INTRODUCTION — Congenital anomalies result from errors in embryogenesis (malformations) or intrauterine events that affect embryonic and fetal growth (deformations and disruptions) [1]. The more complex the formation of a structure, the more opportunities for malformation.
The embryology, clinical features, and management of congenital anomalies of the ear are reviewed here. Many of these abnormalities are associated with hearing loss. The evaluation and management of hearing loss in children in discussed separately:
●(See "Screening the newborn for hearing loss".)
●(See "Hearing loss in children: Etiology".)
●(See "Hearing loss in children: Screening and evaluation".)
●(See "Hearing loss in children: Treatment".)
EMBRYOLOGY
Outer ear — The auricle or pinna is formed from the fusion of six raised soft tissue swellings (hillocks) on the surface of the embryo. Three of these hillocks are derived from the first branchial arch (Meckel) and three from the second branchial arch (Reichert) during the fifth and sixth weeks of intrauterine life. Growth of the fused tissues, guided by the pull of the intrinsic muscles of the ear, creates the folds of the helix, antihelix, and tragus (figure 1).
The ear canal is formed from an invagination of surface epithelium in the fifth week of intrauterine life. This was thought to represent a vestige of the first branchial cleft; however, fate mapping studies and evidence from transgenic mice with the duplicated auricular structures suggest instead that it results from a distinct invagination within the first branchial arch [2].
The solid core of cells meets a similar evagination from the pharynx, trapping a layer of mesothelium in between (figure 2). Fusion of these cells at the juncture results in the formation of the three layers of the tympanic membrane (figure 3). Recanalization of the external ear canal occurs in the second trimester and is complete at approximately 28 weeks gestation; vernix-like material is left behind [3].
Middle ear — The ossicles are formed by condensation of mesenchyme derived from the first and second branchial arches. Cartilage develops and gradually is replaced by bone in the second and third trimesters (picture 1). The ossicles are near adult size and adult ossification at the time of birth. Cartilage remains only at the articulations.
The cavity of the middle ear forms when endoderm evaginating from the first pharyngeal pouch invades the mesoderm of the middle ear. This pouch narrows to form the lining of the Eustachian tube near the nasopharynx and spawns fingerlike projections that surround the developing ossicles. The lateral-most projection of endoderm creates the inner layer of the tympanic membrane. Tympanic membrane retractions that cause cholesteatomas later in life follow the paths of these mucosal invaginations [4]. (See "Cholesteatoma in children".)
At birth, the middle ear is narrow and contains residual mesenchyme and amniotic fluid. Within minutes of birth and spontaneous breathing, air enters the Eustachian tube, displacing amniotic fluid to create a pneumatized cavity. Some mesenchyme persists beneath the mucosal of the middle ear for up to five years after birth [5].
Inner ear — Inner ear morphogenesis requires a highly coordinated and complex pattern of growth. The cochlea and vestibular system are derived from epithelium that migrates deep from within the embryonic surface early in development. This epithelium forms a fluid-filled cyst called the otic vesicle. The otic vesicle folds, spirals, and elongates to form the membranous labyrinth (picture 2). The otic vesicle divides into connected vestibular and cochlear parts in the fourth week of gestation. The developing cochlear parts then extend, creating a tubular structure called the cochlear duct. The cochlear duct then forms a spiral, completing two and one-half turns in the eighth week of gestation [6]. Over the subsequent four to five weeks, the organ of Corti (the sensory organ of the cochlea) develops. The perilymphatic scala vestibule and scala tympani develop above and below the organ of Corti and cochlear duct, completing the partitioning of the cochlea. Neural cells arising in the eighth cranial nerve invade the labyrinth. By the end of the second trimester, the inner ear is developed sufficiently to transduce vibratory energy into neural impulses that are transmitted to the brain [7].
GENETICS — The genes involved with ear development remain poorly understood. A number of genes have been found to be important for the development of the outer and middle ears, including HMX1, TCOF1, and EYA1. They often affect more than one part of the ear, and defects in these genes can result in complete loss of the outer and middle ear structures. Mutations in some of these genes (eg, TCOF1) are associated with human craniofacial syndromes (eg, Treacher Collins syndrome) (table 1) [8]. (See "Syndromes with craniofacial abnormalities".)
