More than 24,000 children are born with hearing loss in the United States each year. Boys Town National Research Hospital is a national leader in the diagnosis and treatment of children with moderate to profound hearing loss.

Information on Hearing Loss - Ten Syndromes Most Commonly Associated With Hearing Impairment

Syndromic hearing loss - that is, hearing loss in association with other congenital or genetic abnormalities, is a frequent occurrence. In fact, in a search under the London Dysmorphology Database (Oxford Medical Publishers) one finds at least 396 multiple anomaly syndromes in which hearing loss is listed as a significant feature of the condition. Thus, it is not as easy as one might think to define the "ten most common" syndromes with hereditary hearing loss.

One major problem is simply how does one define "common"? Potentially, the most frequent hearing loss syndromes would be in those conditions which themselves are common, and hearing loss a variably occurring component of the syndrome. Such examples might include cleft lip and cleft palate (where most of the hearing loss is secondary), Noonan syndrome, or the hereditary peripheral motor and sensory neuropathies (Charcot-Marie-Tooth disorders). I have chosen to take the opposite approach, which is to look at all of our patients who carry the diagnosis of hearing loss, and who also have another associated clinical congenital anomaly or genetic feature, and look at the most common recurring diagnoses.

One major problem is simply how does one define "common"? Potentially, the most frequent hearing loss syndromes would be in those conditions which themselves are common, and hearing loss a variably occurring component of the syndrome. Such examples might include cleft lip and cleft palate (where most of the hearing loss is secondary), Noonan syndrome, or the hereditary peripheral motor and sensory neuropathies (Charcot-Marie-Tooth disorders). I have chosen to take the opposite approach, which is to look at all of our patients who carry the diagnosis of hearing loss, and who also have another associated clinical congenital anomaly or genetic feature, and look at the most common recurring diagnoses.

Thus, my list of the 10 most common syndromes with that have hearing loss would include:

1. Hemifacial microsomia
2. Stickler syndrome
3. Congenital cytomegalo virus
4. Usher syndrome
5. Branchio-oto-renal syndrome
6. Pendred syndrome
7. CHARGE Association
8. Neurofibromatosis type II
9. Mitochondrial disorders
10. Waardenburg syndrome

Before describing these conditions in more detail, it is probably worth mentioning that there is a group of syndromes that in themselves are rare disorders, but in which hearing loss is a consistent/major feature and thus represent a significant group of conditions when one discusses hereditary hearing loss. A list of such conditions would include the oto-palatal-digital syndromes, the oral-facial-digital syndromes, skeletal dysplasias (in particular, osteogenesis imperfecta), metabolic storage disorders (especially mucopolysaccharidoses and Refsum's disease), Townes-Brock syndrome, and Wildervanck syndrome.

(1) Oculo-Auriculo-Vertebrali (OAV) Spectrum (Hemifacial Microsomia, Goldenhar syndrome)

Incidence and Prevalence: Unknown
Features: The major features include facial asymmetry of varying degrees, ocular findings (including anophthalmia and microphthalmia, and epibulbar dermoids), auricular abnormalities (a spectrum from mild morphologic changes of the pinnae to complete anotia), and vertebral changes such as cervical spine and cranial base malformations.
Hearing Loss: 50% of patients with OAV have a conductive and/or sensorineural hearing loss. The etiology of the hearing loss is extremely varied; this includes anomalies of the middle and external ears, auricular abnormalities, cranial nerve abnormalities, eustachian tube malformations and dysfunction, and abnormalities of the skull cranial base.
Comments: Due to the extraordinarily wide range of possible contributing factors to the hearing loss, a detailed evaluation of the entire auditory aparatus should be performed in every patient with the diagnosis of OAV.

