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Waardenburg syndrome

Waardenburg syndrome is a genetic disorder associated with hearing loss and changes in skin and hair pigmentation. The syndrome is named for Dutch ophthalmologist Petrus Johannes Waardenburg who first described it. more...

Waardenburg syndrome
Wagner's disease
WAGR syndrome
Wallerian degeneration
Warkany syndrome
Watermelon stomach
Wegener's granulomatosis
Weissenbacher Zweymuller...
Werdnig-Hoffmann disease
Werner's syndrome
Whipple disease
Whooping cough
Willebrand disease
Willebrand disease, acquired
Williams syndrome
Wilms tumor-aniridia...
Wilms' tumor
Wilson's disease
Wiskott-Aldrich syndrome
Wolf-Hirschhorn syndrome
Wolfram syndrome
Wolman disease
Wooly hair syndrome
Worster-Drought syndrome
Writer's cramp

Pigmentation changes may include irises of varying color (heterochromia), or a patch of white or grey hair. Hearing loss may be absent, moderate, or profound.

Types of Waardenburg syndrome

There are several subtypes of the syndrome, traceable to different genetic variations. Dystopia canthorum, a widened bridge of the nose because of lateral displacement of the inner canthus of each eye, is associated with type I.

  • Type I: associated with mutations in the paired box 3 (PAX3) gene.
  • Type IIa: associated with mutations in the microphthalmia-associated transcription factor (MITF) gene
  • Type IIb: associated with a locus designated WS2B
  • Type IIc: associated with a locus designated WS2C
  • Type IId: associated with a deletion in the SNAI2 gene. Very rare.
  • Type III: associated with mutations in the paired box gene 3 (PAX3) gene
  • Type IV: Waardenberg-Hirschsprung disease, or Waardenburg-Shah syndrome, is associated with mutations in the endothelin-B receptor gene (EDNRB), the gene for its ligand, endothelin-3 (EDN3), or in the SRY-related HMG-box gene 10 (SOX10) gene. This subtype may include neurologic manifestations.


This condition is usually inherited in an autosomal dominant pattern, which means one copy of the altered gene is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition. A small percentage of cases result from new mutations in the gene; these cases occur in people with no history of the disorder in their family.

Some cases of type II and type IV Waardenburg syndrome appear to have an autosomal recessive pattern of inheritance, which means two copies of the gene must be altered for a person to be affected by the disorder. Most often, the parents of a child with an autosomal recessive disorder are not affected but are carriers of one copy of the altered gene.


This article incorporates public domain text from The U.S. National Library of Medicine


  • Waardenburg syndrome at OMIM, Genetic disorder catalog


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Newborn Hearing Screening: Recommendations and Rationale — U.S. PREVENTIVE SERVICES TASK FORCE
From American Family Physician, 12/15/01

This statement summarizes the third U.S. Preventive Services Task Force (USPSTF) recommendations on newborn hearing screening and the supporting scientific evidence, and it updates the 1995 recommendations contained in the Guide to Clinical Preventive Services, second edition.(1) Explanations of the ratings and the strength of overall evidence are provided in Tables 1 and 2, respectively. This is an abridged version of the original Recommendations and Rationale Statement, which is available on the USPSTF Web site ( The complete information on which this statement is based, including evidence tables and references, is available in the article, "Universal Newborn Hearing Screening: A Summary of the Evidence"(2) and in the Systematic Evidence Review(3) and Summary of the Evidence on this topic, which also can be obtained through the USPSTF Web site (, through the National Guideline Clearinghouse (, or in print through the Agency for Healthcare Research and Quality Publications Clearinghouse (800-358-9295).


USPSTF Recommendations and Ratings

The USPSTF grades its recommendations according to one of five classifications (A, B, C, D, I) reflecting the strength of evidence and magnitude of net benefit (benefits minus harms):

A. The USPSTF strongly recommends that clinicians routinely provide [the service] to eligible patients. The USPSTF found good evidence that [the service] improves important health outcomes and concludes that benefits substantially outweigh harms.

B. The USPSTF recommends that clinicians routinely provide [the service] to eligible patients. The USPSTF found at least fair evidence that [the service] improves important health outcomes and concludes that benefits outweigh harms.

