Waardenburg Syndrome (WS) is divided into four distinct clinical subtypes, one of them being Klein-Waardenburg Syndrome (type 3), which is described as an extreme variant of the classical WS type 1 [1] [2] [3]. Across all WS types, however, symptoms stem from the absence of melanocytes from the skin, eyes, hair and stria vascularis of the cochlea [1] [3]. Congenital sensorineural hearing loss - typically non-progressive, either unilateral or bilateral, and dystopia canthorum (fusion of medial eyelids and the appearance of a blepharophimosis) are observed in the majority of WS type 1 patients [1]. Moreover, heterochromia iridis (segmental or total and either unilateral or bilateral), skin and hair hypopigmentation, a white forelock, early graying of the hair (before 30 years of age) and white skin patches (known as congenital leukoderma) on the trunk, limbs or face are other notable signs [1] [2]. To distinguish Klein-Waardenburg syndrome from other WS variants, musculoskeletal abnormalities should be noted in addition to the mentioned symptoms [1] [4] [5]. Namely, carpal bone fusion, syndactyly, and hypoplasia or contractures of the joints or limb muscles (more commonly the arms) are the main characteristics of this subtype [1] [2].

• Short Stature

  Short stature; brachycephaly with shortening of the front part of the base of the skull; jaw and tooth position anomalies. Eye involvement with hyperopia and astigmatism (more rarely) as well as further pigment anomalies at the ocular fundus. [altmeyers.org]

  Other clinical features include a moderate acrocephaly, lack of osseous fusion of the short tubular bones, oligodactyly of the feet, short stature, cyanotic cardiopathy, laryngomalacia, pericardial cysts, rectal prolapse, and deformed ears. [accesspediatrics.mhmedical.com]

  stature, bone density reduction, epilepsy, and cryptorchidism. [researchmap.jp]

• Overeating

  Benefit from the experience of over 60 contributors from around the world lead by Drs. Lawrence F. Eichenfield and Ilona J. Frieden, two of the most important names in the fields of dermatology and pediatrics. [books.google.de]

  Molecular genetic testing available by sequencing the PAX3 gene (chromosomal locus 2q35) can be used to confirm the diagnosis in atypical cases primarily used for genetic counseling of at-risk family members detects over 90% of disease-causing mutations [en.wikibooks.org]

  Other systemic findings in this patient were- flat nasal bridge, premature graying of hairs, patchy hyperpigmented spots over face and trunk, discoloured nails (melanonychia), mild splenomegaly with evidence of megaloblastic anemia on peripheral blood [djo.org.in]

  There is no way to predict how Waardenburg syndrome will manifest or change over time in a given person. However, knowing the type of Waardenburg syndrome a person has can help doctors plan appropriate treatment. [medicalnewstoday.com]

  He went on to study over a thousand individuals in deaf families and found that some of them had certain physical characteristics in common. One commonly observed characteristic of Waardenburg syndrome is two differently colored eyes. [healthfully.org]

• Failure to Thrive

  […] gain weight at the expected rate (failure to thrive); and/or other abnormalities. [rarediseases.org]

• Jaundice

  Bilateral absent posterior semicircular canals have been reported with WS, Alagellie syndrome, CHARGE syndrome, and Goldenhaar syndrome. [1], [2] Alagellie syndrome is characterized by cholestatic jaundice due to paucity of intrahepatic biliary radicals [indianjotol.org]

• Hearing Impairment

  For example, a person with WS may have a white forelock, a patch of white hair near the forehead, and no hearing impairment. Others may have white patches of skin and severe hearing impairment. [healthfully.org]

  Management of Deafness or Hearing Impairment Once diagnosed with Waardenburg syndrome, the child or infant must begin with programs to manage the hearing impairment. [syndromespedia.com]

  About 20 percent of patients also have hearing impairment. WS2 - When other WS symptoms are present without the wide-set eyes, patients are considered to have WS2. Approximately 50 percent of WS2 patients have a hearing impairment or are deaf. [empowher.com]

  Affiliated tissues include eye, skin and bone, and related phenotypes are hearing impairment and joint stiffness Disease Ontology : 12 A Waardenburg's syndrome characterized by upper limb anomalies, congenital hearing loss, dystopia canthorum and pigmentation [malacards.org]