Several genes have been identified that control otic capsule formation, growth, and neural connection. HDAC1 has emerged as an important regulator of cell proliferation and cell survival. In animal models, the absence of HDAC1 can lead to failed inner ear development [9]. SOX2 has been shown to be critical for sensory development in the inner ear [10].
OUTER EAR MALFORMATIONS
Microtia — Incomplete development and growth of the pinna can lead to a small or deformed pinna (microtia) or absent pinna (anotia).
●Definition and epidemiology – In unilateral cases, microtia is defined as a size discrepancy between ears that exceeds normal variation (ie, >10 percent difference) [11]. The right side is affected more commonly than the left. Bilateral microtia is defined as a length of the external ear that is more than 2 standard deviations below the mean [12]. In severe cases, the pinna is completely absent (anotia). Microtia and anotia occur in 1 to 3 per 10,000 births [13].
●Association with genetic syndromes – Microtia and anotia may occur in isolation or in association with genetic syndromes and other malformations, including facial clefts, cardiac defects, limb anomalies, kidney anomalies, and holoprosencephaly [13-15]. Microtia is a common finding in children with Treacher Collins syndrome and craniofacial microsomia (also called Goldenhar syndrome, hemifacial microsomia, oculo-auriculo-vertebral spectrum, and first and second branchial arch syndrome). (See "Syndromes with craniofacial abnormalities", section on 'Treacher Collins syndrome' and "Syndromes with craniofacial abnormalities", section on 'Craniofacial microsomia'.)
Numerous other microtia-associated syndromes have been reported (table 1); these may be associated with single-gene defects or chromosomal abnormalities [15,16]. Genetic factors also appear to play an important role in isolated, nonsyndromic cases [17]. In a series of 145 cases, more than two-thirds were sporadic and approximately one-third were familial [14]. Among the familial cases, autosomal dominant inheritance was most common, but cases with autosomal recessive and multifactorial inheritance were also noted.
●Other risk factors – Microtia and anotia occur more frequently in boys; at increased altitude; with increasing birth order; in infants of diabetic mothers; and in infants with prenatal exposure to isotretinoin, thalidomide, alcohol, or mycophenolate [13,18-21].
●Classification – Several different classification systems for microtia have been proposed [16]. In the Marx system, type I microtia is characterized as a generally well-formed, perceptibly smaller auricle. In type II microtia, the pinna is malformed and 50 to 66 percent smaller than the contralateral pinna. In grade III microtia, the auricle is severely malformed and usually exhibits a peanut shape (picture 3) [22].
●Evaluation – Evaluation of infants with microtia and anotia includes audiologic testing and thorough examination to identify associated defects. In some cases, imaging may be warranted to detect associated abnormalities of the external auditory canal, middle, and inner ear [23].
Appropriate consultations in the neonatal period include a clinical geneticist, pediatric audiologist, pediatric otolaryngologist, or pediatric plastic surgeon. Although surgical correction of unilateral defects seldom is undertaken until the child reaches 6 to 10 years of age, these consultations are important to identify other abnormalities and provide reassurance for the families. Long-term management may include audiology, particularly if there is associated external auditory canal atresia (aural atresia). Amplification devices are beneficial for children with hearing loss [24]. (See "Hearing loss in children: Treatment".)
●Surgical repair – A minor abnormality of the pinna may not require correction. When the pinna is grossly deformed or absent, reconstruction is often warranted for cosmetic reasons. Traditional autologous cartilage repairs are undertaken when the child is 6 to 10 years of age, after the pinna has reached 80 percent of its adult size. Alloplastic repairs can be performed at a younger age [25].
Microtia repair with autologous cartilage is complex and often requires several stages [26]. A cartilage framework, usually derived from costal cartilage, is created and anchored beneath the skin of the mastoid area. Once it is well attached to surface skin, a postauricular crease is created in a second operation. Additional procedures often are employed for "fine-tuning." Even in the best hands, the complex structure of the external ear is difficult to duplicate and cosmetic results vary widely.
