15 Congenital and Pediatric Vestibular Disorders

A wide prevalence range (0.45–15.0%) is reported for dizziness in the pediatric population. The variation can be attributed to different inclusion criteria and varying data collection methods (chart review versus survey results) as well as the difficulty of characterizing symptoms in this population.1,2,3 Disorders common in the adult population (benign paroxysmal positional vertigo [BPPV] and Meniere’s disease) are uncommon in children. In contrast, some diseases seen in children (benign paroxysmal vertigo) are relatively unheard of in adults. The following is a brief account of congenital and pediatric vestibular abnormalities.

Embryology of the Vestibular System

It is important to understand the embryologic development of the vestibular system and how various insults to this process result in vestibular dysfunction. The development of the inner ear begins at approximately the third week of gestation, earlier than that of the middle and external ear. It starts with the formation of the otic placode on the lateral surface of the neural tube.^4,5 Gradual invagination of the otic placode to form the otic pit and then the otocyst occurs during the fourth week. As development enters the fifth week, otocyst folds begin to give rise to the primordial cochlea/saccule ventrally, the utricle/vestibule dorsally, and the endolymphatic sac/duct. Elongation and helical formation of the cochlea to its full two and three-quarter turns occurs in the sixth through tenth weeks. The round window and cochlea reach final size around 24 weeks.⁶ Three immature semicircular canals (SCCs) develop as half disks from the primordial vestibular portion. Mesenchyme then fills in the central core of the half disks to create well-differentiated SCCs. Richards et al postulate that the canals undergo a progressive unfolding process, reaching adult size by weeks 17 to 25 of gestation.^6,7 However, a recent imaging study of human fetuses found no correlation of the SCC angles with gestational age. The authors concluded the variation in SCC angles is an adaptation to physiologic vestibular function.⁸

Ossification of the otic capsule progresses from 14 ossification centers forming between weeks 16 and 21, with the SCCs ossifying relatively late in gestation.⁹ Ossification of the superior SCC occurs around 23 weeks, followed by the posterior and lateral canals, at 24 and 25 weeks, respectively.6 The last ossification center to form lies over the posterior SCC. Early histologic studies suggest isolated regions of incomplete ossification occur in up to 65% of fetal temporal bones and in children up to 3 years old, but no particular distribution was seen¹⁰ Thus, the vestibular labyrinth is completely formed by halfway through the second trimester, but full ossification with mineralized bone may continue until birth and even into infancy. Incomplete ossification may lead to apparent dehiscences in the SCC in pediatric patients, but the pathophysiology and clinical significance of pediatric SCC dehiscence is not well understood. Chen et al reviewed 131 pediatric CT scans and found an incidental 14% dehiscence rate among patients with hearing loss.¹¹ The majority involved the superior canal (14 patients) and the remaining involved the posterior canal. If dehiscence is caused by arrested development, one would expect defects in the lateral SCC to be common, yet this has not been the case. Chen et al did find threefold higher rates of posterior SCC dehiscence in a pediatric population than were found in a recent study including adults by Russo et al.^11,12 Of interest, Chen et al did not find a correlation between the CT findings and either hearing results or symptoms. Thus, the pathophysiology and clinical significance of the developmental variations remain unclear.

The vestibular aqueduct, a bony canal extending from the vestibule to the sigmoid sinus, encloses the endolymphatic sac, a small artery, and a vein. It has been theorized that the canal is proportionately larger in early development, with decrease in size of the vestibular aqueduct as the inner ear continues to mature, but more recent studies present conflicting data.⁵ Pyle studied the histopathology of 48 developing temporal bones, measuring various points of the vestibular aqueduct during development. He found continued nonlinear growth throughout embryonic life, which contradicts the theory that enlarged vestibular aqueduct syndrome originates from arrested prenatal development.¹³

Although the bony labyrinth is formed early in gestation, the vestibular ganglion cells continue to remodel and mature throughout fetal development. They are present in various shapes after 13 weeks of gestation, reaching a uniform shape at 24 weeks, with continued development until 39 weeks. They are thought to reach maturity around birth.¹⁴ Myelination begins around week 20 of gestation and continues until puberty.¹⁵ Therefore, neonatal and pediatric vestibular reflexes are in varying stages of development and need to be interpreted with appropriate reference standards.

