Otology & Neurotology 35:e253Ye255 Ó 2014, Otology & Neurotology, Inc.
Imaging Case of the Month
Bilateral Otospongiosis and a Unilateral Vestibular Schwannoma in a Patient With Myhre Syndrome *Christoph Kenis, †Margriet Verstreken, *Katrien Gieraerts, ‡Bert De Foer, §Nathalie Van der Aa, †Erwin F. Offeciers, and *‡Jan W. Casselman *Department of Radiology, Sint-Jan Hospital, Bruges; ÞEuropean Institute for ORL, and þDepartment of Radiology, Sint-Augustinus Hospital, Wilrijk; and §Department of Medical Genetics, University and University Hospital Antwerp, Edegem, Belgium
Myhre syndrome is a rare disorder characterized by facial dysmorphism, short stature, generalized muscle hypertrophy, skeletal anomalies, and limited joint mobility (1). Hearing loss is frequently reported. The clinical findings have been described in 22 cases till date, and recently, a de novo dominant mutation in the SMAD4 gene was discovered in 19 patients (2). We report a case of Myhre syndrome with bilateral mixed hearing loss and bilateral fenestral otospongiosis on cone-beam computed tomography (CBCT). Magnetic resonance imaging (MRI) also revealed a nodule in the right internal auditory canal (IAC) compatible with a vestibular schwannoma (VS). No high resolution images of the temporal bone in patients with Myhre syndrome have been published, to the best of our knowledge.
membrane (TM) and normally aerated middle ear on the left side. The right TM was sclerotic with normal middle ear aeration assumed. Audiometry showed bilateral severe mixed hearing loss (air conduction: pure tone average (PTA) (0.5-1-2 kHz) = 105 dBHL right ear, 107 dBHL left ear; bone conduction: PTA (0.5-1-2kHz) = 67 dBHL right ear, 70 dBHL left ear). There were absent stapedius muscle reflexes on tympanometry, and the tympanogram showed a flat curve (type B) bilaterally. CBCT allows a better definition of small structures compared with conventional multislice CT scanners because of higher resolution, with reduced dose exposure. The CBCT scan confirmed aerated middle ears, and there was a hypodense fissula ante fenestram, thick stapes, and thick footplate on both sides. The middle ear cavities were malformed with a narrow epitympanic recess (Fig. 1). MRI showed a contrastenhancing nodule in the right IAC at the location of Scarpa’s ganglion with a diameter of 1 mm (Fig. 2).
CASE PRESENTATION A 26-year-old man presented because he was unsatisfied with the hearing aid prescribed a year earlier at another institution. The clinical genetic diagnosis of Myhre syndrome was made at the age of 24 based on facial dysmorphism, thick skin, muscular hypertrophy, mental retardation, and limited joint mobility. Molecular genetic testing showed a de novo heterozygous p.Arg496Cys mutation in the SMAD4 gene, consistent with the clinical diagnosis as previously published by Le Goff et al. (2). There was hearing loss since childhood, and a hearing aid was used since the age of 8, which became inadequate because of progressive hearing loss. The parents had normal hearing, but his sister had surgery for otosclerosis at the age of 36. Micro-otoscopy showed an intact tympanic
DISCUSSION We report a case of Myhre syndrome with bilateral otospongiosis and a right sided tumor in the IAC compatible with a VS. Hearing loss is reported in 12 of 14 male patients and in 7 of 8 female Myhre syndrome patients. The type of hearing loss is not always clearly defined in these case reports, but most of them seem to be conductive or mixed. One report comments on the temporal bone findings in a patient on CT (3). The authors report a bilateral thick stapedial footplate fused with the oval window on the right side, and they concluded to primary stapedial dysplasia or otosclerosis. The dysplasia hypothesis was supported by the absent progression of the hearing loss. Another report concluded that because of the absent improved hearing after grommet insertion, the deafness had to be due to ossicular fixation. These reports are consistent with our findings of otospongiosis. We do
Address correspondence and reprint requests to Christoph Kenis, M.D., Department of Radiology, Sint-Jan Hospital, Bruges, Belgium, Bruges, Belgium; E-mail: [email protected] The authors disclose no conflicts of interest.