Reconstruction with synthetic auricular frameworks has gained in popularity, given the difficulty of creating an aesthetically pleasing auricle from autologous cartilage. This procedure is usually done in a single stage using a temporoparietal fascial flap to cover the artificial scaffold, which has reduced the rate of implant exposure and extrusion [27]. Research into customized three-dimensional scaffolds is ongoing [28]. The placement of a prosthetic auricle anchored with an osteointegrated peg remains an option [29].
Minor pinna malformations — Numerous descriptive and eponymous terms are used to classify auricular anomalies including cryptotia, prominent ear, lop ear, Stahl ear, crinkled ear, and many other subtle auricular variants (picture 4) [30].
Traditionally, these anomalies have been treated surgically during childhood by various operative techniques with variable results. However, many of these minor anomalies can be treated nonsurgically with molding during the newborn period (picture 4). When molding is performed immediately after birth, shorter periods of stenting are needed. It is hypothesized that hyaluronic acid is elevated by circulating estrogens in the first weeks after birth, accounting for the malleable nature of the newborn ear [31].
Protruding ears usually result from incomplete formation of the antihelical fold (picture 5). This abnormality has no functional significance. However, children with protruding ears sometimes are teased or bullied by their peers. For more severe cases, otoplasty can be performed later in childhood, typically when the child is four to six years old. The most common procedures involve the excision of skin from the posterior surface of the auricle and the placement of permanent sutures to reposition the ear and create an antihelical fold [32]. These techniques provide high rates of patient and family satisfaction [33]. Complications occur in 0 to 8 percent of otoplasties and include hematomas, perichondritis, suture extrusion, and keloid formation. Residual deformity and asymmetry of the two ears may occur [34].
Preauricular pits — Preauricular pits are small indentations located anterior to the helix and superior to the tragus of the ear (bilateral in 25 to 50 percent of cases) (picture 6). They are quite common, noted in approximately 1 percent of White children, 5 percent of Black children, and 10 percent of Asian children [35]. The prevalence is considerably higher in some family lineages [35]. Associated congenital anomalies occur in approximately one-third of the sporadic cases [36].
Infants with preauricular pits should have formal audiologic evaluation [37]. The risk of permanent hearing loss in children with preauricular pits or tags is five times that of the general population [37]. (See "Hearing loss in children: Screening and evaluation", section on 'Formal audiology'.)
The incidence of kidney anomalies in patients with isolated preauricular pits does not differ substantially from that of the general population [38,39]. (See 'Association with kidney anomalies' below.)
Preauricular pits may be the first indication of branchio-oto-renal (BOR) syndrome, one of the most common causes of hereditary hearing loss (picture 7). BOR is an autosomal dominant syndrome; most cases are due to mutations in the EYA1 and SIX1 genes [40]. It is characterized by sensorineural hearing loss (SNHL), preauricular pits, branchial cysts or tracts, malformed ears, and kidney anomalies including renal dysplasia and bifid renal pelvises [41]. (See "Renal hypodysplasia", section on 'Genetic disorders'.)
Preauricular pits do not require surgery unless they become repeatedly infected or discharge squamous material (picture 8) [35]. If surgery is performed, it should include excision of the pit, the squamous-lined cyst usually present beneath the skin (picture 9), and the cartilage at the root of the helix en bloc to avoid recurrence (picture 10) [42].
Accessory auricular appendage/preauricular tag — Accessory appendages composed of skin, subcutaneous fat, and/or cartilage may occur near the auricle or anywhere along the anterior border of the sternocleidomastoid muscle (picture 11). When they occur in the preauricular area, they are called preauricular tags.
Accessory auricular appendages and preauricular tags usually are removed in childhood for cosmetic purposes. Excision with plastic surgical closure provides better results than does neonatal ligation with suture or rubber bands because the lesions typically extend into subcutaneous tissue planes [43].
