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Year : 2013  |  Volume : 19  |  Issue : 1  |  Page : 36-38

MISME syndrome: A rare clinical entity

Department of Otorhinolaryngology, Head and Neck Surgery, SMHS Hospital, Srinagar, Jammu and Kashmir, India

Date of Web Publication6-Mar-2013

Correspondence Address:
Mirza Aneesa
Department of Otorhinolaryngology, Head and Neck Surgery, SMHS Hospital, GMC Srinagar, Jammu and Kashmir
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0971-7749.108169

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We report a case of a 16 year-old male patient diagnosed as MISME syndrome (MISME: Multiple inherited schwannomas, meningiomas, and ependymomas) which is a rare clinical entity. The disease is autosomally hereditary, without gender predilection and having a clinical penetrance rate of nearly 90%.The gene defect is in chromosome 22 ( NF II gene) and is distinguished from NF I where the gene defect is in chromosome 17.

Keywords: Neurofibromatosis, Schwannoma, Tinnitus

How to cite this article:
Qazi SM, Mehta K S, Aneesa M, Iqbal I. MISME syndrome: A rare clinical entity. Indian J Otol 2013;19:36-8

How to cite this URL:
Qazi SM, Mehta K S, Aneesa M, Iqbal I. MISME syndrome: A rare clinical entity. Indian J Otol [serial online] 2013 [cited 2023 Mar 29];19:36-8. Available from: https://www.indianjotol.org/text.asp?2013/19/1/36/108169

  Introduction Top

Neurofibromatosis type II [NF II or MISME syndrome (multiple inherited schwannomas, meningiomas, and ependymomas)] is an inherited disease. It has an autosomal mode of transmission and incidence of the disease is about 1 in 60,000; it grows at a slow mean rate of approximately 1.2 mm/year. [1] The disease is caused by a genetic defect (mutation or one allele depletion) on the long arm of chromosome 22. This gene encodes a tumor-suppressor protein called Merlin (schwannoma), which is believed to participate at the cell connection of the cytoskeleton with the plasma membrane, thereby influencing the cell's shape, motility, and growth regulation. [2] The disease is autosomally hereditary, without gender predilection. [3],[4] It has a rate of clinical penetrance of nearly 90%. [5]

The three types of tumors that are seen in NF II are schwannomas, meningiomas, and ependymomas, the most common being vestibulocochlear schwannomas found on cranial nerve eight.

  Case Report Top

A 16-year-old male patient presented with a three-year history of mild hearing impairment accompanied by tinnitus on the left side. An audiogram at the first examination showed a mild sensorineural hearing loss on the left side and normal hearing sensitivity on the right side. Brainstem auditory-evoked potentials showed delayed wave V. However, ophthalmological, dermatological, and neurological examinations did not show any pathology. Magnetic resonance imaging (MRI) of the brain showed well-defined mass lesions in relation to both cerebellopontine angles exhibiting isointense signal to gray matter on T1/T2 images and postcontrast enhancement suggesting bilateral (B/L) vestibular schwannoma [Figure 1]. Following this, MRI of spine was indicated which showed an intramedullary contrast-enhancing lesion at C5-7 level, suggesting ependymoma [Figure 2] and multiple contrast-enhancing lesions at T12, L1, and S1, suggesting neurofibromas [Figure 3].
Figure 1: Bilateral vestibular schwannomas

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Figure 2: Ependymoma at C5-C6 level

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Figure 3: Multiple neurofibromas at T12, L1, and S1

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  Discussion Top

NF II is an autosomal dominant disorder associated with B/L vestibular schwannomas. NF II comprises about 5% of all vestibular schwannomas. [6] About half of NF II are sporadic and half of them are dominantly inherited. The gene defect is in chromosome 22 and is called NF II gene which is also a tumor growth-suppressing gene. It is distinguished from NF I where the gene defect is in chromosome 17. [7] NF I is not linked to vestibular schwannomas, except in some rare cases. [8] Both NF I and NF II can present with tumors within the central nervous system (CNS) with somewhat different predilections. Thus, NF II has been combined with meningiomas, fifth cranial nerve gliomas, intramedullary astrocytomas, and spinal neurofibromas. [9],[10]

There are two forms of the NF II. [11] The Wishart phenotype is characterized by multiple cerebral and spinal lesions in patients younger than 20 years with rapid progression, and the Feiling-Gardner phenotype by a single central tumor with slow progression after the age of 20 years. The clinical spectrum of the disease is broad; 90% of the patients show B/L acoustic neuromas, 80% of the patients develop tumors in other cranial nerves or meningiomas, and 50% of the patients develop spinal lesions. The spinal tumors in NF II are classified into two groups, that is, intramedullary lesions called astrocytomas or ependymomas and extramedullary lesions which belong to schwannomas or meningiomas. More than 90% of the affected persons suffer from eye lesions, the most common being juvenile subcapsular cataract.

