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Torticollis in children with enlarged vestibular aqueducts
International Journal of Pediatric Otorhinolaryngology 131 (2020) 109862
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Torticollis in children with enlarged vestibular aqueducts a,b,∗
a,1
a,2
T a
Jacob R. Brodsky , Karampreet Kaur , Talia Shoshany , Juliana Manganella , Devon Barretta, Kosuke Kawaia,b, Makenzie Murrayc, Greg Licamelia,b, Victoria Albanoa, Amanda Stolzera, Margaret Kennaa,b a
Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA Harvard Medical School, 243 Charles Street, Boston, MA, 02114, USA c Northeastern University, 360 Huntington Ave, Boston, MA, 02115, USA b
A R T I C LE I N FO
A B S T R A C T
Keywords: Torticollis Paroxysmal EVA Enlarged vestibular aqueduct Pendred
Objectives: To evaluate the association between torticollis and enlarged vestibular aqueduct (EVA). Methods: An online/phone survey was administered to parents of 133 children diagnosed with the following disorders: EVA, GJB2 (Connexin 26) mutations associated congenital hearing loss and epistaxis (control). The survey included questions regarding symptoms of torticollis, vertigo, and hearing loss. Results: Patients with EVA had a 10-fold greater odds of having torticollis than controls (31% vs. 4%; OR = 10.6; 95% CI: 2.9, 39.2). No patients with GJB2 had a reported history of torticollis. Torticollis preceded the diagnosis of hearing loss in most (87%) patients with EVA who had a reported history of torticollis. EVA patients were more likely to have reported motor delay than controls (40% vs. 15%; p = 0.002). EVA patients with prior torticollis (80%; 12/15) were more likely to have balance impairment than EVA patients without prior torticollis (12%; 4/33; p < 0.001). Twelve patients had a reported history of paroxysmal torticollis, all of whom had EVA. Conclusion: Torticollis in infants may be a marker of EVA. Infants with torticollis should be monitored closely for hearing loss and motor delay, especially when the torticollis is paroxysmal.
1. Introduction Approximately 5 out of every 1000 children in the United States have a unilateral or bilateral moderate to profound hearing loss [1], but less than half are detected or present at the time of newborn hearing screening [2]. Up to 16% of cases of sensorineural or mixed hearing loss in children are associated with enlarged vestibular aqueducts (EVA) [3]. EVA is the most common structural temporal bone anomaly associated with congenital hearing loss [4]. Up to half of patients with EVA have either one or two mutant alleles of the SLC26A4 gene, which causes both Pendred syndrome and non-syndromic recessive hearing loss (DFNB4) [5]. The reported incidence of vestibular dysfunction in patients with EVA varies widely in the medical literature, with some of the larger published series reporting rates of vestibular symptoms between 4 and 47% [4,6,7]. The hearing loss in EVA varies in its clinical presentation, with some cases being stable over time, while others are fluctuating and/or progressive [4]. Therefore, hearing loss may not be
detected on newborn hearing screens or may not be present at birth in 30–60% of patients with EVA. Early identification and close audiologic monitoring is particularly important in patients with EVA, due to the high incidence of sudden and/or progressive hearing loss in many affected children. Torticollis is a persistent tilting of the head with rotation of the chin toward the contralateral shoulder, which results from contraction of the ipsilateral sternocleidomastoid muscle. Torticollis most commonly presents in infancy and can be either chronic or paroxysmal (intermittent). Chronic torticollis most commonly presents at birth (congenital torticollis) with an estimated prevalence between 0.3 and 2% [8]. It may present with a palpable mass in the sternocleidomastoid muscle that can be seen on imaging studies, which is known as fibromatosis colli. Most cases of congenital torticollis will resolve spontaneously or following a course of physical therapy. Other common causes of chronic torticollis in infants and young children include oculomotor disorders (e.g. strabismus, congenital nystagmus) and
∗ Corresponding author. Department of Otolaryngology and Communication Enhancement, Boston Children's Hospital, 300 Longwood Ave, Boston, MA, 02155, USA. E-mail address: [email protected] (J.R. Brodsky). 1 Present address: Vanderbilt University School of Medicine, 1161 21st Ave S, Nashville, Tennessee 37232, U.S.A. 2 Present address: Harvard Medical School, 243 Charles Street, Boston, MA 02114, U.S.A.
https://doi.org/10.1016/j.ijporl.2020.109862 Received 10 September 2019; Received in revised form 7 December 2019; Accepted 5 January 2020 Available online 07 January 2020 0165-5876/ © 2020 Published by Elsevier B.V.
International Journal of Pediatric Otorhinolaryngology 131 (2020) 109862
J.R. Brodsky, et al.
since birth). Subjects were categorized as experiencing “other” torticollis if torticollis symptoms did not meet these criteria, or if data on age of onset or frequency of episodes was incomplete. Patients with a reported history of nystagmus, strabismus, and/or eye surgery were excluded from the analysis to avoid inclusion of patients with torticollis of ophthalmologic origin. We performed an initial power analysis to determine needed sample sizes to achieve 80% power to detect a difference in the prevalence of prior history of torticollis by at least 20% between two groups, assuming a two-sided significance level of α = 0.05. This analysis yielded ideal sample sizes of 49 patients with EVA and 70 patients with epistaxis. We compared the prior history of torticollis between EVA patients and healthy controls using Fisher's exact or Chi-square test. Odds Ratio (OR) and 95% confidence interval (CI) were computed for the association between torticollis and EVA. Similarly, we compared motor delay, vertigo, and balance impairment between EVA patients and healthy controls. All statistical analyses were performed by a statistician using Statistical Analysis Software (SAS, Cary, NC).
plagiocephaly. Paroxysmal torticollis is typically attributed to vestibular dysfunction in young children, and has primarily been described in the setting of benign paroxysmal torticollis of infancy (BPTI), which is a condition primarily affecting infants and young children characterized by recurrent episodes of torticollis lasting for hours to days [9–12]. These episodes recur at a variable frequency, ranging from weeks to months between episodes. Several studies have found a link between BPTI and migraine, with 43–80% of BPTI patients having a family history of migraine [11,13–15]. We have observed a particularly high incidence of both chronic and paroxysmal torticollis in children with hearing loss associated with EVA. Our aim in this study was to determine if torticollis occurs at a higher rate in infants with hearing loss and EVA compared to children with hearing loss unrelated to EVA and to normal hearing controls. 2. Materials and methods 2.1. Participants
3. Results
We reviewed our internal databases of patients seen in the Balance and Vestibular Program and in the Hearing Loss Clinic at Boston Children's Hospital to identify patients seen by the junior (JB) or senior (MK) authors from January 2011–March 2017 that were given a diagnosis of EVA or hearing loss associated with biallelic GJB2 mutations. The GJB2 group served as a hearing loss control group, to help in differentiating whether torticollis is specifically associated with EVA or more generally with congenital hearing loss. Diagnosis of EVA was determined by radiologic criteria [16]. We also used outpatient billing records to identify patients seen over the same time period for evaluation of epistaxis, which were included as a control group. The absence of a recorded history of hearing loss in the control group patients was confirmed by medical record review, and all patients included in the study had undergone newborn hearing screening. Only patients who were ≤18 years of age at the time of diagnosis of torticollis, hearing loss, or epistaxis were included in the study.
