Waardenburg syndrome
Encyclopedia
Waardenburg 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
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.
Major:
Minor:
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.
Symptoms vary from one type of the syndrome to another and from one patient to another, but they include:
Waardenburg syndrome has also been associated with a variety of other congenital disorder
s, such as intestinal
and spinal
defects, elevation of the scapula
, and cleft lip and palate. Sometimes this is concurrent with Hirschsprung disease.
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.
, '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.
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
most often characterized by varying degrees of deafness, minor defects in structures arising from the neural crest
Neural crest
Neural crest cells are a transient, multipotent, migratory cell population unique to vertebrates that gives rise to a diverse cell lineage including melanocytes, craniofacial cartilage and bone, smooth muscle, peripheral and enteric neurons and glia....
, and pigmentation anomalies.
It was first described in 1951
Eponyms and classification
Waardenburg syndrome is named after DutchNetherlands
The Netherlands is a constituent country of the Kingdom of the Netherlands, located mainly in North-West Europe and with several islands in the Caribbean. Mainland Netherlands borders the North Sea to the north and west, Belgium to the south, and Germany to the east, and shares maritime borders...
ophthalmologist
Ophthalmology
Ophthalmology is the branch of medicine that deals with the anatomy, physiology and diseases of the eye. An ophthalmologist is a specialist in medical and surgical eye problems...
Petrus Johannes Waardenburg
Petrus Johannes Waardenburg
Petrus Johannes Waardenburg was a Dutch ophthalmologist, geneticist, and pioneer in the application of genetics to ophthalmology...
(1886–1979), who described the syndrome in detail in 1951. The condition he described is now categorized as WS1. Swiss ophthalmologist David Klein
David Klein (ophthalmologist)
David Klein was a Swiss human geneticist and ophthalmologist.Klein graduating from the University of Basel in 1934. After graduating, he worked at the Rheinau Psychiatric Clinic, Zurich. He moved to Geneva as scientific assistant to professor Adolphe Franceschetti at the ophthalmological clinic....
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.
Signs and symptoms
There are five major and five minor diagnostic criteria for Waardenburg syndrome.Major:
- sensorineural hearing loss
- irisIris (anatomy)The iris is a thin, circular structure in the eye, responsible for controlling the diameter and size of the pupils and thus the amount of light reaching the retina. "Eye color" is the color of the iris, which can be green, blue, or brown. In some cases it can be hazel , grey, violet, or even pink...
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 canthiCanthusThe Canthus is either corner of the eye where the upper and lower eyelids meet.Canthus may also refer to:* Canthus of the eye, also called the orbital canthus* Canthus , the sides of the snout in reptiles in amphibians...
) - first‐degree relative previously diagnosed with Waardenburg syndrome
Minor:
- skin hypopigmentation (congenital leukoderma/white skin patches)
- medial eyebrow flare (synophrysUnibrowA unibrow is a "confluence of eyebrows"; that is, the presence of abundant hair between the eyebrows, so that they seem to converge to form one long eyebrow. The condition of having a unibrow is synophrys.-Beauty culture:...
) - broad nasal root
- hypoplasia alae nasi
- premature graying of the hair (before age 30).
Epidemiology
The overall incidence is ~1/42,000 — 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 Locus (genetics) In the fields of genetics and genetic computation, a locus is the specific location of a gene or DNA sequence on a chromosome. A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map... |
Also known as >- | Type I, WS1 |
PAX3 PAX3 PAX3 is a gene that belongs to the paired box family of transcription factors. This gene was formerly known as splotch. PAX3 has been identified with ear, eye and facial development. Mutations in it can cause Waardenburg syndrome types 1 and 3... |
2q35 | >- | MITF Microphthalmia-associated transcription factor Microphthalmia-associated transcription factor is a basic helix-loop-helix leucine zipper transcription factor involved in melanocyte and osteoclast development.-Clinical significance:... |
3p14.1-p12.3 | >- | WS2B WS2B WS2B is a gene associated with Waardenburg syndrome.... |
1p21-p13.3 | >- | WS2C | 8p23 | >- | SNAI2 SNAI2 Zinc finger protein SNAI2 is a protein that in humans is encoded by the SNAI2 gene.-Further reading:... |
8q11 | >- | PAX3 PAX3 PAX3 is a gene that belongs to the paired box family of transcription factors. This gene was formerly known as splotch. PAX3 has been identified with ear, eye and facial development. Mutations in it can cause Waardenburg syndrome types 1 and 3... |
2q35 | >- | EDNRB | 13q22 | >- | EDN3 | 20q13 | >- | SOX10 SOX10 Transcription factor SOX-10 is a protein that in humans is encoded by the SOX10 gene.... |
22q13 |
Symptoms
- Very pale or brilliantly blue eyes, eyes of two different colors (complete heterochromiaHeterochromiaIn anatomy, heterochromia refers to a difference in coloration, usually of the iris but also of hair or skin. Heterochromia is a result of the relative excess or lack of melanin...
), or eyes with one iris having two different colours (sectoral heterochromia); - A forelock of white hair (poliosisPoliosisPoliosis is the decrease or absence of melanin in head hair, eyebrows, or eyelashes. It can give rise to a "Mallen Streak" that can be hereditary....
), 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 telecanthusTelecanthusTelacanthus refers to increased distance between the medial canthi of the eyes, while the inter-pupillary distance is normal...
; - 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 skinSkin-Dermis:The dermis is the layer of skin beneath the epidermis that consists of connective tissue and cushions the body from stress and strain. The dermis is tightly connected to the epidermis by a basement membrane. It also harbors many Mechanoreceptors that provide the sense of touch and heat...
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 disorder
Congenital disorder
A congenital disorder, or congenital disease, is a condition existing at birth and often before birth, or that develops during the first month of life , regardless of causation...
s, such as intestinal
Intestine
In human anatomy, the intestine is the segment of the alimentary canal extending from the pyloric sphincter of the stomach to the anus and, in humans and other mammals, consists of two segments, the small intestine and the large intestine...
and spinal
Vertebral column
In human anatomy, the vertebral column is a column usually consisting of 24 articulating vertebrae, and 9 fused vertebrae in the sacrum and the coccyx. It is situated in the dorsal aspect of the torso, separated by intervertebral discs...
defects, elevation of the scapula
Scapula
In anatomy, the scapula , omo, or shoulder blade, is the bone that connects the humerus with the clavicle ....
, 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.
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 of its head or a solid white head 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, 75% of 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)Bones (TV series)
Bones is an American crime drama television series that premiered on the Fox Network on September 13, 2005. The show is based on forensic anthropology and forensic archaeology, with each episode focusing on an FBI case file concerning the mystery behind human remains brought by FBI Special Agent...
, '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
Peter May (writer)
Peter May is a Scottish television screenwriter, novelist and crime writer.- Early life :Peter was born in Glasgow. From an early age he was intent on becoming a novelist, but took up a career as a journalist as a way to start earning a living by writing. At the age of 21, he won the Fraser...
'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.
External links
- GeneReviews/NCBI/NIH/UW entry on Waardenburg Syndrome Type I
- OMIM Genetic disorder catalog — Waardenburg syndrome