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Copyright © 2014 Otology & Neurotology, Inc. Unauthorized reproduction of this article is prohibited.
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C. KENIS ET AL.
FIG. 1. A, Double-oblique reformatted cone-beam CT image of the right ear at the level of the oval window shows a hypodense fissula ante fenestram (arrow), a thickened stapes footplate (arrowhead ), and a thickened stapes (large arrow). B, Coronal cone-beam CT image shows a narrow epitympanic recess with close contact of the incus body with the lateral epitympanic wall (arrow). These findings were present bilaterally. EAC indicates external auditory canal; IAC, internal auditory canal.
not have arguments for stapedial dysplasia, but both stapes were uniformly thick. This is most likely the result of a congenital malformation taking into account that there also was a malformed middle ear cavity. There was also a dysplastic lateral semicircular canal in our patient, which is a relatively common congenital malformation. The thickened footplate is most likely due to otospongiosis, but it can also be the result of a congenital malformation or inflammation. As otosclerosis is present in his sister, it is not possible to make definite conclusions about the cause of otospongiosis in our patient. Otosclerosis is a genetic disorder with dominant or complex inheritance. In dominant forms, penetrance is variable and even if the parents are healthy, this type of otosclerosis cannot be excluded in our patient and his sister. We do report the first MRI
finding of a nodule in the IAC consistent with a VS in a patient with Myhre syndrome. The VS could have had an effect on the perceptive component of the hearing loss, but because these components were symmetric, the VS may just be an incidental finding. This case, however, raises the discussion on the role of transforming growth factor-A1 (TGFA1) in the pathogenesis of both otospongiosis and VS. The SMAD4 gene encodes for a protein that has a role in signal transduction of TGFA1 (2). Interestingly, a coding variant in TGFA1 has been associated with otosclerosis (4). The role of TGFA1 in the growth of VS has been the topic of investigation and is still not fully understood (5). Although the otospongiosis in our case may be attributable to dominant inheritance, CT is useful for excluding otospongiosis in Myhre syndrome patients presenting
FIG. 2. A and B, Axial (A) and coronal (B) gadolinium-enhanced T1-weighted magnetic resonance (MR) image of the right ear at the level of the internal auditory canal shows an enhancing nodule on Scarpa’s ganglion (arrow) consistent with a small vestibular schwannoma. C, Axial 3D-TSE T2-weighted MR image shows replacement of the normal IAC fluid signal by the nodule on Scarpa’s ganglion (arrow). IAC indicates internal auditory canal; VCN, vestibulocochlear nerve. Otology & Neurotology, Vol. 35, No. 9, 2014
Copyright © 2014 Otology & Neurotology, Inc. Unauthorized reproduction of this article is prohibited.
MYHRE SYNDROME with hearing loss. MRI can exclude a VS and inner ear malformations. REFERENCES 1. Myhre SA, Ruvacalba HA, Graham CB. A new growth deficiency syndrome. Clin Genet 1981;20:1Y5. 2. Le Goff C, Mahaut C, Abhyankar A, et al. Mutations at a single codon in Mad homology 2 domain of SMAD4 cause Myhre syndrome. Nat Genet 2011;44:85Y8.
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3. Burglen L, He´ron D, Moerman A, et al. Myhre syndrome: new reports, review, and differential diagnosis. J Med Genet 2003;40: 546Y51. 4. Thys M, Schrauwen I, Vanderstraeten K, et al. The coding polymorphism T263I in TGF-beta1 is associated with otosclerosis in two independent populations. Hum Mol Genet 2007;16: 2021Y30. 5. Lo¨ttrich M, Mawrin C, Chamaon K, et al. Expression of transforming growth factor-A receptor type 1 and 2 in human sporadic vestibular schwannoma. Pathol Res Pract 2007;203:245Y9.
Otology & Neurotology, Vol. 35, No. 9, 2014
Copyright © 2014 Otology & Neurotology, Inc. Unauthorized reproduction of this article is prohibited.