3.1. Patient characteristics The study included forty-eight patients with EVA, 12 patients with biallelic GJB2 mutations, and 73 patients with epistaxis (healthy control group). An additional fourteen patients were excluded from the analysis due to a reported history of nystagmus, strabismus, and/or eye surgery. Mean age at the time of the survey was 9.3 (SD 4.6) years among patients with EVA, 11.1 (SD 4.6) years among healthy controls, and 6.7 (SD 4.1) years among patients with GJB2 mutations. Females made up 62% of the EVA group, 33% of the GJB2 mutation group, and 31% of the healthy control group, respectively. Among 48 patients with EVA, 23 patients had bilateral EVA and 25 patients had unilateral EVA. Mean age at initial hearing loss diagnosis was 3.0 (SD 2.6) years (range: 0–8 years). Seven patients in the EVA group reported a history of an abnormality in the SLC26A4 gene, though further details on these mutations were not available for analysis, as they were self-reported by the families completing the survey.
2.2. Data collection We generated an online survey using REDCap (Research Electronic Data Capture) software [17], which included questions about any history of episodes of head tilting or vertigo along with the temporal features of these symptoms. The survey also included questions about general patient demographics, hearing loss, and whether patients had a history of balance impairment, motor delay, and/or eye/vision problems. The same questionnaire was used for all subjects, but the REDCap survey included branching logic to facilitate efficiency of completion. For example, questions about further details of head tilting episodes were excluded if a respondent denied a history of tilting episodes, altogether. Families of included patients were sent letters by mail describing the study and were given the opportunity to opt out via prestamped postcards. Those who did not opt out after a two week period were contacted by phone and verbally consented to participate in the survey with a research assistant, or completed the survey over a secure email link sent directly from REDCap. Patients who met inclusion criteria were also recruited in person when seen for a clinic visit with one of the participating study providers. These patients completed the survey in person with a research assistant after providing verbal consent to participate. Each participant's survey responses were linked only to their diagnosis group and not to their name or any other specific patient identifiers in order to maintain anonymity. This study was approved by the Institutional Review Board at Boston Children's Hospital.
3.2. Torticollis Patients with EVA had a 10-fold greater odds of having torticollis than healthy controls (31% vs. 4%; OR = 10.6; 95% CI: 2.9, 39.2; p < 0.001; Table 1). Of the 12 patients with GJB2 mutations, none had a reported history of torticollis (31% in EVA vs. 0% in GJB2; p = 0.027; Table 2). Thirty-five percent (8/23) of patients with bilateral EVA had a reported history of torticollis, compared to 28% (7/25) of patients with unilateral EVA. Mean age of onset of torticollis among EVA patients was 2.4 (SD 3.3) months, and age of resolution was 18.6 ( ± 13.8) months. Thirteen (87%) of the 15 EVA patients with a history of torticollis had a reported onset of torticollis prior to the diagnosis of hearing loss, with a mean age of torticollis onset of 2.3 months and a mean age of hearing loss diagnosis of 39.7 months (Fig. 1). The onset of torticollis preceded the diagnosis of hearing loss in those thirteen patients by a mean of 43.4 months (more than 3.5 years). In the EVA group, hearing loss was reported to have been diagnosed at birth in ten patients without torticollis (20.8%) and in only two patients with torticollis (4.2%). Seven patients in the EVA group (14.6%) had a reported history of an abnormality in the SLC26A4 gene on genetic testing, only one of whom reported a history of torticollis (chronic). Among all 133 patients included in the analysis, twelve (9%) patients had a reported history of paroxysmal torticollis, all of whom had EVA. Out of all patients with EVA in the study, 25% had a reported history of paroxysmal torticollis. No patients with GJB2 or epistaxis (control) had a reported history of paroxysmal torticollis. All EVA patients with a reported history of paroxysmal torticollis also reported that the episodes had resolved prior to the time of
2.3. Statistical analysis Torticollis was categorized as paroxysmal (≥4 episodes of torticollis) or chronic (single episode of torticollis or continuous torticollis 2
International Journal of Pediatric Otorhinolaryngology 131 (2020) 109862
J.R. Brodsky, et al.
Table 1 Reported prior history of torticollis, vertigo, balance impairment, and gross motor delay in patients with enlarged vestibular aqueduct (EVA) compared to patients with epistaxis (control group).
Torticollis Paroxysmal torticollis Chronic torticollis Age of torticollis onset, months, mean (SD) Age of resolution, months, mean (SD) Vertigo Balance impairment Gross motor delay
EVA (n = 48)
Control (n = 73)
OR (95% CI)
p-value
15 (31%) 12 (25%) 3 (6%) 2.4 ( ± 3.3) 18.6 ( ± 13.8) 13 (27%) 16 (33%) 19 (40%)
3 (4%) 0 (0%) 1 (1%) 2.2 ( ± 3.8) 5.5 ( ± 3.5) 4 (5%) 6 (8%) 11 (15%)
10.6 (2.9, 39.2)
< 0.001
6.4 (1.9, 21.1) 5.6 (2.0, 15.6) 3.7 (1.6, 8.8)
0.002 < 0.001 0.003
EVA patients with torticollis (80%; 12/15) were more likely to have balance impairment than EVA patients without torticollis (12%; 4/33; p < 0.001). There was not a statistically significant difference in reported rates of gross motor delay, vertigo, or imbalance between the EVA and GJB2 groups (Table 2).
