History
As approximately half of affected persons represent new gene changes, family history is often negative, making diagnosis dependent upon clinical suspicion in adolescents and adults with presenting symptoms such as hearing changes, tinnitus, and balance disturbances. The clinical diagnosis of neurofibromatosis type 2 (NF2) requires that an individual present with at least 1 of the following clinical scenarios: [1]
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Bilateral vestibular schwannomas
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A first degree relative with NF2 AND
Unilateral vestibular schwannoma OR
Any two of: meningioma, schwannoma, glioma, neurofibroma, posterior subcapsular lenticular opacities
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Unilateral vestibular schwannoma AND
Any two of: meningioma, schwannoma, glioma, neurofibroma, posterior subcapsular lenticular opacities
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Multiple meningiomas AND
Unilateral vestibular schwannoma OR
Any two of: schwannoma, glioma, neurofibroma, cataract
In children, especially in the absence of a family history, diagnosis can be more challenging. Ocular or visual problems are common presenting symptoms (41–49%) in children, to include vision impairment or strabismus, while cutaneous features, such as intracutaneous schwannomas and plexiform schwannomas represent another common presenting feature. [19, 20]
There are rare cases, however, in which the clinical diagnosis of NF2 should be reconsidered. This can include the presence of unilateral vestibular schwannoma in the absence of a germline NF2 mutation in which LZTR1-related schwannomatosis should be considered. [21] In addition, bilateral vestibular schwannomas occuring later in life has been reported to occur spontaneously. [22]
Physical Examination
Unlike neurofibromatosis type 1 (NF1), which frequently is associated with a number of cutaneous diagnostic clues, neurofibromatosis type 2 (NF2) is accompanied by few external signs.
Presenting symptoms include hearing loss, ringing in the ears, and balance problems associated with vestibular nerve lesions. Individuals at risk for NF2 should be screened carefully for early signs of hearing loss, motor or sensory changes, and visual deficits.
Optic nerve sheath meningiomas, while generally quite rare in children, may be a presenting sign of NF2. [23]
Cranial nerve palsies may stem from compression of adjacent nerves secondary to an expanding vestibular schwannoma or directly from nonvestibular cranial nerve schwannomas.
Differentiating clinically between the relatively common NF1 and the rare NF2 is occasionally problematic. Patients with NF2 almost never have a large number of cafe-au-lait spots (although in rare cases, 6 or more may be seen), whereas cafe-au-lait spots are numerous and ubiquitous in NF1. Neither axillary nor inguinal freckles are common occurrences in NF2.
Malignant transformation of benign growths is almost unheard of in NF2, unlike in NF1. However, individuals with either NF1 or NF2 can develop multiple subcutaneous lesions that may be clinically indistinguishable (see the images below). In NF2, these lesions most often are defined histologically as schwannomas or neurilemomas, while in NF1 these are defined histologically as neurofibromas. Subcutaneous neurofibromas are occasional findings in NF2.
Subcutaneous and cutaneous lesions in a young man with neurofibromatosis type 2; note paucity of cafe-au-lait spots.
Facial asymmetry, OS proptosis, and exotropia, as well as several subcutaneous lesions on the forehead and face, in a 20-year-old man with neurofibromatosis type 2.
Posterior cervical scar from cord lesion resection, thoracic scoliosis, and subcutaneous masses in a young adult with neurofibromatosis type 2.
Posterior subcapsular lenticular opacities, even in childhood, would be suggestive of NF2, whereas Lisch nodules would be diagnostic of NF1. Finally, although individuals with either NF1 or NF2 can develop dumbbell-shaped spinal cord tumors, schwannomas are common in NF2, whereas neurofibromas are seen primarily in NF1.
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Subcutaneous and cutaneous lesions in a young man with neurofibromatosis type 2; note paucity of cafe-au-lait spots.
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Right neck mass in a patient with neurofibromatosis type 2.
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Facial asymmetry, OS proptosis, and exotropia, as well as several subcutaneous lesions on the forehead and face, in a 20-year-old man with neurofibromatosis type 2.
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Posterior cervical scar from cord lesion resection, thoracic scoliosis, and subcutaneous masses in a young adult with neurofibromatosis type 2.
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Meningioma to the left of midline in a patient with neurofibromatosis type 2.
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Multiple meningiomas (on the left) on the surface of the brain in a patient with neurofibromatosis type 2.
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Bilateral acoustic neuromas in a patient with neurofibromatosis type 2.
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Bilateral acoustic neuromas and a left-sided meningioma in a patient with neurofibromatosis type 2.
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Small ependymoma in a patient with neurofibromatosis type 2.
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Multiple meningiomas in a patient with neurofibromatosis type 2.