Clinical Evaluation of Congenital and Pediatric Vestibular Disorders

History and Physical Exam

A comprehensive history and physical exam are critical to ascertaining the correct diagnosis of pediatric patients with vestibular dysfunction. Young patients may have great difficulty describing their symptoms. The onset, progression, and timing of symptoms are important features to note. The clinician should ask about aggravation of vestibular symptoms in response to minor head trauma or loud sounds. Additionally, vestibular symptoms may be associated with an increase in hearing loss, tinnitus, headaches, seizures, and other associated ear symptoms that may be difficult for a young person to relate. A vestibular anomaly could be masked as general clumsiness and delay presentation for years; therefore, specific note of the age of ambulation should be made. Delayed onset of ambulation beyond 18 months of age should be considered abnormal and may be an indicator of early vestibular disease. Vestibular dysfunction may be induced by recent infections or various toxic insults, and thus it is critical to ask about infections or exposure to ototoxic medications. Congenital infections, such as toxoplasmosis, syphilis (other), rubella, cytomegalovirus, and herpes (TORCH), may hinder development.

The evaluation should also include a thorough history to search for accompanying characteristics of hereditary syndromes. Examples of this would be night-blindness (Usher’s syndrome), family history of male-only involvement (X-linked deafness with perilymphatic gusher), and family history of a white forelock (Waardenburg’s syndrome). If the history includes hereditary features, construction of a family pedigree is the next step in the diagnostic process.

A comprehensive physical exam is essential. The exam typically starts with micro-otoscopy with pneumatic insufflation. The examiner should observe for vertigo or nystagmus (Hennebert sign) during pneumatic otoscopy. Testing for Tullio phenomenon (vertigo in response to a loud sound) may be performed with a Barany noise box or tuning fork. Additionally, a complete head and neck exam, eye exam, and cranial nerve exam need to be performed. A full-body exam should be performed to search for any dysmorphic features. The child’s cardiopulmonary condition should be assessed and abnormal musculoskeletal findings that may cause unsteadiness and gait disorders should be evaluated.

The vestibular system should be evaluated with consideration for developmental milestones. Clearly, there are age-related limitations to the vestibular exam. The exam can be tailored to each child’s ability and willingness to follow instructions and ambulate. The vestibular exam of an infant requires some specific exam techniques. Extraocular movements and gaze-evoked nystagmus can be assessed in a small child by using a small toy to draw the child’s attention to the four visual quadrants (Fig. 15.1).

The presence of an intact vestibulo-ocular reflex (VOR) may be assessed in an infant by holding the child at arm’s length and spinning in circles (Fig. 15.2; Video 15.1). At less than 3 weeks of age, the eyes will deviate away from the direction of acceleration (“doll’s eye” phenomenon), but by 3 weeks of age, the eyes should deviate toward the direction of acceleration, as would an adult’s eyes. This doll’s eye phenomenon may persist in premature infants for up to 3 months. Other inherent reflexes, such as the Moro reflex, parachute reflex, and righting reflex, may also be helpful in evaluating the infant’s neurologic development. The presence of the VOR may also be elicited in older children by spinning them in the exam chair for 20 to 30 seconds and looking for normal postrotary nystagmus.

If possible, the full exam, including gait, Fukuda stepping test, eyes-closed Romberg, tandem Romberg, tandem gait, cerebellar testing, and positional testing, should be performed. There are no clearcut normative data for these clinical examination findings in young children; however, some general age-related milestones are important to consider. Children should be able to ambulate by 18 months of age. By 5 years of age, most children should be able to walk a straight line with minimal errors, but even 7-year-olds may have a few errors on this task. Most school-age children will be able to maintain an eyes-closed Romberg for 15 seconds and a tandem Romberg for 6 seconds (Fig. 15.3; Video 15.2).

The balance exam in older children may be augmented with the use of a foam pad.¹⁶ Specific physical findings, such as post-head-shake nystagmus and head thrust exam, may be helpful in detecting vestibular weakness. The Bruininks-Oseretsky Test of Motor Proficiency, second edition (BOT-2) includes a subtest for balance with normative data down to 4 years of age. The test scores a series of tasks (Table 15.1; Video 15.3) and then applies an age adjustment for a final score. Such quantitative assessment is critical for research studies and similar assessment tools may be useful in practice.

Additional audiometric and vestibular testing should be tailored to each child. Age-appropriate audiologic evaluation is required in every patient. In selected patients, the examination can be further augmented with videonystagmography to search for vestibular loss or hypofunction. The VOR is responsive at birth and continues to mature over the first few years of life. Caloric testing is possible at 2 months of age but is often poorly tolerated in the pediatric population.¹⁷ The cervical vestibular evoked myogenic potential (cVEMP) test can also be used to evaluate saccular function. Although there are some limitations (infants are unable to maintain muscle contraction with head elevation), cVEMPs have been used in newborns and pediatric patients.^15,18,19 Posturography may be helpful, but it is important to note that the vestibular system is not fully developed until age 12, and therefore pediatric normative data are not available.^15,20

Fig. 15.1 Evaluation of extraocular movements in an infant.