Table 2 Reported prior history of torticollis, vertigo, balance impairment, and gross motor delay in patients with enlarged vestibular aqueduct (EVA) compared to patients with GJB2-related hearing loss (“hearing loss control group”). EVA (n = 48)
GJB2 (n = 12)
OR (95% CI)
p-value
Torticollis Paroxysmal torticollis Chronic torticollis Vertigo Balance impairment
15 (31%) 9 (19%) 4 (8%) 13 (27%) 16 (33%)
0 0 0 2 2
–
0.027
Gross motor delay
19 (40%)
3 (25%)
(0%) (0%) (0%) (17%) (17%)
4. Discussion 2.5 (0.5, 12.8) 2.0 (0.5, 8.2)
0.71 0.32
Hearing loss has major implications for young children, but its identification may be delayed in children with a later onset hearing loss that was either absent at birth or was mild enough initially to be undetected on a newborn hearing screen, both of which are often the case with EVA. The observation in this study of a higher reported incidence of torticollis in babies with EVA may aid clinicians in the early detection of EVA-related hearing loss. Enlargement of the vestibular aqueducts was originally described by Mondini in 1791 in temporal bone specimens in conjunction with other anatomic anomalies of the cochlea that are seen in conjunction with EVA in some affected patients, including a cochlea with only 1.5 turns instead of the usual 2.5 turns as well absence of the interscalar septum between the middle and apical turns [4]. Recently, a new classification system for the radiologic patterns of inner ear malformations was defined by Sennaroglu and Saatci, which has become the standard approach for radiographically describing such anomalies [18]. Part of this classification includes two incomplete partition (IP) anomalies. Incomplete partition type II (IP-II) is the current terminology used to
0.51
survey completion. The mean reported age of paroxysmal torticollis resolution was 1.61 ( ± 1.34) months of age. 3.3. Motor delay, vertigo, and balance impairment Motor delay was reported in a significantly higher proportion of patients in the EVA group (40%) than in the control (epistaxis) group (15%; OR = 3.7; 95% CI: 1.6, 8.8; Table 1). Patients with EVA were more likely to experience vertigo (27%) or balance impairment (33%) than in the healthy control group (5% for vertigo and 8% for balance impairment). EVA patients who had a reported history of torticollis were more likely to also have reported motor delay (67%; 10/15) than EVA patients without torticollis (27%; 9/33; p = 0.01). Additionally,
Fig. 1. Age of onset of torticollis and hearing loss in fifteen children with enlarged vestibular aqueduct and associated hearing loss and torticollis. Torticollis onset preceded hearing loss onset in all but two patients. 3
International Journal of Pediatric Otorhinolaryngology 131 (2020) 109862
J.R. Brodsky, et al.
3.5–60 months) [11]. Many possible mechanisms have been proposed for the pathogenesis of BPTI, but none have been definitively established. The findings in our study suggest that many cases of paroxysmal torticollis in infants may be related to EVA instead of to BPTI. A quarter of EVA patients in our study group reported a history of paroxysmal torticollis, while none of the patients in the other groups had a reported history of paroxysmal torticollis. In 1969 Snyder and colleagues did propose that BPTI might be a form of labyrinthitis, due to the frequent association with other vestibular symptoms and the presence of three patients with hearing loss out of 12 patients with BPTI in their study [24]. One other study also recently described one patient with hearing loss of unknown etiology out of three patients with BPTI [10]. Not all patients in these studies had audiometry, and follow-up was also limited, so some cases of hearing loss may not have been identified. Only two EVA patients in our study with a reported history of torticollis (one paroxysmal and one chronic) had been diagnosed with hearing loss at birth, while none of the other ten EVA patients that were diagnosed with hearing loss at birth had reported torticollis. A theory that we propose for this phenomenon is that the torticollis episodes in infants with EVA may actually represent early signs of a progressively failing inner ear, while those with hearing loss at birth may not have torticollis episodes as the inner ear impairment has already stabilized. Another observation in support of this theory is that all seven patients with a reported history of abnormalities on SLC26A4 testing also had no history of paroxysmal torticollis symptoms. Some studies have found EVA patients with homozygous SLC26A4 gene mutations to have more severe hearing loss at an earlier average age, while EVA patients without SLC26A4 mutations are more likely to have more progressive and/or fluctuating hearing loss over time [5,25,26]. It is possible that a similar phenomenon may occur with the vestibular system of patients without SLC26A4 mutations, though further study with more objective determination of SLC26A4 mutation status in a larger number of patients would be needed to determine whether or not this is the case. The relationship between torticollis and vestibular dysfunction in EVA patients is further supported by the fact that no patients in the GJB2 group had reported torticollis, though it should be noted that there are reports of vestibular dysfunction in GJB2 patients, although at a much lower rate than with EVA [27]. We also found a significantly higher incidence of motor delay in the EVA group compared to the control group. Other studies have reported a high incidence of motor delay in children with EVA [6,7,28], which has been attributed to vestibular impairment [29–31]. We found a significantly higher rate of reported balance impairment in children in the EVA group who had a history of paroxysmal torticollis compared to those who did not. This supports a connection between paroxysmal torticollis in EVA patients and progressive vestibular loss. Based on this finding we recommend that infants with torticollis, especially those with paroxysmal torticollis, be screened early and monitored carefully for balance impairment and motor delay, so that physical therapy services can be initiated early enough to minimize delays when they begin to appear. A limitation of this study is the potential for recall bias due to the
describe what was previously referred to as the Mondini malformation. Valvasori and Clemens described the association between EVA and hearing loss in 1978 in 50 out of 3700 computerized tomography (CT) scans, which they used to establish the original radiologic criteria for the diagnosis of EVA [16]. Since that time a number of different radiologic measurements have been described for establishing the diagnosis of EVA, though currently the most commonly used criteria are those established in 2007 at Cincinnati Children's Hospital [19]. EVA can be either sporadic or can be associated with mutations in the SLC26A4 gene encoding the anion exchange protein pendrin, which can result in Pendred syndrome (EVA, hearing loss and thyroid dysfunction) or in nonsyndromic recessive deafness (hearing loss and EVA only; DFNB4) [5]. The mechanism behind the relationship between EVA and torticollis is not clear, though it is most likely related to dysfunction of the vestibular system. Torticollis is a common symptom of vestibular dysfunction in young children, which may be a response mediated by the vestibulo-colic reflex, which originates in the saccule organ of the vestibular labyrinth and affects the tone of the sternocleidomastoid muscle. This response is often abnormal in patients with EVA, resulting in abnormal cervical vestibular evoked myogenic potential testing, which may indicate dysfunction at the level of the saccule in these patients [20]. We have had the opportunity to observe a number of our own EVA patients during head tilting episodes, either in person or through parent-provided videos. We have found that they typically demonstrate a rotation of the chin to the opposite side of the head tilt consistent with contraction of the sternocleidomastoid muscle, as is seen in true torticollis. This is in contrast to a head tilt that would be seen from a skewed perception of the visual vertical. Many patients with EVA have vestibular symptoms and abnormalities on vestibular testing, though the incidence of vestibular dysfunction in EVA varies widely between studies [4,6,7]. In a 2015 prospective cohort study of 106 patients with EVA, Zalewski and colleagues reported that 44% of EVA patients had vestibular symptoms, and 45% had abnormalities on videonystagmography [6]. They also reported that 20% of EVA patients had reported a history of head tilting and vomiting at a prelingual age. This is the only prior report that we have been able to identify in the medical literature of an association between torticollis and EVA, though paroxysmal torticollis was not specifically described in that study and no specific details were provided on the head tilting beyond its reported incidence in the cohort. Additionally, Lu and colleagues did describe paroxysmal torticollis in a SLC26A4 knock-out mouse model [21]. Although chronic, congenital torticollis is quite common [22], the phenomenon of paroxysmal torticollis is more unusual and is of particular interest, since it occurred in 9% of patients in our study, all of whom had EVA. In the medical literature, paroxysmal torticollis has ubiquitously been attributed to BPTI, which is generally considered to be a migraine precursor disorder. The diagnostic criteria for this disorder are outlined in Fig. 2 [23]. Accompanying symptoms can include vomiting, irritability, ataxia, malaise and pallor, though often torticollis is the only evident symptom. A systematic review of 109 cases of BPTI from our program reported a mean age of onset of 5.9 months (range: 1 week–30 months) and a mean age of resolution of 31.4 months (range:
Fig. 2. Diagnostic Criteria for Benign Paroxysmal Torticollis of Infancy as outlined in the International Classification of Headache Disorders, 3rd edition. 4
International Journal of Pediatric Otorhinolaryngology 131 (2020) 109862
J.R. Brodsky, et al.
