedia.org. (accessed on 21 Oct 2022) https://doi.org/10.53347/rID-10282 • CC by-nc-sa 3.0 (modified)

Neurofibromatosis type 1 • Neurofibromatosis type 1 with pedunculated neurofibromas - Ganzer Fall bei Radiopaedia

Neurofibromatosis

type 1 • Neurofibromatosis type 1 with pedunculated neurofibromas - Ganzer Fall bei Radiopaedia

Duarte, C. Neurofibromatosis type 1 with pedunculated neurofibromas. Case study, Radiopaedia.org. (accessed on 21 Oct 2022) https://doi.org/10.53347/rID-43002 • CC by-nc-sa 3.0 (modified)

Neurofibromatosis type 1 • Neurofibromatosis type 1 - Ganzer Fall bei Radiopaedia

Neurofibromatosis

type 1 • Neurofibromatosis type 1 - Ganzer Fall bei Radiopaedia

Jones, J. Neurofibromatosis type 1. Case study, Radiopaedia.org. (accessed on 21 Oct 2022) https://doi.org/10.53347/rID-22541 • CC by-nc-sa 3.0 (modified)

Neurofibromatosis type 1 • Neurofibromata of the foot in von Recklinghausen disease - Ganzer Fall bei Radiopaedia

Neurofibromatosis

type 1 • Neurofibromata of the foot in von Recklinghausen disease - Ganzer Fall bei Radiopaedia

Schubert, R. Neurofibromata of the foot in von Recklinghausen disease. Case study, Radiopaedia.org. (accessed on 21 Oct 2022) https://doi.org/10.53347/rID-15170 • CC by-nc-sa 3.0 (modified)

Neurofibromatosis type 1 • Neurofibromatosis type 1 (extensive) - Ganzer Fall bei Radiopaedia

Neurofibromatosis

type 1 • Neurofibromatosis type 1 (extensive) - Ganzer Fall bei Radiopaedia

Gaillard, F. Neurofibromatosis type 1 (extensive). Case study, Radiopaedia.org. (accessed on 21 Oct 2022) https://doi.org/10.53347/rID-19320 • CC by-nc-sa 3.0 (modified)

Neurofibromatosis type 1 • Neurofibromatosis type 1 - Ganzer Fall bei Radiopaedia

Neurofibromatosis

type 1 • Neurofibromatosis type 1 - Ganzer Fall bei Radiopaedia

Gaillard, F. Neurofibromatosis type 1. Case study, Radiopaedia.org. (accessed on 21 Oct 2022) https://doi.org/10.53347/rID-4136 • CC by-nc-sa 3.0 (modified)

Neurofibromatosis type 1 • Neurofibromatosis - cutaneous neurofibromas - Ganzer Fall bei Radiopaedia

Neurofibromatosis

type 1 • Neurofibromatosis - cutaneous neurofibromas - Ganzer Fall bei Radiopaedia

Singh, G. Neurofibromatosis - cutaneous neurofibromas. Case study, Radiopaedia.org. (accessed on 21 Oct 2022) https://doi.org/10.53347/rID-7332 • CC by-nc-sa 3.0 (modified)

Neurofibromatosis type 1 • Plexiform neurofibromatosis - Ganzer Fall bei Radiopaedia

Neurofibromatosis

type 1 • Plexiform neurofibromatosis - Ganzer Fall bei Radiopaedia

Salam, H. Plexiform neurofibromatosis. Case study, Radiopaedia.org. (accessed on 21 Oct 2022) https://doi.org/10.53347/rID-8265 • CC by-nc-sa 3.0 (modified)

Neurofibromatosis type 1 • Neurofibromatosis type 1 - Ganzer Fall bei Radiopaedia

Neurofibromatosis

type 1 • Neurofibromatosis type 1 - Ganzer Fall bei Radiopaedia

Ibrahim, D. Neurofibromatosis type 1. Case study, Radiopaedia.org. (accessed on 21 Oct 2022) https://doi.org/10.53347/rID-30089 • CC by-nc-sa 3.0 (modified)

Neurofibromatosis type 1 • Neurofibromatosis of breast - Ganzer Fall bei Radiopaedia