The diagnostic criteria for NF II are the following:

  • Detection of bilateral acoustic neuroma by imaging procedures
  • First-degree relative with NF II and the occurrence of neurofibroma, meningioma, glioma, or schwannoma
  • First-degree relative with NF II and the occurrence of juvenile posterior subcapsular cataract
The MRI is the most effective technique to detect intracranial structural lesions. It has advantages over computed tomography (CT) and any other type of imaging in the identification of soft tissue lesions, nerve paths, and the presence of tumors. [12],[13] The vestibular schwannoma enhances intensely with contrast medium such as gadolinium and thus virtually all tumors larger than 2 mm, including those in the internal auditory canal (IAC) appear brightly white against black bone or black CSF. [14],[15]

Early diagnosis of a vestibular schwannoma is the key to preventing its serious consequences. Some authors have reported that conservative treatment maybe a choice for patients with few symptoms, small lesions, and who are not able to undergo surgery, due to the slow growth of the tumor. Surgical procedures are the best choice for patients who do not respond favorably to conservative treatment. [16] The prognosis of the vestibular schwannoma surgery is good, although all surgical procedures involve a certain risk of morbidity. [17],[18]

  References Top

1.Yoshimoto Y. Systematic review of the natural history of vestibular schwannoma. J Neurosurg 2005;103:59-63.  Back to cited text no. 1
2.Chen AF, Samy RN, Gantz BJ. Cerebeliopontine angle tumor composed of Schwann and meningeal proliferations. Arch Otolaryngol Head Neck Surg 2001;127:1385-9.  Back to cited text no. 2
3.Hirsch NP. Neurofibromatosis: Clinical presentations and anaesthetic implications. Br J Anaesth 2001;86:555-65.  Back to cited text no. 3
4.Evans DGR, Lye R, Neary W, Black G, Strachan T, Wallace A, et al. Probability of bilateral disease in people presenting with a unilateral vestibular schwannoma. J Neural Neurosurg Psychiatry 1999;66:764-7.  Back to cited text no. 4
5.Palacios E, Valvassori G. Neurofibromatosis 2 (bilateral acoustic neuromas). Ear Nose Throat 1999;178:894.  Back to cited text no. 5
6.Lanser MJ, Sussman SA, Frazer K. Epidemiology, pathogenesis, and genetics of acoustic tumors. Otolaryngol Clin North Am 1992;25:499-520.  Back to cited text no. 6
7.Seizinger BR, Rouleau G, Ozelius LJ, Lane AH, Faryniarz AG, Chao MV, et al. Genetic linkage of von Recklinghausen neurofibromatosis to the nerve growth factor receptor gene. Cell 1987;49:589-94.  Back to cited text no. 7
8.Sadeh M, Martinovits G, Goldhammer Y. Occurrence of both neurofibromatosis 1 and 2 in the same individual with a rapidly progressive course. Neurology 1989;39:282-3.  Back to cited text no. 8
9.Riccardi VM. Von Recklinghausens neurofibromatosis. N Engl J Med 1981;305:1617-27.  Back to cited text no. 9
10.Evans DG, Huson SM, Donnai D, Neary W, Blair V, Newton V, et al. A clinical study of type 2 neurofibromatosis. Q J Med 1998;42:603-18.  Back to cited text no. 10
11.Walter J, Kuhn SA, Brodhun M, Reichart R, Kalff R. "Pulmonary meningioma and neurinoma associated with multiple CNS tumours in a patient with neurofibromatosis type 2". Clin Neurol Neurosurg 2009;111:454-9.  Back to cited text no. 11
12.Karpati R, Loevner L, Cunning D, Yousem D, Li S, Weber R. Synchronous schwannomas of the hypoglossal nerve and cervical sympathetic chain. AJR Am J Roentgenol 1998;171:1505-7.  Back to cited text no. 12
13.Lye RH, Ramsden RT, Stack JP, Gillespie JE. Trigeminal nerve tumor: Comparison of CT and MRI. Case report. J Neurosurg 1987;67:124-7.  Back to cited text no. 13
14.Brackmann DE. Current status of ABR audiometry in acoustic neuroma diagnosis. Arch Otolaryngol Head Neck Surg 1999;125:235.  Back to cited text no. 14
15.Doyle KJ. Is there still a role in auditory brain stem response audiometry in the diagnosis of acoustic neuroma? Arch Otolaryngol Head Neck Surg 1999;125:232-4.  Back to cited text no. 15
16.Walsh RM, Bath AP, Bance ML, Keller A, Tator CH, Rutka JA. The natural history of untreated vestibular schwannomas: Is there a role for conservative management? Rev Laryngol Otol Rhinol 2000;121:21-6.  Back to cited text no. 16
17.Kwiek SJ, Bierzynska-Macyszyn G, Luszawski J, Wlaszczuk P, Lewin-Kowalik J, Wolwender A, et al. Correlation of facial nerve paresis and histopathological type of vestibular schwannoma. Folia Neuropathol 2003;41:237-9.  Back to cited text no. 17
18.McCormick PC, Bello JA, Post KD. Trigeminal Schwannoma: Surgical series of 14 cases with review of the literature. J Neurosurg 1988;69:850-60.  Back to cited text no. 18


  [Figure 1], [Figure 2], [Figure 3]


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