retrospective survey format. Mean ages in the EVA and control (epistaxis) groups were higher than in the GJB2 group at the time of the study, so parental recall of infantile symptoms may have been less accurate in the older groups. Also, there were more females in the EVA group than in the other groups, which could have impacted the relative incidences of torticollis in the groups. A prospective cohort study of torticollis in EVA patients and its relationship to motor development and vestibular function is warranted.
allele of SLC26A4, The Laryngoscope 127 (2017) E238–E243. [6] C.K. Zalewski, W.W. Chien, K.A. King, J.A. Muskett, R.E. Baron, J.A. Butman, et al., Vestibular dysfunction in patients with enlarged vestibular aqueduct, Otolaryngol. Head Neck Surg. 153 (2015) 257–262. [7] J.F. Grimmer, G. Hedlund, Vestibular symptoms in children with enlarged vestibular aqueduct anomaly, Int. J. Pediatr. Otorhinolaryngol. 71 (2007) 275–282. [8] K.K. Tomczak, N.P. Rosman, Torticollis, J. Child Neurol. 28 (2013) 365–378. [9] S.U. Cataltepe, T.F. Barron, Benign paroxysmal torticollis presenting as "seizures" in infancy, Clin. Pediatr. (Phila.) 32 (1993) 564–565. [10] A. Hadjipanayis, E. Efstathiou, D. Neubauer, Benign paroxysmal torticollis of infancy: an underdiagnosed condition, J. Paediatr. Child Health 51 (2015) 674–678. [11] N.P. Rosman, L.M. Douglass, U.M. Sharif, J. Paolini, The neurology of benign paroxysmal torticollis of infancy: report of 10 new cases and review of the literature, J. Child Neurol. 24 (2009) 155–160. [12] G. Sanner, B. Bergstrom, Benign paroxysmal torticollis in infancy, Acta Paediatr. Scand. 68 (1979) 219–223. [13] W.A. Al-Twaijri, M.I. Shevell, Pediatric migraine equivalents: occurrence and clinical features in practice, Pediatr. Neurol. 26 (2002) 365–368. [14] C. Bonnet, A. Roubertie, D. Doummar, N. Bahi-Buisson, V. Cochen de Cock, E. Roze, Developmental and benign movement disorders in childhood, Mov. Disord. 25 (2010) 1317–1334. [15] I.H. Pacheva, I.S. Ivanov, Migraine variants–occurrence in pediatric neurology practice, Clin. Neurol. Neurosurg. 115 (2013) 1775–1783. [16] G.E. Valvassori, J.D. Clemis, The large vestibular aqueduct syndrome, The Laryngoscope 88 (1978) 723–728. [17] P.A. Harris, R. Taylor, R. Thielke, J. Payne, N. Gonzalez, J.G. Conde, Research electronic data capture (REDCap)–a metadata-driven methodology and workflow process for providing translational research informatics support, J. Biomed. Inform. 42 (2009) 377–381. [18] L. Sennaroglu, I. Saatci, A new classification for cochleovestibular malformations, The Laryngoscope 112 (2002) 2230–2241. [19] M. Boston, M. Halsted, J. Meinzen-Derr, J. Bean, S. Vijayasekaran, E. Arjmand, et al., The large vestibular aqueduct: a new definition based on audiologic and computed tomography correlation, Otolaryngol. Head Neck Surg. 136 (2007) 972–977. [20] G. Zhou, Q. Gopen, Characteristics of vestibular evoked myogenic potentials in children with enlarged vestibular aqueduct, The Laryngoscope 121 (2011) 220–225. [21] Y.C. Lu, C.C. Wu, W.S. Shen, T.H. Yang, T.H. Yeh, P.J. Chen, et al., Establishment of a knock-in mouse model with the SLC26A4 c.919-2A > G mutation and characterization of its pathology, PLoS One 6 (2011) e22150. [22] M.C. Suhr, M. Oledzka, Considerations and intervention in congenital muscular torticollis, Curr. Opin. Pediatr. 27 (2015) 75–81. [23] The International Classification of Headache Disorders vol. 33, (2013) third ed., (Beta Version), Cephalalgia, 629-808. [24] C.H. Snyder, Paroxysmal torticollis in infancy. A possible form of labyrinthitis, Am. J. Dis. Child. 117 (1969) 458–460. [25] K.A. King, B.Y. Choi, C. Zalewski, A.C. Madeo, A. Manichaikul, S.P. Pryor, et al., SLC26A4 genotype, but not cochlear radiologic structure, is correlated with hearing loss in ears with an enlarged vestibular aqueduct, The Laryngoscope 120 (2010) 384–389. [26] C. Madden, M. Halsted, J. Meinzen-Derr, D. Bardo, M. Boston, E. Arjmand, et al., The influence of mutations in the SLC26A4 gene on the temporal bone in a population with enlarged vestibular aqueduct, Arch. Otolaryngol. Head Neck Surg. 133 (2007) 162–168. [27] K. Tsukada, H. Fukuoka, S. Usami, Vestibular functions of hereditary hearing loss patients with GJB2 mutations, Audiol. Neuro. Otol. 20 (2015) 147–152. [28] R.M. Rine, G. Cornwall, K. Gan, C. LoCascio, T. O'Hare, E. Robinson, et al., Evidence of progressive delay of motor development in children with sensorineural hearing loss and concurrent vestibular dysfunction, Percept. Mot. Skills 90 (2000) 1101–1112. [29] S.L. Cushing, B.C. Papsin, J.A. Rutka, A.L. James, K.A. Gordon, Evidence of vestibular and balance dysfunction in children with profound sensorineural hearing loss using cochlear implants, The Laryngoscope 118 (2008) 1814–1823. [30] S.L. Cushing, K.A. Gordon, J.A. Rutka, A.L. James, B.C. Papsin, Vestibular endorgan dysfunction in children with sensorineural hearing loss and cochlear implants: an expanded cohort and etiologic assessment, Otol. Neurotol. 34 (2013) 422–428. [31] A. De Kegel, L. Maes, H. Van Waelvelde, I. Dhooge, Examining the impact of cochlear implantation on the early gross motor development of children with a hearing loss, Ear Hear. 36 (2015) e113–121.