  The syndrome is named for a Dutch eye doctor named Petrus Johannes Waardenburg (1886-1979) who first noticed that people with differently colored eyes often had a hearing impairment. [medicinenet.com]

• Hearing Problem

  Hearing should be checked closely. Outlook (Prognosis) Once hearing problems are corrected, most people with this syndrome should be able to lead a normal life. Those with rarer forms of the syndrome may have other complications. [baptistjax.com]

  Possible Complications Complications may include: Constipation severe enough to require part of large bowel to be removed Hearing loss Self-esteem problems, or other problems related to appearance Slight decreased intellectual functioning (possible, unusual [account.allinahealth.org]

• Premature Graying of the Hair

  Also, the presence of peliosis (white forelock) or premature graying of the hair is the characteristic of the disease. [accesspediatrics.mhmedical.com]

  […] corner of the eye displaced to the side (dystopia canthorum) Minor criteria: Patches of light or white skin Eyebrows extending toward middle of face Nose abnormalities Premature graying of the hair (by age 30) Waardenburg syndrome type 2 is defined as [verywell.com]

  Hypopigmented eyes, hair and skin – White pigmentations can be present in the skin, a lock of gray or white hair growing prematurely can be seen, and a pale color of eyes is noted and the color can be different in both eyes. [syndromespedia.com]

  Minor criteria include skin hypopigmentation (congenital leukoderma/ white skin patches), medial eyebrow flare (synophrys), broad nasal root, hypoplasia alae nasi, and premature graying of the hair. [panafrican-med-journal.com]

  Her father and her siblings also have a white forelock with premature graying of hair [Figure 1]. [indianjnephrol.org]

• Skin Disease

  Vogt-Koyanagi-Harada syndrome: a disease complex affecting the eyes, skin, auditory system and central nervous system. Rare in white-skinned individuals. Autoimmune disease. [dermatologyadvisor.com]

  diseases See the DermNet NZ bookstore. [dermnetnz.org]

• Hypertelorism

  The patient showed pigmentation abnormalities of the right iris, ocular hypertelorism (W index: 2.00), right-sided congenital hearing loss, synophrys, incomplete left cleft lip, and cryptorchidism. [nature.com]

  More rarely, there is also genuine hypertelorism and hyperplasia of the medial part of the eyebrows as well as hyperplasia of the bony part of the nose with broad, high nasal root. [altmeyers.org]

  […] hereditary nephritidis Patients develop glomerulonephritis that progresses to renal failure Some patients develop hearing loss 10% have eye abnormalities such as cataracts Leopard Syndrome Autosomal dominant Presenation lentigines EKG abnormalities ocular hypertelorism [medbullets.com]

  Dystopia canthorum is a prominent and nearly constant (>95%) feature of type 1, and together with the prominent nasal root and increased intercanthal distance may suggest hypertelorism. [disorders.eyes.arizona.edu]

• Vertigo

  Vestibular symptoms including vertigo, dizziness and balance problems have been reported in Waardenburg Syndrome, even without hearing loss. [californiaearinstitute.com]

To make the diagnosis of Klein-Waardenburg syndrome, physicians must recognize all signs and symptoms of the condition. Therefore, a detailed physical examination must be conducted. In fact, criteria for the diagnosis of WS type 1 are based solely on clinical findings [1] [2], and the additional presence of symptoms characteristic for Klein-Waardenburg syndrome can confirm the diagnosis. Notable features of the remaining WS types, 2 and 4, such as the absence of dystopia canthorum or presence of the appearance of Hirschsprung disease should be detected or excluded during workup [1]. A thorough patient history is an equally important part of the diagnostic workup since an autosomal dominant pattern of inheritance is the underlying mechanism of the disease [1] [5] [3]. However, many individuals with confirmed Klein-Waardenburg syndrome develop mutations in a sporadic fashion [1] [5], which is why genetic testing for identification of specific mutations should be carried out once valid clinical criteria exist. Detection of PAX3 mutations on the distal long arm of chromosome 2 through sequence analysis is considered diagnostic for WS type 1, and consequently, type 3 [1] [2].

