Waardenburg syndrome

ワールデンブルグ症候群

WordNet

1. a pattern of symptoms indicative of some disease
2. a complex of concurrent things; "every word has a syndrome of meanings"

PrepTutorEJDIC

1. (疾患の徴候となる一群の)症徴候,症候群 / (事件・社会的状態などのパターンを示す)徴候形態

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/26 14:28:46」(JST)

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Waardenburg syndrome
Classification and external resources
Specialty	endocrinology
ICD-10	E70.3 (ILDS E70.32)
ICD-9-CM	270.2
DiseasesDB	14021 33475
MedlinePlus	001428
eMedicine	ped/2422 derm/690
NCI	Waardenburg syndrome
MeSH	D014849

Waardenburg syndrome (also Waardenburg Shah Syndrome, Waardenburg-Klein syndrome) is a rare genetic disorder most often characterized by varying degrees of deafness, minor defects in structures arising from the neural crest, and pigmentation anomalies.

It was first described in 1951.

Eponyms and classification

Waardenburg syndrome is named after Dutch ophthalmologist Petrus Johannes Waardenburg (1886–1979), who described the syndrome in detail in 1951. The condition he described is now categorized as WS1. Swiss ophthalmologist David Klein also made contributions towards the understanding of the syndrome.

WS2 was identified in 1971, to describe cases where "dystopia canthorum" did not present. WS2 is now split into subtypes, based upon the gene responsible.

Other types have been identified, but they are less common.

Mutations in the EDN3, EDNRB, MITF, PAX3, SNAI2, and SOX10 are the genes that are affected from Waardenburg Syndrome. Some of these genes are involved in the making of melanocytes, which makes the pigment melanin. Melanin is an important pigment in the development of hair, eye color, skin, and functions of the inner ear. So the mutation of these genes can lead to abnormal pigmentation and hearing loss. PAX3 and MTIF gene mutation occurs in type I and II (WS1 and WS2). Type III (WS3) shows mutations of the PAX3 gene also. SOX10, EDN3, or EDNRB gene mutations occur in type IV. Type IV (WS4) can also affect portions of nerve cell development that potentially can lead to intestinal issues.

Signs and symptoms

There are five major and five minor diagnostic criteria for Waardenburg syndrome.

Major:

• sensorineural hearing loss
• iris pigmentary abnormality ( heterochromia iridum- different colors of iris in two eyes or heterochromia iridis - two different colors of iris in same eye or characteristic brilliant blue iris)
• hair hypopigmentation (white forelock or white hairs at other sites on the body) (poliosis)
• dystopia canthorum (lateral displacement of inner canthi)
• first‐degree relative previously diagnosed with Waardenburg syndrome

Minor:

• skin hypopigmentation (congenital leukoderma/white skin patches - Vitiligo )
• medial eyebrow flare (synophrys)
• broad nasal root (dystopia canthorum)
• hypoplasia alae nasi
• premature graying of the hair (before age 30).

Epidemiology

The overall incidence is ~1/42,000 to 1/50,000 people. Types I and II are the most common types of the syndrome, whereas types III and IV are rare. Type 4 is also known as Waardenburg‐Shah syndrome (association of Waardenburg syndrome with Hirschsprung disease).

Type 4 is rare with only 48 cases reported up to 2002.

About 1 in 30 students in schools for the deaf have Waardenburg syndrome. All races and both sexes are affected equally. The highly variable presentation of the syndrome makes it difficult to arrive at precise figures for its prevalence.

Classification

Subtypes of the syndrome are traceable to different genetic variations:

Type	OMIM	Gene	Locus	Also known as
Type I, WS1	193500	PAX3	2q35	-
Type IIa, WS2A (originally WS2)	193510	MITF	3p14.1-p12.3	-
Type IIb, WS2B	600193	WS2B	1p21-p13.3	-
Type IIc, WS2C	606662	WS2C	8p23	-
Type IId, WS2D (very rare)	608890	SNAI2	8q11	-
Type III, WS3	148820	PAX3	2q35	Klein-Waardenburg syndrome
Type IVa, WS4A	277580	EDNRB	13q22
Type IVb, WS4B	613265	EDN3	20q13
Type IVc, WS4C	613266	SOX10	22q13

Symptoms

Facial morphology of Waardenburg syndrome

Symptoms vary from one type of the syndrome to another and from one patient to another, but they include:

• Very pale or brilliantly blue eyes, eyes of two different colors (complete heterochromia), or eyes with one iris having two different colours (sectoral heterochromia);
• A forelock of white hair (poliosis), or premature graying of the hair;
• Appearance of wide-set eyes due to a prominent, broad nasal root (dystopia canthorum)—particularly associated with type I) also known as telecanthus;
• Moderate to profound hearing loss (higher frequency associated with type II);
• A low hairline and eyebrows that touch in the middle.
• Patches of white pigmentation on the skin have been observed in some people. Sometimes, abnormalities of the arms, associated with type III, have been observed.
• Type IV may include neurologic manifestations.