C. The USPSTF makes no recommendation for or against routine provision of [the service]. The USPSTF found at least fair evidence that [the service] can improve health outcomes but concludes that the balance of benefits and harms is too close to justify a general recommendation.

D. The USPSTF recommends against routinely providing [the service] to asymptomatic patients. The USPSTF found at least fair evidence that [the service] is ineffective or that harms outweigh benefits.

I. The USPSTF concludes that the evidence is insufficient to recommend for or against routinely providing [the service]. Evidence that [the service] is effective is lacking, of poor quality or conflicting, and the balance of benefits and harms cannot be determined.

USPSTF = U.S. Preventive Services Task Force.


USPSTF Strength of Overall Evidence

The USPSTF grades the quality of the overall evidence for a service on a three-point scale (good, fair, poor): Good: Evidence includes consistent results from well-designed, well-conducted studies in representative populations that directly assess effects on health outcomes.

Fair: Evidence is sufficient to determine effects on health outcomes, but the strength of the evidence is limited by the number, quality or consistency of the individual studies, generalizability to routine practice, or indirect nature of the evidence on health outcomes.

Poor: Evidence is insufficient to assess the effects on health outcomes because of limited number or power of studies, important flaws in their design or conduct, gaps in the chain of evidence, or lack of information on important health outcomes.

USPSTF = U.S. Preventive Services Task Force.

Summary of Recommendation

* The USPSTF concludes that the evidence is insufficient to recommend for or against routine screening of newborns for hearing loss during the postpartum hospitalization (I recommendation).

The USPSTF found good evidence that newborn hearing screening leads to earlier identification and treatment of infants with hearing loss. However, evidence to determine whether earlier treatment resulting from screening leads to clinically important improvement in speech and language skills at age three years or older is inconclusive because of design limitations in existing studies.

Although earlier identification and intervention may improve the quality of life for the infant and family during the first year of life, and prevent regret by the family because of delayed diagnosis of hearing loss, the USPSTF found few data addressing these benefits. The USPSTF could not determine from existing studies whether these potential benefits outweigh the potential harms of false-positive tests that many low-risk infants would experience following universal screening in high- and low-risk groups.

The USPSTF found good evidence that the prevalence of hearing loss in infants in the newborn intensive care unit (NICU) and those with other specific risk factors (see "Clinical Considerations") is 10 to 20 times higher than the prevalence of hearing loss in the general population of newborns. Both the yield of screening and the proportion of true positive results will be substantially higher when screening is targeted at these high-risk infants, but selective screening programs typically do not identify all infants with risk factors. Evidence that early identification of and intervention for hearing loss improves speech, language or auditory outcomes in high-risk populations is also limited.

Clinical Considerations

* Currently, universal newborn hearing screening is required by law in more than 30 states and is performed routinely in some health care systems in other states. Selective screening of infants in the NICU and those with other risk factors for hearing loss is conducted in many settings that do not follow a policy of universal screening. Clinicians should be aware of such screening policies in their practice environments.

* Risk factors for sensorineural hearing loss (SNHL) among newborns include NICU admission for two days or more; syndromes known to include hearing loss (e.g., Usher's syndrome, Waardenburg's syndrome); family history of childhood SNHL; congenital infections (e.g., toxoplasmosis, bacterial meningitis, syphilis, rubella, cytomegalovirus, herpes virus); and craniofacial abnormalities (especially morphologic abnormalities of the pinna and ear canal).

* If a program for routine hearing screening of newborns is implemented, it should include systematic education to fully inform parents and clinicians about the potential benefits and harms of the testing protocol. Most infants with positive in-hospital screening tests will subsequently be found to have normal hearing, and clinicians should be prepared to provide reassurance and support to parents of infants who need follow-up audiologic evaluation.

* If any program for newborn hearing screening is implemented, screening should be conducted using a validated protocol, usually requiring two screening tests. Equipment used should be well maintained, staff should be thoroughly trained, and quality control programs to reduce avoidable false-positive tests should be in place. Programs should develop protocols to ensure that infants with positive screening tests receive appropriate audiologic evaluation and follow-up after discharge.

Scientific Evidence


Each year, an estimated 5,000 infants are born in the United States with moderate, severe, or profound bilateral SNHL. The estimated prevalence of bilateral SNHL is one to two per 1,000 newborns in the United States, but may be 10 to 20 times higher among infants in the NICU than in the healthy nursery population. Prevalence of bilateral SNHL is also increased in infants with other selected risk factors (see "Clinical Considerations").