Children with accessory auricular appendages may have associated unilateral hearing loss and should undergo newborn hearing screening [37]. (See "Screening the newborn for hearing loss".)
Accessory auricular appendages, particularly at the tragus, with or without associated microtia may appear as part of the oculo-auriculo-vertebral spectrum (also called Goldenhar syndrome, hemifacial microsomia, facio-auriculo-vertebral spectrum, and first and second branchial arch syndrome). Preauricular tags may be seen in other genetic syndromes (eg, Townes-Brocks syndrome, BOR syndrome) [2,16]. (See "Syndromes with craniofacial abnormalities", section on 'Craniofacial microsomia'.)
Ear anomalies in CHARGE and DiGeorge syndromes — The external ear may have a characteristic appearance in these syndromes:
●CHARGE syndrome – In children with CHARGE syndrome (coloboma, heart defects, atresia choanae, retardation of growth and/or development, genital and/or urinary abnormalities, ear abnormalities and deafness), the ears are typically asymmetric between sides; have reduced vertical height; and have a cup-shaped, wide helix (picture 12) [44]. Aplasia and hypoplasia of the semicircular canals are common and often associated with balance and postural abnormalities [45].
●DiGeorge syndrome – Children with DiGeorge syndrome (also called 22q11.2 deletion syndrome or velocardiofacial syndrome) typically have a thick/overfolded helix and slightly low-set ears [46]. (See "DiGeorge (22q11.2 deletion) syndrome: Clinical features and diagnosis".)
Aural atresia (external auditory canal atresia) — Aural atresia is the absence of the external auditory canal, which can occur with or without microtia (picture 13).
●Embryology – Failure of complete invagination of the external auditory canal results in an absent or stenotic ear canal and improper formation of the eardrum. Failure of recanalization results in membranous stenosis or atresia. Formation of the malleus and incus occurs at the same time as invagination of the external auditory canal. Thus, children with aural atresia commonly have associated abnormalities of these ossicles, particularly fusion of the incus and malleus to each other or to atretic bone in the auditory canal.
●Management of hearing loss – Bilateral aural atresia is associated with a maximal conductive hearing loss (approximately 60 dB) and requires early intervention. Children with bilateral aural atresia should be fit with a bone-conduction hearing aid within weeks of birth to assist with early language acquisition [47]. (See "Hearing loss in children: Treatment", section on 'Bone conduction hearing devices'.)
The use of a bone-conduction/bone-anchored hearing aid in a child with unilateral aural atresia remains controversial. A bone-anchored aid may decrease head-shadow effect (ie, difficulty hearing sounds coming from the direction of the affected side) but does not normalize localization of sound [48]. Amplification is important if the child has hearing loss in the contralateral ear. The effect of unilateral hearing loss in aural atresia on learning remains controversial [49].
●Surgical correction – Surgery to correct aural atresia usually is performed toward the end of the first decade of life, when substantial mastoid development has occurred. Surgery entails the creation of a new ear canal and ear drum, providing a skin lining for the canal and drum, and mobilizing or repositioning the ossicles to allow transmission of sound. Surgery is more likely to be successful if extensive pneumatization of the mastoid air cells is present and the stapes is mobile. Hearing improvement after atresia repair is modest (approximately 25 dB) but may be sufficient to allow use of an ear-level hearing aid.
One of the major risks of this surgery is injury to the facial nerve or the dura of the middle cranial fossa. Thus, the procedure should be performed by an experienced otologist and with electrophysiologic facial nerve monitoring. Other complications include chronic myringitis, prosthesis displacement, SNHL, soft tissue stenosis, and tympanic membrane lateralization [50]. Revision surgery is required in approximately 25 percent of cases [50], and hearing results tend to degrade over time [51]. The new ear canal often requires cleaning and care for life [52].
The bone-anchored hearing aid is an alternative for patients who are not candidates for aural atresiaplasty, because of unfavorable anatomy or personal preference [53]. They provide superior and lasting hearing improvement compared with atresiaplasty. Devices that avoid a transcutaneous peg may improve patient acceptance of bone-anchored aids [54].