Neurofibromatosis

type 1 • Neurofibromatosis of breast - Ganzer Fall bei Radiopaedia

Sambhaji, C. Neurofibromatosis of breast. Case study, Radiopaedia.org. (accessed on 21 Oct 2022) https://doi.org/10.53347/rID-5921 • CC by-nc-sa 3.0 (modified)

Neurofibromatosis type 1 • Neurofibromatosis type 1 - ribbon ribs - Ganzer Fall bei Radiopaedia

Neurofibromatosis

type 1 • Neurofibromatosis type 1 - ribbon ribs - Ganzer Fall bei Radiopaedia

Nemattalla, W. Neurofibromatosis type 1 - ribbon ribs. Case study, Radiopaedia.org. (accessed on 21 Oct 2022) https://doi.org/10.53347/rID-9227 • CC by-nc-sa 3.0 (modified)

Neurofibromatosis type 1 • Plexiform neurofibroma (NF1) - Ganzer Fall bei Radiopaedia

Neurofibromatosis

type 1 • Plexiform neurofibroma (NF1) - Ganzer Fall bei Radiopaedia

Salam, H. Plexiform neurofibroma (NF1). Case study, Radiopaedia.org. (accessed on 21 Oct 2022) https://doi.org/10.53347/rID-7714 • CC by-nc-sa 3.0 (modified)

School ager with hypertension and neurofibromatosis Type 1. 3D reconstruction of a CT angiogram with contrast of the chest and abdomen (left) shows diffuse moderate narrowing of the mid aorta and marked narrowing of the origins of the renal arteries bilaterally. Spectral doppler US of the renal arteries (right) shows parvus tardis waveforms within them bilaterally.The diagnosis was bilateral renal artery stenosis in a patient with neurofibromatosis Type 1.

School ager

with hypertension and neurofibromatosis Type 1. 3D reconstruction of a CT angiogram with contrast of the chest and abdomen (left) shows diffuse moderate narrowing of the mid aorta and marked narrowing of the origins of the renal arteries bilaterally. Spectral doppler US of the renal arteries (right) shows parvus tardis waveforms within them bilaterally.The diagnosis was bilateral renal artery stenosis in a patient with neurofibromatosis Type 1.

pediatricimaging.org • CC-by-nc-sa 4.0

Preschooler with difficulties with vision. Axial (above) and coronal (below) T2 MRI without contrast of the brain shows the left globe is larger than the right globe. The optic nerves bilaterally are thickened and tortuous.The diagnosis was left macrophthalmia and bilateral optic pathway gliomas in a patient with neurofibromatosis type I.

Preschooler

with difficulties with vision. Axial (above) and coronal (below) T2 MRI without contrast of the brain shows the left globe is larger than the right globe. The optic nerves bilaterally are thickened and tortuous.The diagnosis was left macrophthalmia and bilateral optic pathway gliomas in a patient with neurofibromatosis type I.

pediatricimaging.org • CC-by-nc-sa 4.0

School ager with cafe au lait spots and upper back pain. Coronal conventional tomogram of the thoracic spine shows a soft tissue mass in the apex of the right lung causing scalloping of the right side of the upper thoracic vertebral bodies and a scoliosis convex left.The diagnosis was a paraspinal plexiform neurofibroma causing painful scoliosis in a patient with neurofibromatosis Type 1.

School ager

with cafe au lait spots and upper back pain. Coronal conventional tomogram of the thoracic spine shows a soft tissue mass in the apex of the right lung causing scalloping of the right side of the upper thoracic vertebral bodies and a scoliosis convex left.The diagnosis was a paraspinal plexiform neurofibroma causing painful scoliosis in a patient with neurofibromatosis Type 1.

pediatricimaging.org • CC-by-nc-sa 4.0

Neurofibromatosis type 1 • Neurofibromatosis type 1: orbital manifestations - Ganzer Fall bei Radiopaedia

Neurofibromatosis

type 1 • Neurofibromatosis type 1: orbital manifestations - Ganzer Fall bei Radiopaedia