The diagnosis of congenital hearing loss is often delayed. In one survey conducted before hearing screening was common, the median age at diagnosis was 13 months for infants with severe to profound bilateral SNHL and 17 months for those with mild to moderate hearing loss.(4)

Children with hearing loss experience delayed development in language, learning, and speech. Impairment exists as early as age three years and has consequences throughout life, leading to lower reading abilities, poorer school performance, and under- or unemployment.


Between 50 and 75 percent of infants with moderate to profound bilateral SNHL have one or more specific risk factors (see "Clinical Considerations").(5,6) Until recently, most newborn hearing screening programs in the United States focused on identifying and screening infants at risk for SNHL. However, these programs typically do not identify infants at risk for hearing loss because of failure to administer screening questionnaires or loss to follow-up, and they will miss affected infants who have no risk factors.

In the late 1990s, the development of rapid, low-cost screening tests made it feasible to implement screening programs for all newborns for congenital hearing loss during the birth hospitalization. Two types of tests are commonly used: otoacoustic emissions (OAEs) and auditory brainstem response (ABR). Typically, screening programs use a two-stage screening approach (OAE repeated twice, OAE followed by ABR, or automated ABR repeated twice). Criteria for defining a "pass" or "fail" on the initial screening test vary, and results are sensitive to equipment, the tester's level of training, and ongoing quality control.

The true sensitivity and specificity of newborn hearing screening are difficult to estimate from most screening programs. One large, good-quality study measured the sensitivity and specificity of OAE and ABR using an independent "gold standard," visual reinforcement audiometry, performed at age eight to 12 months.(7) One-stage screening with an ABR or OAE test can detect 80 to 95 percent of affected ears, depending on how an abnormal test result is defined. The two-stage protocol of OAE and ABR missed 11 percent of affected ears, but was more specific than testing with the ABR or OAE alone. Because the prevalence of SNHL is low, there are many more false positives than true positives, especially in low-risk populations. Overall, 6.7 percent of infants who failed in-hospital screening tests were eventually diagnosed with bilateral SNHL in the best study of newborn hearing screening; among those without risk factors for hearing loss, only 2 percent of those who failed such screening tests were later found to have SNHL.(8)

Children who fail in-hospital screening tests are usually referred for repeat testing two to eight weeks after discharge; positive second-stage results are usually validated by a combination of otolaryngologic and audiologic consultation, diagnostic ABR testing, or other electrophysiologic testing that can be performed as early as age three months. Visual reinforcement audiometry cannot be performed reliably before age eight to nine months.

Universal newborn hearing screening reduces the age at which infants with hearing loss are diagnosed and treated. Studies of statewide universal newborn hearing screening programs in the United States have found that the mean age at which hearing impairment is identified has decreased from 12 to 13 months before screening programs were introduced to three to six months since their introduction.(9,10) The mean age at which infants receive hearing aids has been reduced from 13 to 16 months before universal screening programs began to five to seven months(9,11) following their introduction. In a large, controlled study comparing in-hospital universal newborn hearing screening with no screening, universal screening significantly increased the number of infants with hearing loss referred to audiologists by the age of six months and increased the probability that infants with moderate to severe hearing loss would be diagnosed by the age of 10 months (57 versus 14 percent).(8) Compared with selective screening of high-risk newborns, universal screening would result in the early diagnosis (younger than 10 months of age) of one additional case for every 1,441 infants screened, and early treatment (younger than 10 months of age) of one additional case for every 2,401 newborns screened, according to one estimate.(2,3)


There are no prospective, controlled studies that directly examine whether newborn hearing screening and earlier intervention result in improved speech, language, or educational development.

Although several retrospective studies have concluded that infants entering treatment programs at younger ages, or infants identified in hospitals with universal screening programs, have better long-term language outcomes,(2,3) these studies have significant methodologic flaws.