(2) Stickler Syndrome (Marshall-Stickler Syndrome, Hereditary Arthro-ophthalmopathy)

Incidence and Prevalence: Unknown (See Comments.)
Features: The major clinical stigmata of Stickler syndrome include flattening of the facial profile, cleft of the palate, ocular changes (myopia/retinal detachment/cataracts), and arthropathy.
Hearing Loss: Many patients with Stickler syndrome have hearing loss due to eustacian tube dysfunction secondary to palatal anomalies. A smaller group will have high frequency sensorineural hearing loss, which may be progressive. Conductive abnormalities have also been noted.
Comments: The overall incidence and prevalence of Stickler syndrome is unknown. It has been suggested that there is a higher frequency of this condition in the midwest region of the United States. Our clinical experience would strongly support this presumption.

(3) Congenital Cytomegalo Virus (CMV)

Incidence and Prevalence: Congenital CMV as a condition is reported to occur 1 in 3500 live births. How common CMV as an etiologic agent for isolated congenital hearing loss is unknown.
Features: Consistent features include hepatosplenomegaly, thrombocytopenia, jaundice, and hemolytic anemia. Other features include microcephaly, intrauterine growth retardation, cerebral calcifications, and central nervous system disruptions. Hearing Loss: Hearing loss is sensorineural and may be progressive.
Comments: Extreme caution should be made in attributing the etiology of an isolated sensorineural hearing loss to CMV. Single random titres beyond the neonatal period that are in the "positive" range in a patient with sensorineural hearing loss is by no means a diagnostic confirmation of etiology. Strict adherence to serologic and epidemiologic criteria for the diagnosis of congenital CMV as a cause of hearing loss must be adhered to.

(4) Usher Syndrome

Incidence and Prevalence: Usher syndrome is the most common eye/ear disorder with a reported prevalence of 3.5 per 100,000. It is estimated that about 10% of all children with sensorineural hearing loss have Usher syndrome. Conversely, 10% of patients with retinitis pigmentosa will have a significant hearing loss.
Features: Retinitis pigmentosa, sensorineural hearing loss.
Hearing Loss: Type I, congenital, severe to profound, absent vestibular functions; Type II, congenital, moderate to severe; Type III, progressive.
Comments: Not every patient who has the combination of retinitis pigmentosa and sensorineural hearing loss has Usher syndrome. Detailed evaluation including ERGs, vestibular responses, and exclusion of other syndromes associated with retinitis pigmentosa and hearing loss must be performed. Patients with Usher I may be delayed in the acquisition of early motor milestones.

(5) Branchio-Oto-Renal Syndrome (BOR)

Incidence and Prevalence: Prevalence 1 per 40,000. It is estimated that 2% of all children with profound hearing loss may have branchio-oto-renal syndrome.
Features: Branchial abnormalities including branchial clefts, fistulas, and cysts. Otologic changes include malformation of pinnae and preauricular pits of the sinuses. The renal anomalies are markedly varied, and oftentimes asymptomatic.
Hearing Loss: 75% of patients with BOR will have a significant hearing loss. A breakdown of the type of hearing loss seen would be: conductive (30%), sensorineural (20%), and mixed (50%).
Comments: Detailed imaging studies may be required to identify specific renal malformations.

(6) Pendred Syndrome

Incidence and Prevalence: It is estimated that 5% of all children with congenital hearing loss may have Pendred syndrome.
Features: The cardinal features of Pendred syndrome are a thyroid goiter and profound congenital sensorineural hearing loss. The goiters are reported to be half-hypothyroid, half-euthyroid. The underlying defect appears to be an abnormality in iodine trapping (organification).
Hearing Loss: Present in most patients with Pendred syndrome. Severe in over 50% of the time. On rare occasions, the hearing loss is reported to be only minimal. The hearing loss may also be progressive in childhood with a reported incidence of progression in 15% to 20%.
Comments: Surveys of school-age children in schools for the deaf have shown that as many as 50% of these children will show an abnormal perchlorate washout. This suggests the condition is much more common than initially suspected and probably under-diagnosed. Any child with congenital hearing loss should have an evaluation which includes a perchlorate washout - this currently is not included in a standard evaluation. Simple serum testing for thyroid status will often miss subtle abnormalities of thyroid function. Patients frequently have Mondini malformations; head trauma may precipitate a sudden hearing loss within this group.