5. Conclusions The results from this study suggest that torticollis is more common in infants with EVA than in healthy controls or patients with non-EVA hearing loss, and may be an early marker of EVA, though further study of this relationship is warranted. Infants with paroxysmal torticollis or unexplained chronic torticollis may benefit from close audiological monitoring and motor screening. Pediatric providers may be able to use this approach to identify one of the most common causes of congenital hearing loss well before the hearing loss itself is evident, so that interventions for hearing loss and motor delay can be initiated as early as possible. Funding source All phases of this study were supported through internal funding provided by the Department of Otolaryngology and Communication Enhancement at Boston Children's Hospital. Meeting information The findings of this study were presented at the European Society of Pediatric Otolaryngology (ESPO) meeting in Stockholm, Sweden in June 2018. Declaration of competing interest None. Acknowledgement The authors would like to thank Alicia Wang, BS for her assistance in the preparation of this manuscript. References [1] C.A. Boyle, S. Boulet, L.A. Schieve, R.A. Cohen, S.J. Blumberg, M. Yeargin-Allsopp, et al., Trends in the prevalence of developmental disabilities in US children, 19972008, Pediatrics 127 (2011) 1034–1042. [2] A. Erenberg, J. Lemons, C. Sia, D. Trunkel, P. Ziring, Newborn and infant hearing loss: detection and intervention.American academy of pediatrics. Task force on newborn and infant hearing, 1998- 1999, Pediatrics 103 (1999) 527–530. [3] D.A. Preciado, L. Lawson, C. Madden, D. Myer, C. Ngo, J.K. Bradshaw, et al., Improved diagnostic effectiveness with a sequential diagnostic paradigm in idiopathic pediatric sensorineural hearing loss, Otol. Neurotol. 26 (2005) 610–615. [4] Q. Gopen, G. Zhou, K. Whittemore, M. Kenna, Enlarged vestibular aqueduct: review of controversial aspects, The Laryngoscope 121 (2011) 1971–1978. [5] J. Rose, J.A. Muskett, K.A. King, C.K. Zalewski, P. Chattaraj, J.A. Butman, et al., Hearing loss associated with enlarged vestibular aqueduct and zero or one mutant
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International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Torticollis in children with enlarged vestibular aqueducts a,b,∗
a,1
a,2
T a
Jacob R. Brodsky , Karampreet Kaur , Talia Shoshany , Juliana Manganella , Devon Barretta, Kosuke Kawaia,b, Makenzie Murrayc, Greg Licamelia,b, Victoria Albanoa, Amanda Stolzera, Margaret Kennaa,b a
Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA Harvard Medical School, 243 Charles Street, Boston, MA, 02114, USA c Northeastern University, 360 Huntington Ave, Boston, MA, 02115, USA b
A R T I C LE I N FO
A B S T R A C T
Keywords: Torticollis Paroxysmal EVA Enlarged vestibular aqueduct Pendred
Objectives: To evaluate the association between torticollis and enlarged vestibular aqueduct (EVA). Methods: An online/phone survey was administered to parents of 133 children diagnosed with the following disorders: EVA, GJB2 (Connexin 26) mutations associated congenital hearing loss and epistaxis (control). The survey included questions regarding symptoms of torticollis, vertigo, and hearing loss. Results: Patients with EVA had a 10-fold greater odds of having torticollis than controls (31% vs. 4%; OR = 10.6; 95% CI: 2.9, 39.2). No patients with GJB2 had a reported history of torticollis. Torticollis preceded the diagnosis of hearing loss in most (87%) patients with EVA who had a reported history of torticollis. EVA patients were more likely to have reported motor delay than controls (40% vs. 15%; p = 0.002). EVA patients with prior torticollis (80%; 12/15) were more likely to have balance impairment than EVA patients without prior torticollis (12%; 4/33; p < 0.001). Twelve patients had a reported history of paroxysmal torticollis, all of whom had EVA. Conclusion: Torticollis in infants may be a marker of EVA. Infants with torticollis should be monitored closely for hearing loss and motor delay, especially when the torticollis is paroxysmal.
1. Introduction Approximately 5 out of every 1000 children in the United States have a unilateral or bilateral moderate to profound hearing loss [1], but less than half are detected or present at the time of newborn hearing screening [2]. Up to 16% of cases of sensorineural or mixed hearing loss in children are associated with enlarged vestibular aqueducts (EVA) [3]. EVA is the most common structural temporal bone anomaly associated with congenital hearing loss [4]. Up to half of patients with EVA have either one or two mutant alleles of the SLC26A4 gene, which causes both Pendred syndrome and non-syndromic recessive hearing loss (DFNB4) [5]. The reported incidence of vestibular dysfunction in patients with EVA varies widely in the medical literature, with some of the larger published series reporting rates of vestibular symptoms between 4 and 47% [4,6,7]. The hearing loss in EVA varies in its clinical presentation, with some cases being stable over time, while others are fluctuating and/or progressive [4]. Therefore, hearing loss may not be
detected on newborn hearing screens or may not be present at birth in 30–60% of patients with EVA. Early identification and close audiologic monitoring is particularly important in patients with EVA, due to the high incidence of sudden and/or progressive hearing loss in many affected children. Torticollis is a persistent tilting of the head with rotation of the chin toward the contralateral shoulder, which results from contraction of the ipsilateral sternocleidomastoid muscle. Torticollis most commonly presents in infancy and can be either chronic or paroxysmal (intermittent). Chronic torticollis most commonly presents at birth (congenital torticollis) with an estimated prevalence between 0.3 and 2% [8]. It may present with a palpable mass in the sternocleidomastoid muscle that can be seen on imaging studies, which is known as fibromatosis colli. Most cases of congenital torticollis will resolve spontaneously or following a course of physical therapy. Other common causes of chronic torticollis in infants and young children include oculomotor disorders (e.g. strabismus, congenital nystagmus) and
∗ Corresponding author. Department of Otolaryngology and Communication Enhancement, Boston Children's Hospital, 300 Longwood Ave, Boston, MA, 02155, USA. E-mail address: [email protected] (J.R. Brodsky). 1 Present address: Vanderbilt University School of Medicine, 1161 21st Ave S, Nashville, Tennessee 37232, U.S.A. 2 Present address: Harvard Medical School, 243 Charles Street, Boston, MA 02114, U.S.A.
https://doi.org/10.1016/j.ijporl.2020.109862 Received 10 September 2019; Received in revised form 7 December 2019; Accepted 5 January 2020 Available online 07 January 2020 0165-5876/ © 2020 Published by Elsevier B.V.