In general, imaging studies should be reserved for vertiginous children with other neurologic symptoms, focal neurologic signs, unilateral hearing loss, or severe disease. Imaging studies are costly and frequently require sedation in the pediatric population; therefore, careful consideration is required in each case. Niemensivu et al studied imaging findings in vertiginous children.21 Out of 23 children with new deviant neurologic findings, 22 children (96%) had associated severe headache or neurologic findings on exam. They concluded that imaging should not be performed in vertiginous patients without other neurologic findings.²¹

Fig. 15.2 In-office rotatory testing of an infant/child.

Fig. 15.3 Vestibular testing of the school-age child (BOT-2 exam).

Patients with congenital vestibular dysfunction may present with minimal symptoms or balance deficits due to central nervous system (CNS) compensation and use of somatosensory visual information.22 Phenotypic expression may therefore be masked by individual compensatory abilities. Enbom et al evaluated 18 children with congenital or early acquired bilateral vestibular loss. Six of these patients had Usher’s syndrome, with two other patients having unspecified hereditary hearing loss. Testing with eyes closed showed no significant difference in body sway velocity until the somatosensory information was perturbed. This study suggested that patients with congenital vestibular anomalies use anticipatory mechanisms in posture and balance to perform similar to controls in most everyday situations.²²

Congenital Vestibular Disorders

Congenital Syndromes

Waardenburg Syndrome

Waardenburg syndrome is inherited in an autosomal dominant pattern and has been linked to six different genes, including PAX3, MITF, EDN3, EDNRB, SOX10, and SNAI2.²³ Incidence of Waardenburg syndrome is estimated to be between 1 in 10,000 and 1 in 20,000.²⁴ The syndrome is characterized by heterochromia iridis, white forelock, dystopia canthorum (type I), synophrys, hypopigmented areas of the skin, congenital sensorineural hearing loss (SNHL), and hypotrophic nasal alae. There are isolated reports of vestibular anatomic abnormalities, including malformation or absence of the semicircular canals, as well as hypoplasia of the cochlea.^25,26,27 However, a recent review by Kontorinis et al found no abnormalities on the high-resolution computed tomography (CT) scans of 20 patients.²³

Table 15.1 Components of the Bruininks-Oseretsky Test of Motor Proficiency, second edition (BOT-2), balance subtest

The vestibular findings in Waardenburg syndrome are as variable as the expression of the other phenotypic abnormalities. Black et al found vestibular symptoms to be the most common chief complaint in 22 patients with Waardenburg syndrome.28 Sixteen patients (73%) had complaints of either disequilibrium or vertigo and 17 patients (77%) had abnormal vestibular function tests. Interestingly, the authors found no differences in vestibular findings based on Waardenburg subtype and noted that vestibular symptoms may be the presenting complaint, even in the absence of hearing loss.²⁸ Similarly, Marcus et al reported high rates of vestibular dysfunction (21 of 22 subjects) in a study of a family with Waardenburg syndrome.²⁵

Branchio-Oto-Renal Syndrome

Branchio-oto-renal (BOR) syndrome is an autosomal dominant disorder of the first and second branchial arches, with causative genes including EYA1, SIX1, and SIX5. Its prevalence has been reported at 1 in 40,000.²⁹ BOR syndrome is characterized by hearing loss, malformation of the auricles, preauricular pits, renal anomalies, and branchial cleft fistulas. Hearing loss may be mixed, conductive, or sensorineural. Vestibular findings include unsteadiness in dark environments and delays in ambulation as long as 22 months.³⁰ Radiographic inner ear malformations are variable. Chen et al looked at temporal bone scans of 12 patients with BOR syndrome and found 11 of 24 ears with enlarged vestibular aqueducts, four enlarged vestibules, and three hypoplastic horizontal semicircular canals.³¹ Ceruti et al preformed a review of eight patients in one family and noted abnormal lateral semicircular canals in 14 of 16 ears, and five ears with an enlarged vestibular aqueduct.³² Despite BOR syndrome’s being commonly associated with inner ear malformations, vestibular dysfunction is not well studied in these patients.^31,32,33 There are case reports of hyporeflexia and areflexia on vestibular testing, but no large-scale investigations.^30,34