Waardenburg syndrome has also been associated with a variety of other congenital disorders, such as intestinal and spinal defects, elevation of the scapula, and cleft lip and palate. Sometimes this is concurrent with Hirschsprung disease.

Type I is associated with more permanent hearing loss; in Type III hearing will be lost over time. Both are similar physically, but they are phenotypically identical. To distinguish the differences between the two types, genetic testing is needed. Type II is most common, with permanent hearing loss and heterochromia of the irises (two different colored eyes) being the major signs. In Type IV, symptoms are similar to those associated with type II, but patients additionally tend to develop Hirschsprung's disease, which can be life-threatening and requires surgery if the colon is enlarged.

Inheritance

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.

• Waardenburg syndrome is usually inherited in an autosomal dominant pattern.

• Types II and IV Waardenburg syndrome may sometimes have an autosomal recessive pattern of inheritance.

Types I and III inheritance of this trait is autosomal dominant. If an affected parent is homozygous dominant there is a 100% that the child will be affected and if the affected parent is heterozygous dominant then there is a 50% chance that a child of an affected parent will be affected. Symptoms vary and so the extremity of symptoms cannot be determined. Types II and IV is autosomal recessive, symptoms are not definite they vary just as the other type’s symptoms will. A study was done on a rare case of a double heterozygous child with each parent having only single mutations in MTIF or PAX3. The effect of double heterozygous mutations in the genes MTIF and PAX3 in WS1 and WS2 can increase the pigment-affected symptoms. It leads to the conclusion that the double mutation of MTIF is associated with the extremity of Waardenburg Syndrome and may affect the phenotypes or symptoms of the syndrome

Treatment

There is currently no treatment or cure for Waardenburg syndrome. The symptom most likely to be of practical importance is deafness, and this is treated as any other irreversible deafness would be. In marked cases there may be cosmetic issues. Other abnormalities (neurological, structural, Hirschsprung disease) associated with the syndrome are treated symptomatically.

In animals

Waardenburg syndrome is known to occur in ferrets. The affected individual will usually have a small white stripe along the top or back of the head and sometimes down the back of the neck (this is known as a "blaze" coat pattern), or a solid white head from nose to shoulders (known as a "panda" coat pattern). The ferret will often have a very slightly flatter skull than ferrets without the syndrome and may have unusually wide-set eyes. As a ferret's sense of hearing is poor to begin with, associated deafness is not easily noticeable except for a lack of reaction to loud noises. As the disorder is easily spread to offspring, the affected animal will not be used for breeding by private, reputable breeders, although it may still be neutered and sold as a pet. However, largely as a result of mass-breeding due to the "exotic" markings it gives, 75% of US ferrets with a blaze or white head sold from pet stores are deaf.

Domesticated cats with blue eyes and white coats are often completely deaf. Whether or not this is a result of Waardenburg syndrome remains unclear. Deafness is far more common in white cats than in those with other coat colors. According to the ASPCA Complete Guide to Cats, "17 to 20 percent of white cats with nonblue eyes are deaf; 40 percent of "odd-eyed" white cats with one blue eye are deaf; and 65 to 85 percent of blue-eyed white cats are deaf." In the 1980's, college genetic classes taught that the genes for deafness and white coat color were closely linked, resulting in the majority of cats with completely white coats and bluer eyes being deaf. The newer evidence cited above refutes this simplistic idea.

In popular culture

In the season 6 episode of Bones, 'The Signs in the Silence', the team must solve a case in which the suspected killer has Waardenburg syndrome.

Enzo Macleod, protagonist of Peter May's series The Enzo Files, has Waardenburg syndrome. His eyes are different colors and he has a white streak in his hair. See pp. 17-18 of Extraordinary People (2006) by Peter May.

The book Reconstructing Amelia by Kimberly McCreight features several characters with Waardenburg symptoms.

The book Closer Than You Think by Karen Rose features three characters, siblings, with Waardenburg Syndrome.