Children who have unilateral external auditory canal atresia may not benefit from atresia surgery if the contralateral ear has normal hearing [55]. Use of bone-anchored hearing aids in this setting is controversial [48].
●Risk of middle ear infections – Many children with external auditory canal atresia have normal middle ears and can develop acute otitis media (AOM). Children with aural atresia should be treated with antibiotics if AOM is suspected clinically because the diagnosis cannot be confirmed through otoscopy [24,56]. (See "Acute otitis media in children: Treatment", section on 'Initial antibiotic therapy'.)
Children with unrepaired aural atresia/stenosis also have a risk of developing cholesteatoma. Persistent ear pain or fever may be the only clues to this condition, which is diagnosed with computed tomography (image 1). (See "Cholesteatoma in children".)
MIDDLE EAR MALFORMATIONS — Congenital malformations of the ossicles may cause conductive hearing loss. Ossicular and other middle ear malformations occur as part of syndromes (eg, Treacher Collins, branchio-oto-renal (BOR), Stickler, velocardiofacial (DiGeorge), Beckwith-Wiedemann) and occasionally as isolated events. (See "Syndromes with craniofacial abnormalities" and "DiGeorge (22q11.2 deletion) syndrome: Clinical features and diagnosis" and "Beckwith-Wiedemann syndrome".)
The most common abnormalities of the ossicles are fixation of the malleus and/or incus, incudostapedial discontinuity, and stapes fixation. These defects in the middle ear's conducting mechanism cause hearing losses ranging from minor to maximal (60 dB) and have important effects on communication and learning. Each of these abnormalities is surgically correctable; correction of stapes fixation is most likely to fail because of the delicate attachment of the stapes to the inner ear [57].
INNER EAR MALFORMATIONS — The cochlea arises from a cystic invagination of surface epithelium (the otocyst) that pulls away from the vestibular portion of the inner ear during the first trimester and forms an elongating spiral. Failure of development along this pathway results in a wide variety of congenital malformations, many of which affect hearing.
The classic Michel and Mondini anomalies can be detected with high-resolution computed tomography or magnetic resonance imaging [58-61]:
●The Michel malformation occurs when the labyrinth is absent or reduced to a single cystic cavity.
●The Mondini malformation is present when cochlear growth is arrested at less than one complete turn (2.5 turns is normal) (picture 14). It is associated with complete deafness and vestibular malformations [62,63].
Several more complex classifications systems have been purposed and modified based upon hypoplasia or aplasia of cochleovestibular structures [64,65]. One system defines the following five general malformation categories based upon imaging findings [58]:
●Complete aplasia (Michel aplasia)
●Common cavity
●Cochlear aplasia with normally developed labyrinth
●Cochlear hypoplasia
●Incomplete partition (small cochlea with incomplete or missing interscalar septum; normal or malformed semicircular canals)
Another classification system expanded this to include >15 categories based upon high-definition computed tomography findings [65].
Minor abnormalities in the labyrinthine structure also can result in partial or progressive hearing loss. Enlarged vestibular aqueduct syndrome is the most common inner ear malformation. It may affect one or both ears (image 2) [66,67]. The hearing loss in children with large vestibular aqueduct syndrome may be sensorineural or mixed [68]. Some patients have normal hearing at birth, followed by progressive or fluctuating hearing loss. Sudden hearing loss may occur spontaneously or after minor head trauma. The degree of hearing loss is related to the extent of dilation of the vestibular aqueduct [69].
Children with genetic sensorineural hearing loss (SNHL) have a high incidence of minor malformations of the semicircular canals, cochlea, and internal auditory canal [70]. Hypoplasia of the semicircular canals is common in patients with CHARGE syndrome [71]. Pendred syndrome is one of the most common syndromic causes of SNHL. It is characterized by severe to profound bilateral SNHL that is usually congenital (or prelingual) and nonprogressive, vestibular dysfunction, temporal bone abnormalities, and development of euthyroid goiter in late childhood to early adulthood. (See "Hearing loss in children: Etiology", section on 'Hereditary'.)