Treatment Treatment Options: No ocular treatment is necessary. Patients may benefit from cochlear implants. [disorders.eyes.arizona.edu]

Exams and Tests Tests may include: Audiometry Bowel transit time Colon biopsy Genetic testing Treatment There is no specific treatment. Symptoms will be treated as needed. [pennstatehershey.adam.com]

The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment. [orpha.net]

Additionally, candidacy for cochlear implantation, currently the only medical treatment available for the treatment of profound sensorineural hearing loss, cannot be established without a comprehensive medical examination. [californiaearinstitute.com]

Prognosis Due to the very few number of cases described so far, information on prognosis and quality of life is limited. Disease progression is variable, with symptoms being more severe in homozygous than in heterozygous forms. [rarediseases.info.nih.gov]

Etiology WS3 is caused by heterozygous or homozygous mutations in the PAX3 (2q36.1) gene. Diagnostic methods Diagnosis is made through criteria of the association of WS1 manifestations with limb anomalies. [rarediseases.info.nih.gov]

Qualifiers English: BL blood CF cerebrospinal fluid CI chemically induced CL classification CO complications DI diagnosis DG diagnostic imaging DH diet therapy DT drug therapy EC economics EM embryology EN enzymology EP epidemiology EH ethnology ET etiology [decs.bvs.br]

Epidemiology Incidence is unknown, but WS3 is the rarest form of all Waardenburg syndrome types. [rarediseases.info.nih.gov]

Chapters on epidemiology, embryology, non-syndromic hearing loss, and syndromic forms of hearing loss have all been updated with particular attention to the vast amount of new information on molecular mechanisms, and chapters on clinical and molecular [books.google.de]

Syndrome 1991-2012 Allowable Qualifiers English: BL blood CF cerebrospinal fluid CI chemically induced CL classification CO complications DI diagnosis DG diagnostic imaging DH diet therapy DT drug therapy EC economics EM embryology EN enzymology EP epidemiology [decs.bvs.br]

You might also be interested in Dermatology Occurrence/Epidemiology This section has been translated automatically. Prevalence: 1-2/100.000 Etiopathogenesis This section has been translated automatically. [altmeyers.org]

The pigmentary system: physiology and pathophysiology. 2006. pp. 541-50. [dermatologyadvisor.com]

Pathophysiology WS is a genetic disorder with autosomal dominant inheritance.[5] There are various hypotheses proposed about the pathogenesis and to explain the different types and clinical features. [statpearls.com]

Transcriptional regulation of gene expression: mechanisms and pathophysiology. Hum. Mutat. 3, 180–199 (1994). 8 Tassabehji, M. et al. Waardenburg's syndrome patients have mutations in the human homologue of the Pax-3 paired box gene. [nature.com]

[…] diet therapy DT drug therapy EC economics EM embryology EN enzymology EP epidemiology EH ethnology ET etiology GE genetics HI history IM immunology ME metabolism MI microbiology MO mortality NU nursing PS parasitology PA pathology PP physiopathology PC prevention [decs.bvs.br]

Prevention How can I prevent Waardenburg syndrome? There's no way to prevent Waardenburg syndrome since a genetic mutation causes the condition. [my.clevelandclinic.org]

Genetic Counseling Waardenburg syndrome can be prevented by genetic counseling. [syndromespedia.com]

Prevention Genetic counseling may be valuable for prospective parents with a family history of Waardenburg syndrome. Alternative Names Klein-Waardenburg syndrome; Waardenburg-Shah syndrome [dxline.info]

1. Read AP, Newton VE. Waardenburg syndrome. J Med Genet. 1997;34(8):656-665.
2. Milunsky JM. Waardenburg Syndrome Type I. 2001 [Updated 2014 Aug 7]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016.
3. Choi JH, Moon SK, Lee KH, Lew HM, Chang YH. Three cases of Waardenburg syndrome type 2 in a Korean family. Korean J Ophthalmol. 2004;18(2):185-189.
4. Pingault V, Ente D, Dastot-Le Moal F, Goossens M, Marlin S, Bondurand N. Review and update of mutations causing Waardenburg syndrome. Hum Mutat. 2010;31(4):391-406.
5. Tekin M, Bodurtha JN, Nance WE, Pandya A. Waardenburg syndrome type 3 (Klein-Waardenburg syndrome) segregating with a heterozygous deletion in the paired box domain of PAX3: a simple variant or a true syndrome? Clin Genet. 2001;60(4):301-304.