(7) CHARGE Association

Incidence and Prevalence: Unknown.
Features: Reported major features account for the acronym CHARGE with C for coloboma, H for heart, A for atresia choanae, R for retarded growth and development, G for genital hypoplasia, and E for ear anomaly/deafness.
Hearing Loss: Universally reported as mixed and occurs in 80% to 85% of patients with CHARGE Association.
Comments: None.

(8) Neurofibromatosis Type II

Incidence and Prevalence: Birth incidence is reported to be 1 in 40,000; prevalence in adulthood is reported to be anywhere from 1 in 200,000 to 1 in one million.
Features: Vestibular schwannomas with secondary hearing loss, and other intracranial tumors.
Hearing: Hearing loss is present in 45% of patients. The loss is unilateral in 75% of patients and is progressive.
Comments: Any adult presenting with noncongenital unilateral hearing loss has neurofibromatosis II until proven otherwise. Cranial imaging (magnetic resonance imaging [MRI]) is indicated as the key diagnostic tool for these patients.

(9) Mitochondrial Disorders

Incidence and Prevalence: Unknown.
Features: Abnormalities of mitochondrial DNA can produce either an isolated hearing loss, or a hearing loss associated with other features associated with mitochondrial disease. This would include lactic acidosis, encephalopathy, myopathy, seizure disorder,ophthalmoplegia, diabetes mellitus, cardiomyopathy/cardiac conduction defects, stroke-like episodes, ataxia, and optic atrophy.
Hearing Loss: Sensorineural.
Comments: Any hearing loss demonstrating a maternal inheritance pattern should clearly be considered for mitochondrial etiology. Diagnostic workup is difficult, but detailed in many good reviews on the subject.

(10) Waardenburg Syndrome

Incidence and Prevalence: 1 per 4,000 live births. In some surveys, 2.3% of all children with congenital hearing loss have Waardenburg syndrome.
Features: There are at least two types of Waardenburg syndrome. The major distinguishing feature between type I and type II is the presence or absence of dystopia canthorum. The craniofacial findings include hypertelorism, synophrys, high nasal bridge, and hypoplastic alae nasi. There are also multiple pigmentary abnormalities which include hypopigmentation of the fundi, a white forelock, partial albinism, early greying, and blue irides.
Hearing Loss: Type I: 20%; Type II: 50%. Hearing loss may be unilateral or bilateral; in all cases it is sensorineural.
Comments: None.

G. Bradley Schaefer, M.D. is an Associate Professor of Pediatrics and Chief of Clinical Genetics at the Meyer Rehabilitation Institute University of Nebraska Medical Center. He is also the clinical genetics consultant to the NIDCD Hereditary Hearing Impairment Resource Registry.

Date Originally Created: Fall 0f 1995

The information presented here first appeared in publications of the Boys Town National Research Register for Hereditary Hearing Loss, the National Institute on Deafness and Other Communication Disorders (NIDCD), Hereditary Hearing Impairment Resource Registry (HHIRR), or the Boys Town Research Registry for Hereditary Hearing Loss.

The Boys Town Research Registry for Hereditary Hearing Loss

The Boys Town Research Registry for Hereditary Hearing Loss (Registry) is designed to foster a partnership between families, clinicians and researchers in the area of hereditary hearing loss/deafness through three primary functions. First, the Registry disseminates information to professionals and families about clinical and research issues related to hereditary deafness/hearing loss. Second, the Registry collects information from individuals interested in supporting and participating in research projects. This information is used to support the third function of the Registry - matching families with collaborating research projects.

For more information, contact us at:

Research Registry for Hereditary Hearing Loss
555 N. 30th Street Omaha, NE 68131
800 320-1171 (V/TDD)
402 498-6331 (FAX)