All of the available retrospective studies began with a convenience sample of children enrolled in early intervention programs, rather than with an inception cohort of children at the point of hearing loss identification. None of the studies described loss to follow-up between enrollment in the intervention program and the age of assessment, and criteria for inclusion and exclusion were not clearly described. In most studies, early identification was not necessarily the result of screening. Therefore, underlying differences between children identified or enrolled early and those identified or enrolled late may have contributed to the observed language differences. Although some studies attempted to adjust for appropriate confounding factors, the USPSTF judged that statistical adjustment cannot compensate for the potential biases arising from unbalanced cohort selection, concluding that the studies do not establish the effectiveness of early identification and treatment.


Because universal newborn hearing screening reduces the average age for intervention by six to nine months, improved hearing and increased prelanguage stimulation over that period might be considered important benefits of newborn hearing screening. In addition, hearing-impaired children and their parents might benefit psychologically by avoiding regret in the future caused by a delayed diagnosis and treatment of hearing impairment. However, the USPSTF was unable to identify any evidence that would allow it to assess the magnitude of these potential benefits or determine whether they alone were sufficient to offset the potential harms of screening.

Because most positive screening tests are false positives, the most likely potential adverse effects of screening are parental anxiety and misunderstanding, and labeling of normal infants as hearing-impaired until the definitive diagnosis can be made months later. Even a slightly increased risk of these effects could have a large impact on the net benefit of a screening program. In low-risk populations, 25 to 50 false positives occur for each true case of hearing impairment.(8) In existing newborn hearing screening programs, 13 to 31 percent do not follow up for definitive testing, which might allay concerns about the health of the infant.

Recommendations of Others

The Joint Committee on Infant Hearing 2000 Position Statement, developed and approved by the American Academy of Audiology, the American Academy of Pediatrics, the American Speech-Language-Hearing Association, the Council on Education of the Deaf, and Directors of Speech and Hearing Programs in State Health and Welfare Agencies, endorses early detection of and intervention for infants with hearing loss through integrated, interdisciplinary state and national systems of universal newborn hearing screening, evaluation, and family-centered intervention.(5) Audiologic and medical evaluations should begin before three months of age. Infants with confirmed hearing loss should receive intervention before six months of age from health care and education professionals with expertise in hearing loss and deafness in infants and young children.(5,12,13)

The Centers for Disease Control and Prevention supports universal newborn hearing screening through its Early Hearing Detection and Intervention (EHDI) Program, which assists states in implementing screening and intervention programs and supports research and data collection on EHDI programs.(14) A 1993 National Institutes of Health Consensus Development Panel also recommended universal screening for hearing impairment before three months of age to identify and initiate treatment for all hearing-impaired infants by age six months.(15) A publication promoting the early identification of hearing loss has been published by the Maternal and Child Health Bureau of the Health Resources and Services Administration (HRSA). HRSA supports universal screening and has provided funding to assist states in developing such programs.(16)

The American Academy of Family Physicians and the Canadian Task Force on Preventive Health Care are currently reviewing their positions on universal newborn hearing screening.

The American College of Obstetricians and Gynecologists recommends screening for hearing loss in neonates with any of the following risk factors: family history of hereditary childhood SNHL, in utero infection, craniofacial anomalies, birth weight of less than 1,500 g, hyperbilirubinemia requiring exchange transfusion, ototoxic medications, bacterial meningitis, Apgar score of 0-4 at one minute or 0-6 at five minutes after birth, mechanical ventilation lasting five days or longer, or stigmata or other findings associated with a syndrome known to include a sensorineural or conductive hearing loss.(17)

The British National Coordinating Centre for Health Technology Assessment supports universal neonatal hearing screening, supplemented by a targeted infant distraction test at about seven months of age, primarily for children who were not screened neonatally.(18)

The USPSTF recommendations are independent of the U.S. government. They do not represent the views of the Agency for Healthcare Research and Quality (AHRQ), the U.S. Department of Health and Human Services, or the U.S. Public Health Service.

Address correspondence to Alfred O. Berg, M.D., M.P.H., Chair, U.S. Preventive Services Task Force, c/o David Atkins, M.D., M.P.H., Scientific and Technical Editor, U.S. Preventive Services Task Force, Agency for Healthcare Research and Quality, Center for Practice and Technology Assessment, 6010 Executive Blvd., Suite 300, Rockville, MD 20852 (e-mail:


(1.) U.S. Preventive Services Task Force. Guide to clinical preventive services. 2d ed. Baltimore: Williams & Wilkins, 1996.

