Fig. 26.1
NF1. Coronal and axial T2-weighted images (a–d) show multiple, asymmetric plexiform neurofibromas of the bilateral brachial plexuses and of bilateral lumbar plexuses. Note the confluent aspect of the tumors along the nervous trunks
26.1.3 Clinical Features
A high clinical interfamilial and intrafamilial variability characterizes NF1 phenotype, and clinical manifestations develop over time. The main clinical characteristics are multiple café-au-lait spots, axillary and inguinal freckling, multiple cutaneous neurofibromas, iris Lisch nodules, and learning disabilities (in at least 50 % of individuals with NF1). Less frequent features include macrocephaly, short stature, and potentially more serious manifestations such as plexiform neurofibromas, optic nerve and other central nervous system gliomas, malignant peripheral nerve sheath tumors, scoliosis, tibial dysplasia, and vasculopathy.
26.1.4 Diagnostic Markers
The diagnosis of NF1 is usually based on clinical findings. Molecular genetic testing of NF1 is available.
Brain and spinal MRIs – Are useful in characterizing tumors, structural abnormalities and the brain, and signs of cerebrovascular disease.
MRI – Is the method of choice for demonstrating the size and extent of plexiform neurofibromas and for monitoring their growth over time.
26.1.5 Top Differential Diagnoses
Legius syndrome, a dominantly inherited disease caused by heterozygous pathogenic mutations of SPRED1, includes multiple café-au-lait spots, axillary freckling, macrocephaly and, in some individuals, facial features that resemble Noonan syndrome, but without Lisch nodules, neurofibromas, and central nervous tumors.
NF1 needs to be differentiated from Neurofibromatosis 2 (OMIM #10100) (see below) that is genetically and clinically distinct from NF1.
Schwannomatosis (OMIM # 162091) (multiple schwannomas of cranial, spinal, or peripheral nerves, usually without vestibular, ocular, or cutaneous features of NF2).
26.1.6 Prognosis
26.1.6.1 Therapy
Complications involving the eye, central or peripheral nervous system, cardiovascular system, spine, or long bones must be referred to a specialist. The treatment of plexiform neurofibromas is empiric, with surgery being the primary option for those lesions that cause a major degree of morbidity. When possible, complete surgical excision of malignant peripheral nerve sheath tumors is required. Chemotherapy of optic gliomas is generally unnecessary as they are usually asymptomatic and clinically stable. Only dystrophic scoliosis often requires surgical management [1, 2].
26.1.6.2 Prognosis
For NF1, a patient’s life expectancy is reduced by 8–15 years. Malignancy (especially malignant peripheral nerve sheath tumors, MPSNT) and vasculopathy are the most important causes of early death in individuals with NF1. Tumors primarily involve the nervous system; for patients with NF1, the prevalence of malignant brain tumors is up to100 times greater than expected up to 50 years of age. Furthermore, the incidence for MPSNT is about 8–13 % among patients with NF1 while 0.001 % in the general population.
26.1.6.3 Disability
Plexiform neurofibromas are the most common and debilitating complications of NF1. They are clinically detected in 27 % of patients, and imaging reveals lesions in about 50 % of individuals with NF1. Plexiform neurofibromas are at risk for malignant transformation in MPNST [1, 2].
Optic glioma, the most common neoplasm in children, detected in about 15 % of patients, is usually asymptomatic and remains so during life, although females are more likely than males to require treatment. The course tends to be more benign than in children without NF1 [3].
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