Imaging Case of the Month
Bilateral Otospongiosis and a Unilateral Vestibular Schwannoma in a Patient With Myhre Syndrome *Christoph Kenis, †Margriet Verstreken, *Katrien Gieraerts, ‡Bert De Foer, §Nathalie Van der Aa, †Erwin F. Offeciers, and *‡Jan W. Casselman *Department of Radiology, Sint-Jan Hospital, Bruges; ÞEuropean Institute for ORL, and þDepartment of Radiology, Sint-Augustinus Hospital, Wilrijk; and §Department of Medical Genetics, University and University Hospital Antwerp, Edegem, Belgium
Myhre syndrome is a rare disorder characterized by facial dysmorphism, short stature, generalized muscle hypertrophy, skeletal anomalies, and limited joint mobility (1). Hearing loss is frequently reported. The clinical findings have been described in 22 cases till date, and recently, a de novo dominant mutation in the SMAD4 gene was discovered in 19 patients (2). We report a case of Myhre syndrome with bilateral mixed hearing loss and bilateral fenestral otospongiosis on cone-beam computed tomography (CBCT). Magnetic resonance imaging (MRI) also revealed a nodule in the right internal auditory canal (IAC) compatible with a vestibular schwannoma (VS). No high resolution images of the temporal bone in patients with Myhre syndrome have been published, to the best of our knowledge.
membrane (TM) and normally aerated middle ear on the left side. The right TM was sclerotic with normal middle ear aeration assumed. Audiometry showed bilateral severe mixed hearing loss (air conduction: pure tone average (PTA) (0.5-1-2 kHz) = 105 dBHL right ear, 107 dBHL left ear; bone conduction: PTA (0.5-1-2kHz) = 67 dBHL right ear, 70 dBHL left ear). There were absent stapedius muscle reflexes on tympanometry, and the tympanogram showed a flat curve (type B) bilaterally. CBCT allows a better definition of small structures compared with conventional multislice CT scanners because of higher resolution, with reduced dose exposure. The CBCT scan confirmed aerated middle ears, and there was a hypodense fissula ante fenestram, thick stapes, and thick footplate on both sides. The middle ear cavities were malformed with a narrow epitympanic recess (Fig. 1). MRI showed a contrastenhancing nodule in the right IAC at the location of Scarpa’s ganglion with a diameter of 1 mm (Fig. 2).
CASE PRESENTATION A 26-year-old man presented because he was unsatisfied with the hearing aid prescribed a year earlier at another institution. The clinical genetic diagnosis of Myhre syndrome was made at the age of 24 based on facial dysmorphism, thick skin, muscular hypertrophy, mental retardation, and limited joint mobility. Molecular genetic testing showed a de novo heterozygous p.Arg496Cys mutation in the SMAD4 gene, consistent with the clinical diagnosis as previously published by Le Goff et al. (2). There was hearing loss since childhood, and a hearing aid was used since the age of 8, which became inadequate because of progressive hearing loss. The parents had normal hearing, but his sister had surgery for otosclerosis at the age of 36. Micro-otoscopy showed an intact tympanic
DISCUSSION We report a case of Myhre syndrome with bilateral otospongiosis and a right sided tumor in the IAC compatible with a VS. Hearing loss is reported in 12 of 14 male patients and in 7 of 8 female Myhre syndrome patients. The type of hearing loss is not always clearly defined in these case reports, but most of them seem to be conductive or mixed. One report comments on the temporal bone findings in a patient on CT (3). The authors report a bilateral thick stapedial footplate fused with the oval window on the right side, and they concluded to primary stapedial dysplasia or otosclerosis. The dysplasia hypothesis was supported by the absent progression of the hearing loss. Another report concluded that because of the absent improved hearing after grommet insertion, the deafness had to be due to ossicular fixation. These reports are consistent with our findings of otospongiosis. We do
Address correspondence and reprint requests to Christoph Kenis, M.D., Department of Radiology, Sint-Jan Hospital, Bruges, Belgium, Bruges, Belgium; E-mail: [email protected] The authors disclose no conflicts of interest.
e253
Copyright © 2014 Otology & Neurotology, Inc. Unauthorized reproduction of this article is prohibited.
e254
C. KENIS ET AL.
FIG. 1. A, Double-oblique reformatted cone-beam CT image of the right ear at the level of the oval window shows a hypodense fissula ante fenestram (arrow), a thickened stapes footplate (arrowhead ), and a thickened stapes (large arrow). B, Coronal cone-beam CT image shows a narrow epitympanic recess with close contact of the incus body with the lateral epitympanic wall (arrow). These findings were present bilaterally. EAC indicates external auditory canal; IAC, internal auditory canal.
not have arguments for stapedial dysplasia, but both stapes were uniformly thick. This is most likely the result of a congenital malformation taking into account that there also was a malformed middle ear cavity. There was also a dysplastic lateral semicircular canal in our patient, which is a relatively common congenital malformation. The thickened footplate is most likely due to otospongiosis, but it can also be the result of a congenital malformation or inflammation. As otosclerosis is present in his sister, it is not possible to make definite conclusions about the cause of otospongiosis in our patient. Otosclerosis is a genetic disorder with dominant or complex inheritance. In dominant forms, penetrance is variable and even if the parents are healthy, this type of otosclerosis cannot be excluded in our patient and his sister. We do report the first MRI
finding of a nodule in the IAC consistent with a VS in a patient with Myhre syndrome. The VS could have had an effect on the perceptive component of the hearing loss, but because these components were symmetric, the VS may just be an incidental finding. This case, however, raises the discussion on the role of transforming growth factor-A1 (TGFA1) in the pathogenesis of both otospongiosis and VS. The SMAD4 gene encodes for a protein that has a role in signal transduction of TGFA1 (2). Interestingly, a coding variant in TGFA1 has been associated with otosclerosis (4). The role of TGFA1 in the growth of VS has been the topic of investigation and is still not fully understood (5). Although the otospongiosis in our case may be attributable to dominant inheritance, CT is useful for excluding otospongiosis in Myhre syndrome patients presenting
FIG. 2. A and B, Axial (A) and coronal (B) gadolinium-enhanced T1-weighted magnetic resonance (MR) image of the right ear at the level of the internal auditory canal shows an enhancing nodule on Scarpa’s ganglion (arrow) consistent with a small vestibular schwannoma. C, Axial 3D-TSE T2-weighted MR image shows replacement of the normal IAC fluid signal by the nodule on Scarpa’s ganglion (arrow). IAC indicates internal auditory canal; VCN, vestibulocochlear nerve. Otology & Neurotology, Vol. 35, No. 9, 2014
Copyright © 2014 Otology & Neurotology, Inc. Unauthorized reproduction of this article is prohibited.
MYHRE SYNDROME with hearing loss. MRI can exclude a VS and inner ear malformations. REFERENCES 1. Myhre SA, Ruvacalba HA, Graham CB. A new growth deficiency syndrome. Clin Genet 1981;20:1Y5. 2. Le Goff C, Mahaut C, Abhyankar A, et al. Mutations at a single codon in Mad homology 2 domain of SMAD4 cause Myhre syndrome. Nat Genet 2011;44:85Y8.
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3. Burglen L, He´ron D, Moerman A, et al. Myhre syndrome: new reports, review, and differential diagnosis. J Med Genet 2003;40: 546Y51. 4. Thys M, Schrauwen I, Vanderstraeten K, et al. The coding polymorphism T263I in TGF-beta1 is associated with otosclerosis in two independent populations. Hum Mol Genet 2007;16: 2021Y30. 5. Lo¨ttrich M, Mawrin C, Chamaon K, et al. Expression of transforming growth factor-A receptor type 1 and 2 in human sporadic vestibular schwannoma. Pathol Res Pract 2007;203:245Y9.
Otology & Neurotology, Vol. 35, No. 9, 2014
Copyright © 2014 Otology & Neurotology, Inc. Unauthorized reproduction of this article is prohibited.
