Syndromic Sensorineural Hearing Loss 

Sensorineural hearing loss (SNHL) is a common disorder that affects millions of people. Hearing loss has many different presentations, ranging in severity from mild to profound, including low- and high-pitch patterns, and can affect people of any age.

Genetic hearing loss may be present at birth (congenital) or may progress in either childhood or adulthood. About 50% of congenital hearing loss is genetic and about 50% is acquired. Genetic hearing loss may appear as an isolated finding or as part of a syndrome. About 70% of genetic hearing loss is nonsyndromic and about 30% is syndromic. The London Dysmorphology Database lists 396 syndromes that include hearing loss among the anomalies.^[1] The most common and unique syndromes are discussed in this article. The reader is directed to the eMedicine topic Genetic Sensorineural Hearing Loss for a general discussion of genetic hearing loss.

The auditory system is highly complex, and disruptions at the level of the middle ear, cochlea, and central nervous system can result in variable degrees of hearing loss. Hearing also depends on precise biochemical, metabolic, vascular, hematologic, and endocrine function. Disruption in any of these systems can profoundly affect the auditory system. The pathophysiology differs with each type of syndromic hearing loss. This article attempts to describe the basic pathophysiology of each syndrome, as it is currently understood. However, the molecular structure and pathways of the hearing system is largely undiscovered. It is interesting to note that the study of the genetic basis of hearing loss continues to enhance the understanding of the molecular basis of normal hearing.^[2]

Frequency

United States

About 21 million persons are hearing impaired, and approximately 1% of those persons are profoundly hearing impaired. Approximately 4000 hearing-impaired infants are born each year. The average incidence of hearing loss in neonates in the United States is 1.1 per 1000, with variability among states ranging between 0.22 and 3.61, according to Mehra et al.^[3] In this study, the prevalence of childhood and adolescent hearing loss was 3.1%, with higher rates in Hispanic Americans and in families with lower incomes.^[3]

Filtering out the prevalence of syndromic hearing loss among nonsyndromic and nonhereditary hearing loss is a difficult and imperfect task, given phenotypic variability, complicating medical risk factors, and incomplete family histories. After reviewing 780 abstracts and summarizing 43 studies published in English between 1966 and 2002, Morzaria et al reported that the most common etiologies of hearing loss in children were unknown (37.7%) and genetic nonsyndromic (29.2%), while genetic syndromic hearing loss accounted for 3.2% of the etiologies.^[4]

International

Hearing impairment affects up to 30% of the international community, and estimates indicate that 70 million persons are deaf. Proportions of hereditary verses acquired and syndromic versus nonsyndromic hearing losses across populations is highly variable and is heavily influenced by multiple factors, some likely not yet identified, including drift of populations, frequency of consanguinity, and health status. Estimating the prevalence of hereditary hearing loss in populations across the world is very difficult, since access to health care, poor health conditions, and a low level of awareness of hearing loss is compounded by a higher frequency of complicating risk factors such as neonatal distress, prematurity, high fever, otitis media, meningitis, ototoxic medications, and illnesses such as rubella.^[5]

Ancestry and race play a large role in the prevalence of syndromic hearing loss and may influence the prevalence of nonsyndromic and acquired hearing losses. Saunders et al studied a rural community in Nicaragua and demonstrated a prevalence of significant hearing loss of 18% in a group of school-aged children in which 24% of the children had an identifiable family history of hearing loss. In a clinic-based group of 96 patients with hearing loss, dysmorphic features were recognized in many of the children, including atresia, low-set or cup ear deformity, juvenile cataracts, malar hypoplasia, hemifacial microsomia, micrognathia, and branchial cleft cysts. Five children had features that suggested a defined syndrome (neurofibromatosis, Goldenhar, branchio-oto-renal syndrome, Poland syndrome, and Down syndrome), but many others had significant dysmorphisms that were thought to be either unrelated to hearing loss or could not be diagnosed as a defined syndrome.^[5]

Additionally and ideally, large-scale epidemiologic studies are needed and will become more informative as molecular testing is made available to the world’s populations.

Mortality/Morbidity

The morbidity of hearing loss varies with the severity of involvement; however, it is a significant problem even for the most mildly involved. Patients with unilateral hearing loss have difficulty hearing in background sound and difficulty localizing sound. Bilateral profound hearing loss has a great potential for morbidity. Many studies support that deafness significantly affects quality of life. Social, educational, and earning potential are diminished.

In patients with syndromic hearing loss, morbidity and mortality is often more significant with anomalies of the other involved system or systems. For example, children with Jervell and Lange-Nielsen syndromes are at risk for syncope, arrhythmias, and sudden death. Children with Usher syndrome develop hearing loss, vestibular impairment, and visual impairment. Usher syndrome accounts for a large percentage of the etiology of deaf-blindness. The dual sensory impairment has huge implications for communication and education. Glomerulonephrosis associated with Alport syndrome can end in kidney failure and necessitate kidney transplant.

Age

Early identification of hearing loss and appropriate intervention provides the best opportunity for counseling, habilitation, and development. Additionally, early enrollment in services for a child with hearing impairment reduce health care, special education, and other service costs for families and taxpayers. Prior to the initiation of universal hearing screening for newborns, fewer than 50% of children who are hearing impaired were identified before age 3 years. Identification of risk factors (prematurity, low birth weight, low Apgar scores) detects less than 50% of infants who have or are at risk for hearing loss.

Currently, 36 states mandate hearing screening for newborns according to the National Newborn Screening and Genetic Resource Center, as of 3/11/2009. Screening is almost universally offered in the remaining states but not required by law. Currently, the average age at detection is about 14 months. However, in Virginia, where universal infant screening has been mandated by law since July 1, 2000, and became greater than 98% compliant by 2004, the average age at diagnosis decreased from 16.2 months to 4.5 months.

Children with syndromic features associated with hearing loss should be screened early and routinely for hearing loss. Even if initial screening examinations indicate normal hearing, they remain at risk. During infancy and early childhood, parents should be aware of and questioned about the child's achievement of hearing and language milestones. Parental concerns should be taken seriously. If risks for hearing loss are high or the child does not seem to be meeting landmarks, a hearing evaluation should be performed. Some syndromes, such as Pendred, Alport, Refsum, neurofibromatosis type II, Usher, and osteopetrosis, may place the patient at risk for progressive hearing loss