Autosomal recessive deafness with enlarged vestibular aqueduct (DFNB4) is caused by mutations in SLC26A4 and, less commonly, double heterozygous mutations of FOXI1/SLC26A4 and KCNJ10/SLC26A4. DFNB4 is characterized by nonsyndromic sensorineural hearing impairment, vestibular dysfunction, and enlarged vestibular aqueduct. Thyroid defects are not seen in DFNB4 [72].
ASSOCIATION WITH KIDNEY ANOMALIES — We suggest that a kidney ultrasound be obtained in children with an ear anomaly accompanied by any of the following:
●Other malformations or dysmorphic features
●Family history of deafness or auricular or kidney malformations
●Maternal history of gestational diabetes
In addition, some experts suggest that kidney ultrasound be performed in children with isolated preauricular pit or cup ear [73]. However, this recommendation is controversial.
Children with external ear anomalies, particularly preauricular pits and cup ears, have a slightly increased risk of kidney anomalies [74-76]; however, the incidence of kidney anomalies in patients with isolated preauricular pits (ie, without other malformations or dysmorphic features) appears to be similar to that of the general population [38,39]. External ear malformations and kidney anomalies occur in several multiple congenital anomaly (MCA) syndromes, including:
●Branchio-oto-renal (BOR) syndrome
●CHARGE syndrome
●Diabetic embryopathy (see "Infants of women with diabetes")
In a prospective study, 108 out of 17,286 infants born at a single medical center during a four-year period had isolated preauricular tags or pits [38]. The infants were examined by a geneticist to confirm the absence of other congenital anomalies and underwent kidney ultrasound at one to three months of age. Their ultrasonography findings were compared with those of 95 healthy infants who underwent ultrasonography on the second day of life. The prevalence of kidney abnormalities was similar between groups (2.2 and n3.1 percent in cases and controls, respectively). The abnormalities included mild pyelectasis (in two cases and three controls) and renal calculus (in one control). The authors concluded that kidney ultrasound is not indicated in infants with isolated preauricular pits or tags.
In a retrospective report of 42 children with ear anomalies (including preauricular pits or tags, microtia, anotia, cup, lop, or other dysplastic ear) who were referred for genetics evaluation at one of two tertiary medical centers, 33 (79 percent) were diagnosed with an MCA syndrome and the remaining nine had isolated ear anomalies (most commonly preauricular pits) [73]. One-third of children with MCA syndromes had abnormalities on kidney ultrasound compared with only one of the nine children with isolated ear anomalies.
SUMMARY AND RECOMMENDATIONS
●Outer ear anomalies – Congenital outer ear anomalies include (see 'Outer ear malformations' above):
•Microtia(picture 3)
•Minor pinna malformations (eg, helix, crinkled ear, Stahl ear (picture 4),and protruding [lop] ear (picture 5))
•Preauricular pits (picture 6)
•Accessory auricular appendages/preauricular tags (picture 11)
•Aural/external auditory canal atresia (picture 13)
●Middle ear anomalies – Congenital middle ear anomalies include malformations of the ossicles (eg, fixation or incudostapedial discontinuity) and may result in conductive hearing loss. Ossicular malformations may occur as part of a syndrome or in isolation. (See 'Middle ear malformations' above.)
●Inner ear anomalies – Congenital inner ear anomalies include the Michel and Mondini malformations and the enlarged vestibular aqueduct syndrome. (See 'Inner ear malformations' above.)
●Association with kidney anomalies – External ear malformations and kidney anomalies occur in several multiple congenital anomaly (MCA) syndromes. We suggest that kidney ultrasound be performed in children with ear anomalies and any of the following:
•Other malformations or dysmorphic features
•Family history of deafness or auricular or kidney malformations
•Maternal history of gestational diabetes
The incidence of kidney anomalies in patients with isolated preauricular pits (ie, without other malformations or dysmorphic features) appears to be similar to that of the general population. (See 'Association with kidney anomalies' above.)
