CT findings of the temporal bone in CHARGE syndrome: aspects of importance in cochlear implant surgery

The criteria for the clinical diagnosis of CHARGE syndrome (MIM, Mendelian Inheritance in Man, 214800), have been defined by Blake et al. and Verloes [1, 2]. CHARGE syndrome is an acronym of Coloboma, Heart disease, choanal Atresia, Retardation, Genital hypoplasia, and Ear anomalies. Organ involvement and severity is highly variable amongst affected patients. A major criterion includes the condition of the temporal bone, which may be hypoplastic or show an absence of the semicircular canals, according to Verloes. Anomalies are seen in the external, middle and inner ear, such as the typically low-set, cup-shaped ears, ossicular malformations, an aberrant course of the facial nerve, hypoplastic internal auditory canal, and an abnormally developed cochlea. Some of these malformations can cause hearing loss: 60–90 % of patients with CHARGE syndrome have moderate to severe hearing loss due to conductive, sensorineural or mixed defects. In most patients, hearing loss can be partially compensated with hearing aids. When hearing aids do not have the desired outcome due to the presence of profound to severe hearing loss, cochlear implantation may be considered. If cognitive disabilities, developmental and behavioural problems do not preclude cochlear implantation, a thorough assessment of the temporal bone anatomy is necessary. Anatomical alterations pose additional surgical risks during the implantation, by hampering the surgical approach to the cochlea or the insertion of the electrode array into the cochlea, and they may influence the surgical results in terms of speech perception.

In 2004, the causative gene for CHARGE syndrome was identified as CHD7 on chromosome 8q12.1 [3]. Since then, 528 different mutations of the gene have been described, but no clear genotype-phenotype correlation could be recognized (www.​CHD7.​org) [4]. In the CHD7 mutation positive patients, the most common clinical findings were temporal bone anomalies (98 %), external ear malformations (91 %), and hearing loss (89 %) [5].

The main goal of this retrospective study was to analyse the presence of the anomalies of the temporal bone and the cochlear nerve in patients with CHARGE syndrome and their potential impact on cochlear implant surgery planning. The secondary goal was to study possible genotype-phenotype correlations.

We collected analogue and digital CT studies of the temporal bone of patients attending the Dutch CHARGE center of expertise (University Medical Center Groningen, the Netherlands), after obtaining written informed consent from all patients or their legal representatives.

All patients had molecularly confirmed CHARGE syndrome, or clinically typical CHARGE syndrome according to the Blake or Verloes criteria (Tables 1, 4) except for one patient with atypical CHARGE syndrome (patient 12), because the parents did not wish further investigation [1, 2].

The patients were investigated in different time periods and in different Dutch hospitals, so the scans were made with different scanner types and variable scan parameters.

We evaluated CTs of 84 ears of 42 patients (22 male, 20 female) with CHARGE syndrome (29 digital and 13 analogue scans). The scans were performed between 1996– 2010. The mean age of the patients at the time of scanning was 6.4 years, median 2.5 years (SD 9.8; min 0, max 47 years).

Temporal bone anomalies detected by CT are important when planning an operation. Vascular variations, missing anatomical landmarks such as the lateral semicircular canal or the vestibular system, an aberrant course of the facial nerve, or stenosis of the round window may hamper safe surgical access to the round window. Given our findings, when planning CI or ear surgery, care must be taken with regard to the reduced development of the mastoid, leading to a smaller access to the middle ear, especially in young children. In these cases, an endaural approach instead of a mastoidectomy [7], or a temporary intra-operative removal or anterior displacement of the posterior wall of the outer ear canal could be considered. Vascular anomalies could also complicate a mastoidectomy, since these may cause uncontrollable bleeding during surgery or postoperative thrombosis of the sigmoid sinus [8‐10]. In our group of CHARGE patients, large emissary veins and a persistent petrosquamosal sinus were often present. Whereas emissary veins through the temporal squama are a common anatomical variant [11, 12] and easily dealt with during surgery, a persistent petrosquamosal sinus is rare in the general population (Koesling et al. [11] estimated this at 1 %). However, several authors have reported it to be present in 11–89 % of CHARGE patients [9, 13‐15]. The highest incidence was described by Giesemann et al. [14], in patients who all had aplasia of the SCCs. In our patient population, which included patients with partially and fully developed vestibular systems, a persistent petrosquamosal sinus was seen in 13 %. The persistent petrosquamosal sinus can impede the surgical approach, this can be a reason to choose the contra lateral ear for CI.

SCC aplasia is a hallmark of CHARGE syndrome. CHD7 is highly expressed in the developing ear and is required for development of the SCCs. Delayed fusion and altered gene expression contribute to SCC defects in CHD7-deficient mice [16]. Currently, the presence of SCC abnormalities is considered an important indication for performing sequencing of the CHD7 gene and diagnosis [17]. In our study, we found that normal SCC were present in only one patient. However, during mastoidectomy, the lateral SCC serves as an important anatomical landmark, so the appearance of the SCCs, ranging from complete absence of all canals to normal development, should be meticulously described [7, 13]. In case of a lateral SCC aplasia, the tegmen serves as a paramount marker to direct the surgeon towards the antrum. Anomalies of the SCCs were associated with hypoplasia of the vestibule and a shortened vestibular aqueduct coursing straight to the posterior fossa. This confirms what was reported by Morimoto et al.: ‘An aberrant course of the vestibular aqueduct is hypothesized to be the result of semicircular aplasia and the associated displacement of normal surrounding structures’ [9].

The facial nerve is another structure at risk during cochlear implantation. As described in the literature, the facial nerve often showed an aberrant course in its tympanic or mastoidal portion [9, 13, 18]. The more medial course of the mastoidal portion of the facial nerve allows a surgeon to create a wider entrance to the middle ear (through a posterior tympanotomy). However, the aberrant course of the tympanic segment of the facial nerve, in particular when it covers the round window, may complicate creating the cochleostomy for intracochlear insertion of the cochlear implant. The aberrant facial nerve may be at risk of injury during cochleostomy [19] or may even be a reason to abort the implantation [20]. The association we observed of an aberrant course of the facial nerve with dysplastic stapes and absence of the oval window was described by Zeifer et al. in different aetiologies without CHARGE syndrome [21].

Absence or stenosis of the oval window was present in more than two-thirds of our patients and is a well-known feature in CHARGE syndrome [9, 13, 22, 23]. Stenosis or absence of the round window was seen less often (as confirmed in the literature). Yet this poses an additional challenge for the surgeon in choosing the optimal site for a cochleostomy.

The size and shape of the cochlea will influence the choice of CI-type. According to the literature, the cochlea is dysplastic in between 20 and 100 % of the ears described in patients with CHARGE syndrome [9, 18, 24, 25]. The anomalies vary from a fused second and apical turn to a cochlea with 1.5 turns [26‐28]. We describe several cases with a shortened cochlea despite the presence of a basal, second and apical turn (referred to as hypoplasia type IV). To the best of our knowledge, this cochlear appearance has not been described in CHARGE syndrome before, but it appears to be consistent with the description of cochlear hypoplasia type IV in a recently published study by Sennaroglu [29] or may be comparable with the flattened cochlea observed by Elmaleh et al. [30] in patients with Waardenburg syndrome. However, the other temporal bone anomalies described in Waardenburg syndrome, besides SCC aplasia and the flattened cochlea, differ from our findings.

Both this cochlear anomaly, as well as the IPII and hypoplasia type III found in this study, should not cause any problems for the insertion of an electrode array as opposed to more severe malformations [31, 32]. The successful outcome of a cochlear implantation also depends on the presence of the cochleo-vestibular nerve.

In our phenotype-genotype analysis we showed that total aplasia of the SCC and oval window aplasia is more common in patients with truncating mutations than in those with non-truncating mutations—in agreement with the results of Corsten-Janssen et al. showing more anomalies in patients with truncating mutations [33]. Remarkably, the distribution of mutations present in our cohort differs from that reported for large cohorts in the literature. Our percentage of patients with non-truncating mutations (splice-site and missense) was relatively high with 35.7 % in comparison to Zentner et al. [5] and to Janssen et al. [4] who reported 23 and 20 % of patients with non-truncating mutations, respectively. This discrepancy might be because a CT is often used in mildly affected patients to check the semicircular canals and to provide further proof for the clinical diagnosis. Our cohort might be enriched with more mildly affected patients (12/42), and thus of missense mutations.

In general, we conclude that temporal bone findings in patients with CHARGE syndrome vary widely and should therefore be studied meticulously before performing any surgery. Imaging may exclude patients from cochlear implantation or reveal an aberrant course of the facial nerve, vascular and middle ear abnormalities that could complicate CI surgery. Such information is valuable and should be combined with records on the developmental and behavioural problems that are also common in CHARGE syndrome. Moreover, patients with CHARGE syndrome often have post-surgical complications due to their neurological and anatomical abnormalities [34]. A balance between the benefit of CI, the surgical procedure’s chance of success, and the anaesthetic risks should be sought by a multi-disciplinary team working with the patient and his/her family.