Other contributors

• Waardenburg-Klein syndrome is named after Petrus Johannes Waardenburg (1886–1979), a Dutch ophthalmologist and geneticist, and David Klein, a Swiss human geneticist and ophthalmologist.
• Mende's syndrome II is named after Irmgard Mende (1938–), a German-American physician.
• Van der Hoeve-Halbertsma-Waardenburg Syndrome is named after Jan Van der Hoeve (1878-1952), a Dutch ophthalmologist, Nicolaas Adolf Halbertsma (1889-1968), Dutch physician and Petrus Johannes Waardenburg (1886–1979).
• Van der Hoeve-Halbertsma-Gualdi syndrome is named for Jan Van der Hoeve (1878–1952), Nicolaas Adolf Halbertsma (1889–1968) and Vincenzo Gualdi (1891–1976),an Italian physician.
• Vogt’s syndrome is named for Cecile Vogt (1875–1962), a French-German neuropathologist.

See also

• Chediak–Higashi syndrome
• List of cutaneous conditions

References

External links

• GeneReviews/NCBI/NIH/UW entry on Waardenburg Syndrome Type I
• OMIM Genetic disorder catalog — Waardenburg syndrome

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 遺伝性皮膚症 the genodermatoses
• 2. 小児における聴覚障害：病因 hearing impairment in children etiology
• 3. 消化管の発達に関する概要 overview of the development of the gastrointestinal tract
• 4. 新生児における難聴スクリーニング screening the newborn for hearing loss
• 5. 小児における聴覚障害：評価 hearing impairment in children evaluation

English Journal

• Pigmentary disorders of the eyes and skin.

• Que SK1, Weston G1, Suchecki J2, Ricketts J3.
• Clinics in dermatology.Clin Dermatol.2015 Mar-Apr;33(2):147-58. doi: 10.1016/j.clindermatol.2014.10.007.
• Oculocutaneous albinism, Menkes syndrome, tuberous sclerosis, neurofibromatosis type 1, dyskeratosis congenita, lentiginosis profusa syndrome, incontinentia pigmenti, and Waardenburg syndrome all are genodermatoses that have well established gene mutations affecting multiple biological pathways, inc
• PMID 25704935

• Case report: waardenburg syndrome.

• Dumayas GL1, Capó-Aponte JE2.
• Military medicine.Mil Med.2015 Mar;180(3):e381-7. doi: 10.7205/MILMED-D-14-00430.
• PURPOSE: A case of Waardenburg syndrome type 1 is described and relevant literature is reviewed to raise awareness about this rare syndrome, including the classification of each subtype and the differentiating clinical manifestations.CASE REPORT: A 44-year-old African-American female presented for a
• PMID 25735036

• [Construction and analysis of recombinant eukaryotic expression plasmids for SOX10, the causative gene of Warrdenburg syndrome].

• Zhang H1, Feng J, Chen H, Li J, Luo H, Feng Y.
• Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics.Zhonghua Yi Xue Yi Chuan Xue Za Zhi.2015 Feb 10;32(1):49-55. doi: 10.3760/cma.j.issn.1003-9406.2015.01.011.
• OBJECTIVE To study the exogenous expression and subcellular localization of wild type (WT) and mutant SOX10 proteins in vitro through generation of expression plasmids in order to reveal the pathogenesis of Waardenburg syndrome (WS). METHODS The plasmids pECE-SOX10 and pCMV-Flag were ligated after t
• PMID 25636099

Japanese Journal

• 一般口演「先天異常」 西葛西井上眼科こどもクリニックにて経験したWaardenburg症候群の同胞例 (第36回 日本小児眼科学会)

• 宮崎 紀行,岩？ 一絵,宮田 真由美 [他]
• 眼科臨床紀要 5(4), 373-376, 2012-00-00
• NAID 40019293789

• Genetic Background Strongly Modifies the Severity of Symptoms of Hirschsprung Disease, but not Hearing Loss in Rats Carrying Ednrb^[sl] Mutations

• Dang Ruihua,Torigoe Daisuke,Suzuki Sari,Kikkawa Yoshiaki,Moritoh Kanako,Sasaki Nobuya,Agui Takashi
• PLoS One 6(9), e24086, 2011-09-07
• … Moreover, we found that this mutation results in serious congenital sensorineural deafness, and these strains may be used as ideal models of Waardenburg Syndrome Type 4 (WS4). … Furthermore, we evaluated how the same changed genetic background modifies three features of WS4 syndrome, aganglionosis, hearing loss, and pigment disorder in these congenic strains. … This study will help us to better understand complicated diseases such as HSCR and WS4 syndrome. …
• NAID 120003370691

Related Links

• Waardenburg syndromeとは - goo Wikipedia (ウィキペディア)

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• Waardenburg syndrome: MedlinePlus Medical Encyclopedia

Waardenburg syndrome is usually inherited as an autosomal dominant trait, meaning only one parent has to pass on the faulty gene for a child to be affected. There are four main types of Waardenburg syndrome. The ...

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リンク元	「ワールデンブルグ症候群」「Waardenburg's syndrome」
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