Neurofibromatosis Type 2

Neurofibromatosis type 2 (NF2) is an autosomal dominant disorder with a prevalence of 1 in 100,000.³⁵ It is characterized by multiple nervous system tumors, including bilateral vestibular schwannomas, ocular abnormalities, and skin abnormalities. Although the syndrome is defined by vestibular schwannomas and hearing loss is a common finding, vestibular dysfunction is not commonly a presenting symptom. Choi et al looked at 26 pediatric NF2 patients and found only 20% with vestibular symptoms at the time of diagnosis, presumably due to slow tumor growth.³⁶ Nunes and MacCollin looked at 12 patients with NF2 and found 25% with abnormal ambulation.³⁷

Usher’s Syndrome

Usher’s syndrome is a rare autosomal recessive syndrome characterized by SNHL, retinitis pigmentosa, and variable presence of vestibular dysfunction.^38,39,40 The prevalence rate is reported to be 3.5 to 6.2 per 100,000.^41,42 Thus far, 11 distinct loci have been discovered related to the syndrome and more overlap is being found between different subtypes.⁴² Classically, Usher’s syndrome is classified into three main categories based on clinical findings, but genetic advances are allowing for atypical subtypes and further differentiation within the classes.

Type I is characterized by profound deafness, vestibular dysfunction, and early onset of progressive retinitis pigmentosa starting before puberty. Delayed age of ambulation is a frequent finding in this subtype.³⁹ Vestibular abnormalities of Usher’s type IB are described as “vestibulocerebellar ataxia” due to the radiographic finding of cerebellar abnormalities.⁴³ Although cochlear abnormalities have also been reported, radiographic imaging of the inner ear is typically normal.^26,44 As a result, there is controversy whether the vestibular dysfunction is central or peripheral in origin. Usher’s type II is the most common form and is associated with moderate to severe congenital deafness with normal vestibular dysfunction and retinitis pigmentosa beginning in the teenage years.

Type III has variable progressive hearing loss, later onset of retinitis pigmentosa, and variable vestibular dysfunction.⁴⁵ Type III is comparatively rare except in Ashkenazi Jewish families.⁴¹ Sadeghi et al studied vestibular function in patients with USH3 mutation and found 19 of 22 subjects reported walking prior to 18 months. Interestingly, vestibular testing of these adults revealed vestibular hypofunction or areflexia in ten subjects (45%), leading the authors to conclude that some of the patients suffered from a progressive vestibular loss.

Pendred’s Syndrome

Pendred’s syndrome is an autosomal recessive disorder characterized by profound symmetric SNHL, goiter, and enlarged vestibular aqueduct (Fig. 15.4). It is commonly associated with the SLC26A4 gene.⁴⁶ Luxon et al studied vertiginous signs and symptoms and radiographic findings in 33 patients with Pendred’s syndrome and profound hearing loss, the vast majority of whom had bilateral dilated vestibular aqueducts.⁴⁷ Fifteen of 33 subjects complained of dizziness or vertiginous symptoms. Vestibular testing demonstrated one-third of patients with normal responses, one-third with unilateral vestibular weakness, and one-third with bilateral vestibular deficits. No correlation was found between the degree of hypofunction and either the degree of hearing loss or the presence of an enlarged vestibular aqueduct.⁴⁸ In a study of patients with enlarged vestibular aqueducts, Miyagawa et al report on a subset of 15 subjects with Pendred’s syndrome,⁴⁹ 87% of whom had progressive hearing loss and 80% of whom suffered vertiginous symptoms. Vestibular dysfunction is a common complaint in patients with Pendred’s syndrome and should not be overlooked.

Jervell and Lange-Nielsen Syndrome

Jervell and Lange-Nielsen syndrome (JLNS) is a rare autosomal recessive syndrome characterized by prolongation of QT interval, childhood cardiac events, and congenital profound SNHL.^50,51 Incidence has been reported as 1.6 to 6 per 1,000,000.⁵¹ JLNS has been linked to the KCNQ1 gene, which encodes a potassium ion channel found in epithelial, cardiac, and gastrointestinal tissue, as well as in the inner ear. Winbo and Rydberg evaluated 14 patients with JLNS for vestibular dysfunction.⁵⁰ Gross motor developmental delay was reported in 11 out of 12 patients (92%). Postrotary nystagmus test was pathologic in nine patients evaluated, but testing was limited due to fear of provoking a cardiac event.⁵⁰ Currently, there are limited data in the literature and more research is needed to better characterize the vestibular dysfunction in JLNS.

Fig. 15.4 Enlarged vestibular aqueduct.