(2.) Thompson DC, McPhillips H, Davis RL, Lieu TL, Homer CJ, Helfand M. Universal newborn hearing screening. Summary of evidence. JAMA 2001; 286:2000-10.

(3.) Helfand M, Thompson DC, Davis RL, McPhillips H, Homer CJ, Lieu TL. Newborn hearing screening. File Inventory, Systematic Evidence Review Number 5. AHRQ Publication No. 02-S001, October 2001. Rockville, Md.: Agency for Healthcare Research and Quality. Accessed November 1, 2001, at http://www.ahrq. gov/clinic/serfiles.htm.

(4.) Harrison M, Roush J. Age of suspicion, identification, and intervention for infants and young children with hearing loss: a national study. Ear Hear 1996;17:55-62.

(5.) Year 2000 position statement: principles and guidelines for early hearing detection and intervention programs. Joint Committee on Infant Hearing, American Academy of Audiology, American Academy of Pediatrics, American Speech-Language-Hearing Association and Directors of Speech and Hearing Programs in State Health and Welfare Agencies. Pediatrics 2000;106:798-817.

(6.) Fortnum H, Davis A. Epidemiology of permanent childhood hearing impairment in Trent Region, 1985-1993. Br J Audiol 1997;31:409-46.

(7.) Norton SJ, Gorga MP, Widen JE, Folsom RC, Sininger Y, Cone-Wesson B, et al. Identification of neonatal hearing impairment: evaluation of transient evoked otoacoustic emission, distortion product otoacoustic emission, and auditory brain stem response test performance. Ear Hear 2000;21:508-28.

(8.) Wessex Universal Neonatal Hearing Screening Trial Group. Controlled trial of universal neonatal screening for early identification of permanent childhood hearing impairment. Lancet 1998;352: 1957-64.

(9.) Vohr BR, Carty LM, Moore PE, Letourneau K. The Rhode Island Hearing Assessment Program: experience with statewide hearing screening (1993-1996). J Pediatr 1998;133:353-7.

(10.) Johnson JL, Kuntz NL, Sia CC, White KR, Johnson RL. Newborn hearing screening in Hawaii. Hawaii Med J 1997;56(12):352-5.

(11.) Prieve B, Dalzell L, Berg A, Bradley M, Cacace A, Campbell D, et al. The New York State universal newborn hearing screening demonstration project: outpatient outcome measures. Ear Hear 2000;21: 104-17.

(12.) Erenberg A, Lemons J, Sia C, Trunkel D, Ziring P. Newborn and infant hearing loss: detection and intervention. American Academy of Pediatrics. Task Force on Newborn and Infant Hearing, 1998-1999. Pediatrics 1999;103:527-30.

(13.) Pediatricians make new recommendations on hearing screening [press release]. American Academy of Pediatrics, April 5, 1999. Accessed November 1, 2001, at: archives/aprhear.htm.

(14.) Centers for Disease Control and Prevention, National Center for Birth Defects and Developmental Disabilities, Early Hearing Detection and Intervention Program. What is EHDI? Accessed October 15, 2001, at:

(15.) Early identification of hearing impairment in infants and young children. NIH Consens Statement 1993;11:1-24.

(16.) White K, Maxon A. Early identification of hearing loss: implementing universal newborn hearing screening programs. Rockville, Md.: Public Health Service, Health Resources and Services Administration, 1999. Accessed November 1, 2001, at: impguide.pdf

(17.) American Academy of Pediatrics, American College of Obstetricians and Gynecologists. Guidelines for perinatal care. 4th ed. Washington, D.C.: American College of Obstetricians and Gynecologists, 1997:160-2.

(18.) Department of Health. Piloting the introduction of universal neonatal hearing screening in England. Accessed November 1, 2001, at http://www.doh.

This is one in a series excerpted from the Recommendations and Rationale Statements released by the third U.S. Preventive Services Task Force (USPSTF). These statements address preventive health services for use in primary care clinical settings, including screening tests, counseling, and chemoprevention. The complete statement is available in HTML and PDF formats through the AFP Web site at www.aafp. org/afp/20011215/us. html. This statement is part of AFP's CME. See "Clinical Quiz" on page 1939.

COPYRIGHT 2001 American Academy of Family Physicians
COPYRIGHT 2002 Gale Group

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