Neurofibromatosis 2 (NF2): Clinical characteristics of 63 affected individuals and clinical evidence for heterogeneity

Abstract

To determine the spectrum of manifestations in neurofibromatosis 2 (NF2) and to assess possible heterogeneity, we evaluated 63 affected individuals from 32 families. Work-up included skin and neurologic examinations, audiometry, a complete ophthalmology examination with slit-lamp biomicroscopy of the lens and fundus, and gadolinium-enhanced MRI of the brain and, in some, of the spine. Mean age-at-onset in 58 individuals was 20.3 years; initial symptoms resulted from vestibular schwannomas (44.4%), other CNS tumors (22.2%), skin tumors (12.7%), and ocular manifestations including cataracts and retinal hamartomas (12.7%). Five asymptomatic individuals were diagnosed through screening. Vestibular schwannomas were documented in 62 individuals (98.4%); other findings included cataracts (81.0%), skin tumors (67.7%), spinal tumors (67.4%), and meningiomas (49.2%). Usually, clinical manifestations and course were similar within families but differed among families. To assess possible heterogeneity, we assigned affected individuals to three proposed subtypes (representing mild, intermediate, and severe NF2) based on age-at-onset, presence or absence of CNS tumors other than vestibular schwannomas, and presence or absence of retinal hamartomas. Comparisons among the three subtypes for many clinical parameters demonstrated that patients in the mild subtype differed from those in the other two subtypes for most parameters, but that none of the parameters distinguished patients in the intermediate subtype from those in the severe subtype. Thus, there are likely two rather than three subtypes of NF2. Classification of patients to subtype may aid in counseling about long-term prognosis and in formulating individualized guidelines for medical surveillance.

Things that go bump in the light. The differential diagnosis of posterior uveal melanomas

“…Since then there have been a number of reports supporting this association. 134,[140][141][142][143][144][145][146][147] It is interesting to note that epiretinal membranes, retinal hamartomas and CHR-RPEs have all been reported in association with NF-2 143 and it is probable that they represent a spectrum of a continuous disease process. 125 …”

Bilateral lower limb paralysis as initial symptom of neurofibromatosis type 2: A case report

“…Children who develop NF2 may exhibit a seriously worse course because of multiple tumors. [3,5] NF2 is a dominantly inherited syndrome caused by mutations of the NF2 gene, which is located on chromosome 22, [6] while most pediatric cases were sporadic [4] as well in the present case: neither the parents nor grandparents showed clinical manifestations of NF2.…”

“…Parry et al reported that 33 (67.4%) of 49 patients who underwent imaging studies had spinal tumors: [3] however, the initial symptoms caused by spinal tumors were recognized only in 13 patients (21%). These include radiating pain accompanied by paresthesia, muscle weakness, atrophy, gait unsteadiness, and inturning of the foot.…”

“…[1,2] Bilateral vestibular schwannomas (VSs) develop in more than 90% of patients with NF2, and approximately half of these patients complain of deafness. [3] Other neurologic lesions, including those involving other cranial nerves, the spinal cords and peripheral nerves, are common lesions in patients with NF2. Cataracts and cutaneous tumors are also known as clinical manifestations of NF2.…”

Horner's syndrome: an atypical presentation in a child with neurofibromatosis type 2

“…Other central nervous tumours may also occur, such as meningeomas of the brain, schwannomas of other cranial nerves, spinal nerve roots, and peripheral nerves and gliomas. 3,4 Various eye manifestations are described in patients with NF2, the most common being cataracts that are described in up to 80%. 5,6 Cataracts often have an early onset and may even be congenital.…”