Abdrabou, A. Neurofibromatosis type 1: orbital manifestations. Case study, Radiopaedia.org. (accessed on 21 Oct 2022) https://doi.org/10.53347/rID-49391 • CC by-nc-sa 3.0 (modified)

This image is part of a series which can be scrolled interactively with the mousewheel or mouse dragging. This is done by using Template:Imagestack. The series is found in the category. Orbitadysplasie bei Neurofibromatose Typ 1. MRT - FLAIR axial

This image

is part of a series which can be scrolled interactively with the mousewheel or mouse dragging. This is done by using Template:Imagestack. The series is found in the category. Orbitadysplasie bei Neurofibromatose Typ 1. MRT - FLAIR axial

Wikipedia • CC BY-SA 3.0

Preschooler with cafe au lait spots. AP view of a 3D maximum intensity projection of an MRA of the neck with contrast (above) and AP (below left) and inferior (below right) views of a 3D maximum intensity projection of an MRA of the brain without contrast shows diffuse hypoplasia of the left internal carotid artery. There is stenosis and occlusion of the cavernous and supraclinoid segments of the left internal carotid artery and then there is a thin left M1 segment without evidence of collaterals in the basal ganglia. Additionally, aneurysms are noted in the left A1 and A2 segments.The diagnosis was Moya Moya syndrome in a patient with neurofibromatosis type I.

Preschooler

with cafe au lait spots. AP view of a 3D maximum intensity projection of an MRA of the neck with contrast (above) and AP (below left) and inferior (below right) views of a 3D maximum intensity projection of an MRA of the brain without contrast shows diffuse hypoplasia of the left internal carotid artery. There is stenosis and occlusion of the cavernous and supraclinoid segments of the left internal carotid artery and then there is a thin left M1 segment without evidence of collaterals in the basal ganglia. Additionally, aneurysms are noted in the left A1 and A2 segments.The diagnosis was Moya Moya syndrome in a patient with neurofibromatosis type I.

pediatricimaging.org • CC-by-nc-sa 4.0

Magnetic resonance imaging of sellar and juxtasellar abnormalities in the paediatric population: an imaging review. Glioma in a 2-year-old girl with neurofibromatosis type 1. Sagittal (a) and axial (b) post contrast T1WI shows a partially enhancing lesion enlarging the optic chiasm and proximal optic nerves

Magnetic

resonance imaging of sellar and juxtasellar abnormalities in the paediatric population: an imaging review. Glioma in a 2-year-old girl with neurofibromatosis type 1. Sagittal (a) and axial (b) post contrast T1WI shows a partially enhancing lesion enlarging the optic chiasm and proximal optic nerves

insightsimaging.springeropen.com • Open Access

Imaging of congenital lung diseases presenting in the adulthood: a pictorial review. A 32-year-old man with neurofibromatosis type 1. Coronal (a) reconstruction CT image in the lung window shows lung cysts (white arrows). Cutaneous neurofibroma (blue arrow) and neurofibroma arising from the intercostal nerve (red arrow) are seen on the coronal reconstruction image in the mediastinal window (b)

Imaging of

congenital lung diseases presenting in the adulthood: a pictorial review. A 32-year-old man with neurofibromatosis type 1. Coronal (a) reconstruction CT image in the lung window shows lung cysts (white arrows). Cutaneous neurofibroma (blue arrow) and neurofibroma arising from the intercostal nerve (red arrow) are seen on the coronal reconstruction image in the mediastinal window (b)

insightsimaging.springeropen.com • CC-by-4.0

Imaging of parotid anomalies in infants and children. Neurofibroma, in a child with neurofibromatosis type 1. Frontal and axial T2-weighted images (a and b). Tumor infiltrating the left parotid gland and surrounding spaces. The NF is globally hyperintense (myxoid tissue), with multiple central hyposignals (collagen fibers): “target sign” [white arrow]

Imaging of

parotid anomalies in infants and children. Neurofibroma, in a child with neurofibromatosis type 1. Frontal and axial T2-weighted images (a and b). Tumor infiltrating the left parotid gland and surrounding spaces. The NF is globally hyperintense (myxoid tissue), with multiple central hyposignals (collagen fibers): “target sign” [white arrow]

insightsimaging.springeropen.com • CC-by-4.0

Preschooler with seizures. Axial (left) and coronal T1 MRI with contrast of the orbits shows marked thickening of the optic nerves bilaterally.The diagnosis was bilateral optic pathway gliomas in a patient with neurofibromatosis type I.