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since birth). Subjects were categorized as experiencing “other” torticollis if torticollis symptoms did not meet these criteria, or if data on age of onset or frequency of episodes was incomplete. Patients with a reported history of nystagmus, strabismus, and/or eye surgery were excluded from the analysis to avoid inclusion of patients with torticollis of ophthalmologic origin. We performed an initial power analysis to determine needed sample sizes to achieve 80% power to detect a difference in the prevalence of prior history of torticollis by at least 20% between two groups, assuming a two-sided significance level of α = 0.05. This analysis yielded ideal sample sizes of 49 patients with EVA and 70 patients with epistaxis. We compared the prior history of torticollis between EVA patients and healthy controls using Fisher's exact or Chi-square test. Odds Ratio (OR) and 95% confidence interval (CI) were computed for the association between torticollis and EVA. Similarly, we compared motor delay, vertigo, and balance impairment between EVA patients and healthy controls. All statistical analyses were performed by a statistician using Statistical Analysis Software (SAS, Cary, NC).
plagiocephaly. Paroxysmal torticollis is typically attributed to vestibular dysfunction in young children, and has primarily been described in the setting of benign paroxysmal torticollis of infancy (BPTI), which is a condition primarily affecting infants and young children characterized by recurrent episodes of torticollis lasting for hours to days [9–12]. These episodes recur at a variable frequency, ranging from weeks to months between episodes. Several studies have found a link between BPTI and migraine, with 43–80% of BPTI patients having a family history of migraine [11,13–15]. We have observed a particularly high incidence of both chronic and paroxysmal torticollis in children with hearing loss associated with EVA. Our aim in this study was to determine if torticollis occurs at a higher rate in infants with hearing loss and EVA compared to children with hearing loss unrelated to EVA and to normal hearing controls. 2. Materials and methods 2.1. Participants
3. Results
We reviewed our internal databases of patients seen in the Balance and Vestibular Program and in the Hearing Loss Clinic at Boston Children's Hospital to identify patients seen by the junior (JB) or senior (MK) authors from January 2011–March 2017 that were given a diagnosis of EVA or hearing loss associated with biallelic GJB2 mutations. The GJB2 group served as a hearing loss control group, to help in differentiating whether torticollis is specifically associated with EVA or more generally with congenital hearing loss. Diagnosis of EVA was determined by radiologic criteria [16]. We also used outpatient billing records to identify patients seen over the same time period for evaluation of epistaxis, which were included as a control group. The absence of a recorded history of hearing loss in the control group patients was confirmed by medical record review, and all patients included in the study had undergone newborn hearing screening. Only patients who were ≤18 years of age at the time of diagnosis of torticollis, hearing loss, or epistaxis were included in the study.
3.1. Patient characteristics The study included forty-eight patients with EVA, 12 patients with biallelic GJB2 mutations, and 73 patients with epistaxis (healthy control group). An additional fourteen patients were excluded from the analysis due to a reported history of nystagmus, strabismus, and/or eye surgery. Mean age at the time of the survey was 9.3 (SD 4.6) years among patients with EVA, 11.1 (SD 4.6) years among healthy controls, and 6.7 (SD 4.1) years among patients with GJB2 mutations. Females made up 62% of the EVA group, 33% of the GJB2 mutation group, and 31% of the healthy control group, respectively. Among 48 patients with EVA, 23 patients had bilateral EVA and 25 patients had unilateral EVA. Mean age at initial hearing loss diagnosis was 3.0 (SD 2.6) years (range: 0–8 years). Seven patients in the EVA group reported a history of an abnormality in the SLC26A4 gene, though further details on these mutations were not available for analysis, as they were self-reported by the families completing the survey.
2.2. Data collection We generated an online survey using REDCap (Research Electronic Data Capture) software [17], which included questions about any history of episodes of head tilting or vertigo along with the temporal features of these symptoms. The survey also included questions about general patient demographics, hearing loss, and whether patients had a history of balance impairment, motor delay, and/or eye/vision problems. The same questionnaire was used for all subjects, but the REDCap survey included branching logic to facilitate efficiency of completion. For example, questions about further details of head tilting episodes were excluded if a respondent denied a history of tilting episodes, altogether. Families of included patients were sent letters by mail describing the study and were given the opportunity to opt out via prestamped postcards. Those who did not opt out after a two week period were contacted by phone and verbally consented to participate in the survey with a research assistant, or completed the survey over a secure email link sent directly from REDCap. Patients who met inclusion criteria were also recruited in person when seen for a clinic visit with one of the participating study providers. These patients completed the survey in person with a research assistant after providing verbal consent to participate. Each participant's survey responses were linked only to their diagnosis group and not to their name or any other specific patient identifiers in order to maintain anonymity. This study was approved by the Institutional Review Board at Boston Children's Hospital.
