Waardenburg syndrome

Waardenburg syndrome (also Waardenburg Shah Syndrome, WaardenburgKlein syndrome, Mende's syndrome II, Van der Hoeve-HalbertsmaWaardenburg syndrome, Ptosis-Epicanthus syndrome, Van der HoeveHalbertsma-Gualdi syndrome, Waardenburg type Pierpont,[5] Van der Hoeve-Waardenburg-Klein syndrome, Waardenburg's syndrome II and Vogts 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.

Eponyms and classification Waardenburg syndrome is named after Dutch ophthalmologist Petrus Johannes Waardenburg (18861979), who described the syndrome in detail in 1951.[1][2] The condition he described is now categorized as WS1. Swiss ophthalmologist David Klein also made contributions towards the understanding of the syndrome.[3] WS2 was identified in 1971, to describe cases where "dystopia canthorum" did not present.[4] WS2 is now split into subtypes, based upon the gene responsible. Other types have been identified, but they are less common. Signs and symptoms There are five major and five minor diagnostic criteria for Waardenburg syndrome. Major:

sensorineural hearing loss iris pigmentary abnormality (two eyes different color or iris bicolor or characteristic brilliant blue iris) hair hypopigmentation (white forelock or white hairs at other sites on the body) dystopia canthorum (lateral displacement of inner canthi) firstdegree relative previously diagnosed with Waardenburg syndrome

Minor:

skin hypopigmentation (congenital leukoderma/white skin patches) medial eyebrow flare (synophrys) broad nasal root 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 WaardenburgShah syndrome (association of Waardenburg syndrome with Hirschsprung disease). Type 4 is rare with only 48 cases reported up to 2002.[5] 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 Type I, WS1 193500 PAX3 Type IIa, WS2A (originally 193510 MITF WS2) Type IIb, WS2B 600193 WS2B Type IIc, WS2C 606662 WS2C Type IId, WS2D (very 608890 SNAI2 rare) Type III, WS3 Type IVa, WS4A Type IVb, WS4B Type IVc, WS4C 148820 PAX3 Locus 2q35 3p14.1p12.3 1p21-p13.3 8p23 8q11 2q35 Also known as Klein-Waardenburg syndrome

277580 EDNRB 13q22 613265 EDN3 20q13 613266 SOX10 22q13

Symptoms 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.

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. 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 animal will usually have a small white stripe along the top or back of its head, sometimes down the back of the neck (known as a blaze) or a solid white head (from nose to shoulders; ferrets with this are known as a panda marked ferret) and a somewhat,

although barely noticeably, flatter skull than normal ferrets. As a ferret's sense of hearing is poor to begin with it is not easily noticeable except for when the affected animal does not react to loud noises that non-affected ones will respond to. 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 (when compared to a standard sable/pole cat marked or albino ferret), 75% of US ferrets with a blaze or white head sold from pet stores are deaf

In Popular Culture In the season 6 episode of Bones (TV Series), '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 Mays.

Other Contributors

Waardenburg-Klein syndrome is named after Petrus Johannes Waardenburg (18861979), 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 GermanAmerican 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 (18861979). 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. Vogts syndrome is named for Cecile Vogt (1875-1962), a French-German neuropathologist.

See also

ChediakHigashi syndrome List of cutaneous conditions

References 1. ^ a b Waardenburg PJ (September 1951). "A new syndrome combining developmental anomalies of the eyelids, eyebrows and noseroot with pigmentary anomalies of the iris and head hair and with congenital deafness; Dystopia canthi medialis et punctorum lacrimalium lateroversa, hyperplasia supercilii medialis et radicis nasi, heterochromia iridum totaliis sive partialis, albinismus circumscriptus (leucismus, polioss) et surditas congenita (surdimutitas)". Am. J. Hum. Genet. 3 (3): 195253. PMC 1716407. PMID 14902764. 2. ^ doctor/1012 at Who Named It? 3. ^ Klein-Waardenburg syndrome at Who Named It? 4. ^ Arias S (1971). "Genetic heterogeneity in the Waardenburg syndrome". Birth Defects Orig. Artic. Ser. 07 (4): 87101. PMID 5006208. 5. ^ Egbalian F (2008). "Waardenburg Shah syndrome; A case report and review of the literature". Iran J Ped 18 (1): 717. 6. ^ Erika Matulich, Ph.D, Cypresskeep.com External links

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