This disorder is classically described as bilateral mixed hearing loss and stapes fixation seen only in the males of a family.52 Bulbous internal auditory canal and incomplete separation of the bone from the base of the modiolus to the coils of the cochlea have been noted radiographically. POU3F4 mutations are the underlying cause in 60% of cases.⁵³ The disorder affects not only males, but also females, who may have moderate hearing loss. Vestibular abnormalities are variable. They may be unilateral or bilateral, and they are not associated with the degree of hearing loss. Although female carriers may demonstrate hearing loss, vestibular deficits have not been described in these patients.⁵² Cremars et al published a study of vestibular function in eight males from one family.⁵⁴ Responses to caloric stimulation were variable, including normal, unilaterally weak, and bilaterally weak responses. The one consistent finding for all affected males was a shortened decremental time constant of postrotary nystagmus.

CHARGE Association

Vestibular dysfunction is a key feature in CHARGE association and can be demonstrated clinically, radiographically, and on vestibular function testing. CHARGE association is an autosomal dominant disorder named for the combination of clinical features that are frequently associated: C oloboma, H eart defects, A tresia choanae, R etarded growth/development, G enital hypoplasia, and E ar abnormalities. The prevalence is estimated to be 1 in 8,500.⁵⁵ Diagnostic criteria have been updated to include cranial nerve dysfunction and hypoplasia of the semicircular canals.⁵⁶ CHARGE association is often a result of CDH7 gene mutations, which have been directly linked to vestibulocochlear defects.⁵⁶

CHARGE is associated with high rates of vestibular developmental abnormalities often detected on imaging and associated reports of balance dysfunction. Radiographic analysis by Morimoto et al of the CT scans of 13 patients with CHARGE association showed all had absence of semicircular canals (Fig. 15.5) and 19% had enlarged vestibular aqueducts, and 58% of vestibules were hypoplastic or dysplastic.⁵⁷ Similarly, Abadie et al conducted a prospective study of 17 children with CHARGE association and found semicircular canal abnormalities in 94%. In addition to radiographic findings, Abadie et al observed clinically correlated vestibular dysfunction in the patients. They reported milestones were consistently achieved an average of 50% later than normal controls, with 16 of 17 children not walking until after 18 months.⁵⁸

Vestibular testing in patients with CHARGE association is almost uniformly abnormal.^58,59 Murofushi and Graham reported all five CHARGE patients studied demonstrated absent vestibular responses on vestibulo-ocular reflex (VOR) testing and delayed motor development.⁵⁹ Deprivation of visual environment led to severe imbalance. Wiener-Vacher et al performed vestibular function tests on seven patients with CHARGE and found universally absent earth-vertical axis rotation (EVAR) responses (consistent with the finding of canal aplasia), with globally normal off-vertical axis rotation (OVAR) responses. They concluded that there was no canal VOR in any patients, but otolith VOR was present and close to normal throughout.⁶⁰

Enlarged Vestibular Aqueduct

Enlarged vestibular aqueduct (EVA) is a sporadic finding in most patients, but it also may be associated with other inner ear malformations or congenital syndromes, such as Pendred’s, Waardenburg, distal renal tubular acidosis, X-linked congenital mixed deafness, BOR syndrome, or CHARGE association.^27,61 Its occurrence ranges from 1 to 12% of patients with SNHL.⁶² Genetic abnormalities have been linked to several genes. Miyagawa et al studied patients with bilateral enlarged vestibular aqueducts in a Japanese population and discovered SLC26A4 mutation in 82% and GJB2 mutations in 8.7%.⁴⁹ Their finding of a high prevalence of the SLC26A4 mutation was consistent with other reported values for eastern Asian populations and is significantly higher than the prevalence in Caucasoid populations.⁴⁹

The diagnosis of EVA is defined by a diameter of greater than 1.5 mm at the midpoint of the postisthmic segment of the aqueduct or greater than 2 mm at the operculum (see Fig. 15.1). Characteristically, it is associated with down-sloping SNHL, but normal hearing to profound hearing loss has been reported, as well as a fluctuating, progressive, or sudden pattern of loss.^61,63 Progressive hearing loss is commonly believed to be associated with minor head trauma. Comparatively, vestibular symptoms are less common in EVA than hearing loss and have been reported between 4% and 48%.²⁷ The exact pathophysiology of vestibular dysfunction in these patients is unknown. The proposed pathologic mechanism is fluctuating transmitted intracranial pressure that affects the otolithic membrane. It is possible that the cochlea is more sensitive to pressure changes than the vestibular system. A second hypothesis is that hyperosmolar fluid refluxes into the cochlear duct, causing vertigo.⁶⁴

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