Preschooler

with seizures. Axial (left) and coronal T1 MRI with contrast of the orbits shows marked thickening of the optic nerves bilaterally.The diagnosis was bilateral optic pathway gliomas in a patient with neurofibromatosis type I.

pediatricimaging.org • CC-by-nc-sa 4.0

School ager with a rapidly enlarging soft tissue mass of the right chest and armCXR PA and lateral shows a right apical thoracic mass with associated rib thinning that had rapidly increased in size in a short interval. Axial CT without contrast of the chest better defined the right apical mass and demonstrated multiple serpiginous nodules in the soft tissues of the right anterior chest wall.The diagnosis was degeneration of a plexiform neurofibroma into a malignant peripheral nerve sheath tumor in a patient with neurofibromatosis type 1.

School ager

with a rapidly enlarging soft tissue mass of the right chest and armCXR PA and lateral shows a right apical thoracic mass with associated rib thinning that had rapidly increased in size in a short interval. Axial CT without contrast of the chest better defined the right apical mass and demonstrated multiple serpiginous nodules in the soft tissues of the right anterior chest wall.The diagnosis was degeneration of a plexiform neurofibroma into a malignant peripheral nerve sheath tumor in a patient with neurofibromatosis type 1.

pediatricimaging.org • CC-by-nc-sa 4.0

School ager with cafe-au-lait spotsCXR PA shows a large soft tissue mass in the apex of the right lung which causes thinning of the right 1st-5th ribs posteriorly. CT without contrast of the chest shows multiple small nodules throughout the soft tissues of the chest wall.The diagnosis was multiple plexiform neurofibromas in a patient with neurofibromatosis type 1.

School ager

with cafe-au-lait spotsCXR PA shows a large soft tissue mass in the apex of the right lung which causes thinning of the right 1st-5th ribs posteriorly. CT without contrast of the chest shows multiple small nodules throughout the soft tissues of the chest wall.The diagnosis was multiple plexiform neurofibromas in a patient with neurofibromatosis type 1.

pediatricimaging.org • CC-by-nc-sa 4.0

School ager with skin stigmataCXR shows a posterior mediastinal mass. Coronal and sagittal T1 MRI without contrast of the thoracic spine shows dural ectasia.The diagnosis was neurofibromatosis type 1.

School ager

with skin stigmataCXR shows a posterior mediastinal mass. Coronal and sagittal T1 MRI without contrast of the thoracic spine shows dural ectasia.The diagnosis was neurofibromatosis type 1.

pediatricimaging.org • CC-by-nc-sa 4.0

This image is part of a series which can be scrolled interactively with the mousewheel or mouse dragging. This is done by using Template:Imagestack. The series is found in the category Neurofibromatosis type I - orbital dysplasia - MRI - case 001. Orbitadysplasie bei Neurofibromatose Typ 1. MRT - T2w axial

This image

is part of a series which can be scrolled interactively with the mousewheel or mouse dragging. This is done by using Template:Imagestack. The series is found in the category Neurofibromatosis type I - orbital dysplasia - MRI - case 001. Orbitadysplasie bei Neurofibromatose Typ 1. MRT - T2w axial

Wikipedia • CC BY-SA 3.0

Neurofibromatosis type 1 • Neurofibromatosis skin lesions on CXR - Ganzer Fall bei Radiopaedia

Neurofibromatosis

type 1 • Neurofibromatosis skin lesions on CXR - Ganzer Fall bei Radiopaedia

Hacking, C. Neurofibromatosis skin lesions on CXR. Case study, Radiopaedia.org. (accessed on 21 Oct 2022) https://doi.org/10.53347/rID-78725 • CC by-nc-sa 3.0 (modified)

This image is part of a series which can be scrolled interactively with the mousewheel or mouse dragging. This is done by using Template:Imagestack. The series is found in the category Neurofibromatosis type I - orbital dysplasia - MRI - case 001. Orbitadysplasie bei Neurofibromatose Typ 1. MRT - T1w axial

This image

Wikipedia • CC BY-SA 3.0

Radiopaedia • CC-by-nc-sa 3.0 • de

Neurofibromatosis type 1 (NF1), also known as von Recklinghausen disease, is a multisystem neurocutaneous disorder, the most common phakomatosis, and a RASopathy. Additionally, it is also one of the most common inherited CNS disorders, autosomal dominant disorders, and inherited tumor syndromes.

