7.2.4 Neurofibromatosis Type 2 (NF2)

7.2.4.1 Introduction

NF2 is also called the neurofibromatosis “central type” because majority of the manifestations are related to the central nervous system. Unlike NF1, cutaneous findings are not a predominant feature of NF2. In contrast, bilateral vestibular schwannoma (VN), also called acoustic neuroma are the hallmark of NF2 (Table 7.4).

7.2.4.2 Historical Context

With the establishment of the NIH diagnostic criteria in 1987 and subsequent genetic studies, it has become evident that NF2 is a distinct clinical entity with minor overlapping features with NF1.

7.2.4.3 Overview with Clinical Significance

NF2 is characterized by central nervous system tumors, and bilateral VN is diagnostic of the disease (Fig. 7.3). The ocular involvement in NF2 is noted in more than two-thirds of cases [36]. The ocular abnormalities seen in NF2 include cataracts, retinal hamartomas, and ocular motility disorders. Ophthalmic features are present in childhood and adolescence and, therefore, are extremely useful in the early diagnosis of NF2 [37].

Fig. 7.3 MRI showing bilateral vestibular schwannoma, a diagnostic finding of NF2. Reproduced with permission from: Singh et al. [228]

Wishart phenotype is characterized by rapid progression of VN that presents in late teens or early twenties. These patients often have intracranial and spinal tumors. Feiling-Gardner phenotype presents later, progresses slowly, and is not associated with other tumors. Lee-Abbott phenotype has variable onset and progression of VN.

7.2.4.5 Genetics

7.2.4.4 Classification

Traditionally, three phenotypes of NF2 based on severity and age of onset of VN have been described. The

Table 7.4 Criteria for definitive diagnosis of neurofibromatosis type 2 [2]

Presence of ONE of the following

Bilateral vestibular schwannoma

The inheritance pattern of NF2 is autosomal dominant with complete penetrance. There is some evidence to suggest that maternally inherited cases have earlier onset than paternally inherited cases [38, 39]. About 50% of the cases represent new mutations [38, 39]. The de novo mutations can occur at prezygotic or postzygotic stages. A postzygotic mutation results in somatic mosaicism, where only a portion of the patient’s cells carries the mutation. It has been estimated that somatic mosaicism may account for 25% of NF2 cases of any subtype among patients with de novo mutation [40]. Patients with somatic mosaicism may display bilateral VNs if the postzygotic mutation occurred early in embryogenesis. If the postzygotic mutation occurred late in development, the patient may display an atypical presentation of NF2 with a unilateral VN and an ipsilateral intracranial tumor, such as a meningioma [41]. Unlike the