3.2. Torticollis Patients with EVA had a 10-fold greater odds of having torticollis than healthy controls (31% vs. 4%; OR = 10.6; 95% CI: 2.9, 39.2; p < 0.001; Table 1). Of the 12 patients with GJB2 mutations, none had a reported history of torticollis (31% in EVA vs. 0% in GJB2; p = 0.027; Table 2). Thirty-five percent (8/23) of patients with bilateral EVA had a reported history of torticollis, compared to 28% (7/25) of patients with unilateral EVA. Mean age of onset of torticollis among EVA patients was 2.4 (SD 3.3) months, and age of resolution was 18.6 ( ± 13.8) months. Thirteen (87%) of the 15 EVA patients with a history of torticollis had a reported onset of torticollis prior to the diagnosis of hearing loss, with a mean age of torticollis onset of 2.3 months and a mean age of hearing loss diagnosis of 39.7 months (Fig. 1). The onset of torticollis preceded the diagnosis of hearing loss in those thirteen patients by a mean of 43.4 months (more than 3.5 years). In the EVA group, hearing loss was reported to have been diagnosed at birth in ten patients without torticollis (20.8%) and in only two patients with torticollis (4.2%). Seven patients in the EVA group (14.6%) had a reported history of an abnormality in the SLC26A4 gene on genetic testing, only one of whom reported a history of torticollis (chronic). Among all 133 patients included in the analysis, twelve (9%) patients had a reported history of paroxysmal torticollis, all of whom had EVA. Out of all patients with EVA in the study, 25% had a reported history of paroxysmal torticollis. No patients with GJB2 or epistaxis (control) had a reported history of paroxysmal torticollis. All EVA patients with a reported history of paroxysmal torticollis also reported that the episodes had resolved prior to the time of
2.3. Statistical analysis Torticollis was categorized as paroxysmal (≥4 episodes of torticollis) or chronic (single episode of torticollis or continuous torticollis 2
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Table 1 Reported prior history of torticollis, vertigo, balance impairment, and gross motor delay in patients with enlarged vestibular aqueduct (EVA) compared to patients with epistaxis (control group).
Torticollis Paroxysmal torticollis Chronic torticollis Age of torticollis onset, months, mean (SD) Age of resolution, months, mean (SD) Vertigo Balance impairment Gross motor delay
EVA (n = 48)
Control (n = 73)
OR (95% CI)
p-value
15 (31%) 12 (25%) 3 (6%) 2.4 ( ± 3.3) 18.6 ( ± 13.8) 13 (27%) 16 (33%) 19 (40%)
3 (4%) 0 (0%) 1 (1%) 2.2 ( ± 3.8) 5.5 ( ± 3.5) 4 (5%) 6 (8%) 11 (15%)
10.6 (2.9, 39.2)
< 0.001
6.4 (1.9, 21.1) 5.6 (2.0, 15.6) 3.7 (1.6, 8.8)
0.002 < 0.001 0.003
EVA patients with torticollis (80%; 12/15) were more likely to have balance impairment than EVA patients without torticollis (12%; 4/33; p < 0.001). There was not a statistically significant difference in reported rates of gross motor delay, vertigo, or imbalance between the EVA and GJB2 groups (Table 2).
Table 2 Reported prior history of torticollis, vertigo, balance impairment, and gross motor delay in patients with enlarged vestibular aqueduct (EVA) compared to patients with GJB2-related hearing loss (“hearing loss control group”). EVA (n = 48)
GJB2 (n = 12)
OR (95% CI)
p-value
Torticollis Paroxysmal torticollis Chronic torticollis Vertigo Balance impairment
15 (31%) 9 (19%) 4 (8%) 13 (27%) 16 (33%)
0 0 0 2 2
–
0.027
Gross motor delay
19 (40%)
3 (25%)
(0%) (0%) (0%) (17%) (17%)
4. Discussion 2.5 (0.5, 12.8) 2.0 (0.5, 8.2)
0.71 0.32
Hearing loss has major implications for young children, but its identification may be delayed in children with a later onset hearing loss that was either absent at birth or was mild enough initially to be undetected on a newborn hearing screen, both of which are often the case with EVA. The observation in this study of a higher reported incidence of torticollis in babies with EVA may aid clinicians in the early detection of EVA-related hearing loss. Enlargement of the vestibular aqueducts was originally described by Mondini in 1791 in temporal bone specimens in conjunction with other anatomic anomalies of the cochlea that are seen in conjunction with EVA in some affected patients, including a cochlea with only 1.5 turns instead of the usual 2.5 turns as well absence of the interscalar septum between the middle and apical turns [4]. Recently, a new classification system for the radiologic patterns of inner ear malformations was defined by Sennaroglu and Saatci, which has become the standard approach for radiographically describing such anomalies [18]. Part of this classification includes two incomplete partition (IP) anomalies. Incomplete partition type II (IP-II) is the current terminology used to
0.51
survey completion. The mean reported age of paroxysmal torticollis resolution was 1.61 ( ± 1.34) months of age. 3.3. Motor delay, vertigo, and balance impairment Motor delay was reported in a significantly higher proportion of patients in the EVA group (40%) than in the control (epistaxis) group (15%; OR = 3.7; 95% CI: 1.6, 8.8; Table 1). Patients with EVA were more likely to experience vertigo (27%) or balance impairment (33%) than in the healthy control group (5% for vertigo and 8% for balance impairment). EVA patients who had a reported history of torticollis were more likely to also have reported motor delay (67%; 10/15) than EVA patients without torticollis (27%; 9/33; p = 0.01). Additionally,
Fig. 1. Age of onset of torticollis and hearing loss in fifteen children with enlarged vestibular aqueduct and associated hearing loss and torticollis. Torticollis onset preceded hearing loss onset in all but two patients. 3
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3.5–60 months) [11]. Many possible mechanisms have been proposed for the pathogenesis of BPTI, but none have been definitively established. The findings in our study suggest that many cases of paroxysmal torticollis in infants may be related to EVA instead of to BPTI. A quarter of EVA patients in our study group reported a history of paroxysmal torticollis, while none of the patients in the other groups had a reported history of paroxysmal torticollis. In 1969 Snyder and colleagues did propose that BPTI might be a form of labyrinthitis, due to the frequent association with other vestibular symptoms and the presence of three patients with hearing loss out of 12 patients with BPTI in their study [24]. One other study also recently described one patient with hearing loss of unknown etiology out of three patients with BPTI [10]. Not all patients in these studies had audiometry, and follow-up was also limited, so some cases of hearing loss may not have been identified. Only two EVA patients in our study with a reported history of torticollis (one paroxysmal and one chronic) had been diagnosed with hearing loss at birth, while none of the other ten EVA patients that were diagnosed with hearing loss at birth had reported torticollis. A theory that we propose for this phenomenon is that the torticollis episodes in infants with EVA may actually represent early signs of a progressively failing inner ear, while those with hearing loss at birth may not have torticollis episodes as the inner ear impairment has already stabilized. Another observation in support of this theory is that all seven patients with a reported history of abnormalities on SLC26A4 testing also had no history of paroxysmal torticollis symptoms. Some studies have found EVA patients with homozygous SLC26A4 gene mutations to have more severe hearing loss at an earlier average age, while EVA patients without SLC26A4 mutations are more likely to have more progressive and/or fluctuating hearing loss over time [5,25,26]. It is possible that a similar phenomenon may occur with the vestibular system of patients without SLC26A4 mutations, though further study with more objective determination of SLC26A4 mutation status in a