Individual systemic manifestations are discussed individually:

The remainder of this article pertains to a general discussion of neurofibromatosis type 1.

Epidemiology

Neurofibromatosis affects 1:2500-3000 individuals . In half of the cases, the disease is inherited as an autosomal dominant condition. In the other half, the disease is due to a de novo mutation . There is a variable expression but 100% penetrance by 5 years of age .

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 the following are required :

>6 cafe au lait spots evident during one year (prepubertal >0.5 cm, postpubertal >1.5 cm in size)
two or more neurofibromas or one plexiform neurofibroma
optic nerve glioma
distinctive osseous lesion (such as sphenoid wing dysplasia or thinning of long bone cortex with or without pseudoarthrosis)
two or more iris hamartomas (Lisch nodules)
axillary or inguinal freckling
a primary relative with NF1 with above criteria

A mnemonic to help remember these features is CAFE SPOT.

In addition, ~45% (range 30-60%) of patients have learning disabilities, and approximately 1% have hypertension due to renal artery stenosis.

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 .

Neoplasms

It should come as no surprise that a disease due to inactivation of a tumor suppressor gene (see below) is also associated with an increased incidence of numerous tumors :

pheochromocytoma
malignant peripheral nerve sheath tumor (MPNST) ( ~10% of patients)
Wilms tumor
rhabdomyosarcoma
renal angiomyolipoma
glioma
- juvenile pilocytic astrocytoma (~20% of patients)
- optic nerve glioma
- diffuse brainstem glioma
- spinal astrocytoma and spinal pilocytic astrocytoma
carcinoid tumor(s)
leiomyoma(s)
leiomyosarcoma
ganglioglioma
leukemia

Pathology

The NF1 gene locus is on chromosome 17q11.2 and the gene product is neurofibromin, which acts as a tumor suppressor of the Ras/MAPK pathway; inactivation of the gene thus predisposes to tumor development . For this reason, the disorder is classified as a RASopathy .

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 (subcutaneous neurofibroma): localized 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

Breast

neurofibromatosis of the breast

Central nervous system

FASI (focal areas of signal intensity): occur in deep white matter and basal ganglia or corpus callosum , 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 the vertex
moya-moya phenomenon (rare)
buphthalmos

Cutaneous

cutaneous and subcutaneous neurofibromas: benign peripheral nerve sheath tumors

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, gracile bones
multiple non-ossifying fibromas
limb hemihypertrophy

Thoracic

mediastinal masses
- neurofibroma
- lateral thoracic meningocele: typically on the convex side of scoliosis (through widened neural foramina)
- extra-adrenal pheochromocytoma
lung parenchymal disease: ~20%
- diffuse interstitial fibrosis: lower zone
- bullae formation: upper zone
- secondary pulmonary arterial hypertension and cor pulmonale

Vascular

Treatment and prognosis

No single treatment exists, and a combination of supportive and surgical therapies are employed depending on the specific tumors and anomalies present.

Although prognosis is very variable, overall life expectancy is approximately half that of non-affected individuals. Tumors or cardiovascular complications are the most common causes of mortality .

History and etymology

The first name of this condition was Von Recklinghausen disease because, in 1882, von Recklinghausen described cases of neurofibromatosis and recognized it as a nosological entity .

Neurofibromatose Typ 1

Epidemiology

Clinical presentation

Neoplasms

Pathology

Radiographic features

Breast

Central nervous system

Cutaneous

Skeletal

Thoracic

Vascular

Treatment and prognosis

History and etymology

See also

Siehe auch:

und weiter: