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Abstract
We report a child, diagnosed with Coffin-Siris syndrome (CSS), with chronic right otorrhoea. CT and DR-MRI were performed to further investigate, diagnose and determine relevant surgical anatomy. CT temporal bones assessment was performed, and the measurements compared with previously published data for normal temporal bone anatomy. These comparisons highlighted various differences which were not initially expected; it showed that there were multiple inner ear abnormalities in addition to middle ear disease. This case highlights the importance of considering temporal bone abnormalities in all children with CSS or any dysmorphia, when they may require mastoid procedures. Reviewing the management of this case provides relevant learning opportunities for both primary, secondary and tertiary care institutions.
- ear
- nose and throat/otolaryngology
- genetics
- radiology
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Background
Multiple healthcare professionals can illicit learning opportunities from this case. Ear infections are one of the most common childhood conditions presenting to primary care. Prompt management is vital to reduce permanent hearing damage and speech and language delay, this is even more vital when considering children with other medical conditions or developmental delay. Non-resolving cases in children with dysmorphia should be promptly referred to tertiary units for further investigation and management as treatment may require more expertise. Although Coffin-Siris syndrome (CSS) is rare, it highlights the more global message that children with dysmorphia may have altered anatomy which may not have been previously reported. This is imperative for surgeons to remember when considering to operate.
Case presentation
A 7-year-old child, with global developmental delay and awaiting genetic diagnosis for an unknown dysmorphic syndrome, attended his local Ear, Nose and Throat (ENT) department suffering from bilateral otalgia and otorrhoea. He was treated for otitis externa and occasional acute otitis media. Bilateral behind-the-ear hearing aids successfully managed his maximal conductive hearing loss. After several years, he began to suffer from unilateral right otorrhoea and was unable to tolerate his hearing aid. Due to his complicated medical history, referral was made to the regional paediatric ENT centre for management. The right ear demonstrated abnormal keratin migration, subtotal perforation of the tympanic membrane, squamous replacement of the handle of malleus and reactive middle ear mucosa. The left tympanic membrane was intact but was crossed by an abnormal band as seen in first branchial cleft anomaly.1 High-resolution CT and DR-MRI were performed to investigate for cholesteatoma and determine relevant surgical anatomy. During this investigative period, he was diagnosed with CSS with a mosaic mutation in the ARID1A gene, a recognised genetic anomaly.
Investigations and results
The CT imaging was performed on a GE OPTIMA 660 multislice scanner set at 120 kV, 140 mA and 0.5 s rotation. Slice thickness was 0.625 mm with 0.312 interval overlapping reconstructions at pitch 0.351:1. Scans were reconstructed on a high-resolution bone algorithm. The scans were analysed and measurements made on a SECTRA PACS workstation, from 0.6 mm contiguous slices parallel and perpendicular to the lateral semicircular canal and modified Poschl views.2 Window width/level was 4000/500. The bone/soft tissue interface identified visually by the authors at time of measurement.3 Turbo spin-echo axial diffusion-weighted imaging sequence MRI was performed on a Philips 1.5T Ingenia Scanner, slice thickness 3 mm, no gap, b=1000 m/s. The measurements were compared with previously published data for normal temporal bone anatomy.4 5 The z-score, a representative of the position of a value on a normal distribution, was calculated. A standard z-table or normal value table was used to calculate the p value, with significance being deemed as p0.95. The cochlea of the child with Coffin-Siris demonstrated normal size apical and basal turns in both anteroposterior (AP) and transverse dimensions. Despite this, the modiolus was large in AP but normal length transversely. The bony island of the lateral semicircular canal was small, and the vestibule narrow but again of normal length. The final abnormal finding was of a funnel-shaped internal acoustic canal (figures 1 and 2). The canal was normal in length, however was broad both at the porous acousticus and mid-distance point. Facial nerve architecture was normal on CT imaging, and its bony covering intact. MRI showed no other abnormalities. The p values for these findings are shown in table 1.
Coffin-Siris temporal bone measurements (mm), z-score and p-value (probability)
CT image demonstrating small bony islands in lateral semicircular canal and funnel-shaped internal acoustic canal.
CT image demonstrating narrow vestibule, but of normal length and elongated (within the anteroposterior dimension) modiolus.
Outcome and follow-up
The patient we report in this case is now an adolescent and over 8 years after initial presentation to ENT services. Cross-sectional imaging confirmed no presence of cholesteatoma. Due to his chronic suppurative otitis media, he received a right bone-anchored hearing aid several years ago which he manages very well, and this has made a great difference to his quality of life. After several years of regular ENT follow-up, we are pleased to report that his chronic suppurative otitis media has resolved. He continues to receive regular audiology follow-up regarding his hearing.
Discussion
A variety of congenital malformations of the ear and temporal bone have been described in the literature.6 Some of these abnormalities are part of well-described genetic syndromes, whereas others are sporadic.6 They may frequently cause conductive, sensorineural or mixed hearing loss. Enlargement of the vestibular aqueduct is the most common congenital malformations of the temporal bone. It may occur in isolation or with other abnormalities such as incomplete cochlear partition.6 Genetic disorders which involve these abnormalities include large vestibular aqueduct syndrome and Pendred syndrome. Other well-described syndromes with inner ear anomalies include CHARGE syndrome and branchio-oto-renal syndrome which can have a variety of abnormalities ranging from aplasia or hypoplasia of the semicircular canals, enlarged vestibular aqueducts, small internal acoustic canal or incomplete formation of the cochlea.6
CSS is a rare disorder with less than 200 reported cases in the literature.7 It is caused by mutations in genes-encoding components of the BRM-associated factor complex, also known as the mammalian SWItch/sucrose non-fermentable-like complex.8 While the mutations responsible for CSS appear to exhibit complete penetrance, the diagnosis was as recently as the past decade entirely clinical with genetics playing a supporting role. It is characterised by a number of clinical features including intellectual disability, growth deficiency, microcephaly, coarse facial features, and hypoplastic or absent fifth fingernails and/or toenails.9 These are more clearly defined due to the discovery of gene mutations linked with CSS.10 The most common of these gene mutations, ARID1B, has been identified in 37% of patients with CSS. While the ARID1A gene mutation, which was identified in this case, accounts for a much smaller number of around 5%.11 The variability in phenotype seems most marked in ARID1A and ARID1B patients compared with other mutations identified in CSS.11 ARID1A mutations are associated with the severest phenotypes.12 A previous study comparing 71 patients with CSS attempted to illicit characteristic clinical features specific to particular mutated genes for CSS, however, all that could be deduced was that patients with CSS with SMARCB1, SMARCA4, ARID1A or SMARCE1 mutations showed hypoplastic/absent fifth finger/toenails, but some patients with ARID1B mutations did not.9 The natural history of the condition sees frequent reports of hearing impairment with the ARID1B mutation being most strongly linked to hearing impairment.13 Despite these associations between CSS and hearing loss, there are no reports of temporal bone anomalies.
In this manuscript, we report a case of CSS with significant temporal bone abnormalities. The presence of small bony islands suggests abnormal fusion and ossification of the lateral semicircular canal. However, the significance of the long modiolus and funnel-shaped internal acoustic meatus is less clear. The latter having been reported as a normal variant.14 The presence of altered anatomy raises questions of the potential role of the genetic mutations being identified in CSS within temporal bone anatomy; however, clarification of this issue will require assessment of a greater number of cases of CSS.
This case highlights the importance of considering temporal bone abnormalities in all children with dysmorphia not just those with CSS. It is noteworthy that these children may have altered anatomy which has not previously been reported, which was the case with this patient. Paediatric patients with congenital hearing loss may require middle ear surgery or cochlear implantation depending on the cause. In these cases, cross-sectional imaging is vital as the risk of a loss of orientation and iatrogenic damage to structures of the temporal bone are increased due to their altered orientation.
Learning points
Early referral to tertiary centres should be considered with any child with dysmorphia.
Always consider the potential of unreported anatomical abnormalities in children with dysmorphia requiring surgical intervention.
Altered surgical approach may be necessary in children with dysmorphia.
Footnotes
Contributors JW—lead author. CL—coauthor and review of the manuscript. SM—complied radiology measurements used in the manuscript. KT—patient’s consultant and review of the manuscript.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent for publication Parental/guardian consent obtained.
Provenance and peer review Not commissioned; externally peer reviewed.