larger number of patients would be needed to determine whether or not this is the case. The relationship between torticollis and vestibular dysfunction in EVA patients is further supported by the fact that no patients in the GJB2 group had reported torticollis, though it should be noted that there are reports of vestibular dysfunction in GJB2 patients, although at a much lower rate than with EVA [27]. We also found a significantly higher incidence of motor delay in the EVA group compared to the control group. Other studies have reported a high incidence of motor delay in children with EVA [6,7,28], which has been attributed to vestibular impairment [29–31]. We found a significantly higher rate of reported balance impairment in children in the EVA group who had a history of paroxysmal torticollis compared to those who did not. This supports a connection between paroxysmal torticollis in EVA patients and progressive vestibular loss. Based on this finding we recommend that infants with torticollis, especially those with paroxysmal torticollis, be screened early and monitored carefully for balance impairment and motor delay, so that physical therapy services can be initiated early enough to minimize delays when they begin to appear. A limitation of this study is the potential for recall bias due to the
describe what was previously referred to as the Mondini malformation. Valvasori and Clemens described the association between EVA and hearing loss in 1978 in 50 out of 3700 computerized tomography (CT) scans, which they used to establish the original radiologic criteria for the diagnosis of EVA [16]. Since that time a number of different radiologic measurements have been described for establishing the diagnosis of EVA, though currently the most commonly used criteria are those established in 2007 at Cincinnati Children's Hospital [19]. EVA can be either sporadic or can be associated with mutations in the SLC26A4 gene encoding the anion exchange protein pendrin, which can result in Pendred syndrome (EVA, hearing loss and thyroid dysfunction) or in nonsyndromic recessive deafness (hearing loss and EVA only; DFNB4) [5]. The mechanism behind the relationship between EVA and torticollis is not clear, though it is most likely related to dysfunction of the vestibular system. Torticollis is a common symptom of vestibular dysfunction in young children, which may be a response mediated by the vestibulo-colic reflex, which originates in the saccule organ of the vestibular labyrinth and affects the tone of the sternocleidomastoid muscle. This response is often abnormal in patients with EVA, resulting in abnormal cervical vestibular evoked myogenic potential testing, which may indicate dysfunction at the level of the saccule in these patients [20]. We have had the opportunity to observe a number of our own EVA patients during head tilting episodes, either in person or through parent-provided videos. We have found that they typically demonstrate a rotation of the chin to the opposite side of the head tilt consistent with contraction of the sternocleidomastoid muscle, as is seen in true torticollis. This is in contrast to a head tilt that would be seen from a skewed perception of the visual vertical. Many patients with EVA have vestibular symptoms and abnormalities on vestibular testing, though the incidence of vestibular dysfunction in EVA varies widely between studies [4,6,7]. In a 2015 prospective cohort study of 106 patients with EVA, Zalewski and colleagues reported that 44% of EVA patients had vestibular symptoms, and 45% had abnormalities on videonystagmography [6]. They also reported that 20% of EVA patients had reported a history of head tilting and vomiting at a prelingual age. This is the only prior report that we have been able to identify in the medical literature of an association between torticollis and EVA, though paroxysmal torticollis was not specifically described in that study and no specific details were provided on the head tilting beyond its reported incidence in the cohort. Additionally, Lu and colleagues did describe paroxysmal torticollis in a SLC26A4 knock-out mouse model [21]. Although chronic, congenital torticollis is quite common [22], the phenomenon of paroxysmal torticollis is more unusual and is of particular interest, since it occurred in 9% of patients in our study, all of whom had EVA. In the medical literature, paroxysmal torticollis has ubiquitously been attributed to BPTI, which is generally considered to be a migraine precursor disorder. The diagnostic criteria for this disorder are outlined in Fig. 2 [23]. Accompanying symptoms can include vomiting, irritability, ataxia, malaise and pallor, though often torticollis is the only evident symptom. A systematic review of 109 cases of BPTI from our program reported a mean age of onset of 5.9 months (range: 1 week–30 months) and a mean age of resolution of 31.4 months (range:
Fig. 2. Diagnostic Criteria for Benign Paroxysmal Torticollis of Infancy as outlined in the International Classification of Headache Disorders, 3rd edition. 4
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retrospective survey format. Mean ages in the EVA and control (epistaxis) groups were higher than in the GJB2 group at the time of the study, so parental recall of infantile symptoms may have been less accurate in the older groups. Also, there were more females in the EVA group than in the other groups, which could have impacted the relative incidences of torticollis in the groups. A prospective cohort study of torticollis in EVA patients and its relationship to motor development and vestibular function is warranted.
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5. Conclusions The results from this study suggest that torticollis is more common in infants with EVA than in healthy controls or patients with non-EVA hearing loss, and may be an early marker of EVA, though further study of this relationship is warranted. Infants with paroxysmal torticollis or unexplained chronic torticollis may benefit from close audiological monitoring and motor screening. Pediatric providers may be able to use this approach to identify one of the most common causes of congenital hearing loss well before the hearing loss itself is evident, so that interventions for hearing loss and motor delay can be initiated as early as possible. Funding source All phases of this study were supported through internal funding provided by the Department of Otolaryngology and Communication Enhancement at Boston Children's Hospital. Meeting information The findings of this study were presented at the European Society of Pediatric Otolaryngology (ESPO) meeting in Stockholm, Sweden in June 2018. Declaration of competing interest None. Acknowledgement The authors would like to thank Alicia Wang, BS for her assistance in the preparation of this manuscript. References [1] C.A. Boyle, S. Boulet, L.A. Schieve, R.A. Cohen, S.J. Blumberg, M. Yeargin-Allsopp, et al., Trends in the prevalence of developmental disabilities in US children, 19972008, Pediatrics 127 (2011) 1034–1042. [2] A. Erenberg, J. Lemons, C. Sia, D. Trunkel, P. Ziring, Newborn and infant hearing loss: detection and intervention.American academy of pediatrics. Task force on newborn and infant hearing, 1998- 1999, Pediatrics 103 (1999) 527–530. [3] D.A. Preciado, L. Lawson, C. Madden, D. Myer, C. Ngo, J.K. Bradshaw, et al., Improved diagnostic effectiveness with a sequential diagnostic paradigm in idiopathic pediatric sensorineural hearing loss, Otol. Neurotol. 26 (2005) 610–615. [4] Q. Gopen, G. Zhou, K. Whittemore, M. Kenna, Enlarged vestibular aqueduct: review of controversial aspects, The Laryngoscope 121 (2011) 1971–1978. [5] J. Rose, J.A. Muskett, K.A. King, C.K. Zalewski, P. Chattaraj, J.A. Butman, et al., Hearing loss associated with enlarged vestibular aqueduct and zero or one mutant
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