Waardenburg Syndrome

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What is Waardenburg syndrome?

Waardenburg syndrome is a group of genetic conditions that can cause hearing loss and changes in coloring (pigmentation) of the hair, skin, and eyes. Although most people with Waardenburg syndrome have normal hearing, moderate to profound hearing loss can occur in one or both ears. People with this condition often have very pale blue eyes or different colored eyes, such as one blue eye and one brown eye. Sometimes one eye has segments of two different colors. Distinctive hair coloring (such as a patch of white hair or hair that prematurely turns gray) is another common sign of the condition. The features of Waardenburg syndrome vary among affected individuals, even among people in the same family.

The four known types of Waardenburg syndrome are distinguished by their physical characteristics and sometimes by their genetic cause. Types I and II have very similar features, although people with type I almost always have eyes that appear widely spaced and people with type II do not. In addition, hearing loss occurs more often in people with type II than in those with type I. Type III (sometimes called Klein-Waardenburg syndrome) includes abnormalities of the upper limbs in addition to hearing loss and changes in pigmentation. Type IV (also known as Waardenburg-Shah syndrome) has signs and symptoms of both Waardenburg syndrome and Hirschsprung disease, an intestinal disorder that causes severe constipation or blockage of the intestine.

How common is Waardenburg syndrome?

Waardenburg syndrome affects an estimated 1 in 10,000 to 20,000 people. In schools for the deaf, 2 percent to 3 percent of students have this condition. Types I and II are the most common forms of Waardenburg syndrome, while types III and IV are rare.

What genes are related to Waardenburg syndrome?

Mutations in the EDN3, EDNRB, MITF, PAX3, SNAI2, and SOX10 genes cause Waardenburg syndrome.

The genes that cause Waardenburg syndrome are involved in the formation and development of several types of cells, including pigment-producing cells called melanocytes. Melanocytes make a pigment called melanin, which contributes to skin, hair, and eye color and plays an essential role in the normal function of the inner ear. Mutations in any of these genes disrupt the normal development of melanocytes, leading to abnormal pigmentation of the skin, hair, and eyes and problems with hearing.

Types I and III Waardenburg syndrome are caused by mutations in the PAX3 gene. Mutations in the MITF and SNAI2 genes are responsible for type II Waardenburg syndrome.

Mutations in the SOX10, EDN3, or EDNRB genes cause type IV Waardenburg syndrome. In addition to melanocyte development, these genes are important for the development of nerve cells in the large intestine. Mutations in any of these genes result in hearing loss, changes in pigmentation, and intestinal problems related to Hirschsprung disease.

How do people inherit Waardenburg syndrome?

Waardenburg syndrome is usually inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell 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 in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.

Source: National Institutes of Health

Study findings from Texas A&M University, Center for Environmental and Genetic Medicine provide new insights into spina bifida genetics

"Mutations in the murine homologue, pax3, are responsible for the phenotype of splotch mice, in which nullizygotes are 100% penetrant for NTDs. The study sample included 74 infants with spina bifida (cases) and 87 nonmalformed infant controls. The conserved paired-box domain as well as the upstream genomic region of PAX3 were subjected to resequencing and those identified SNPs were evaluated as haplotypes. The associations of haplotypes for selected gene regions and the risks of spina bifida were further studied. Nineteen SNPs were observed; 15 observed in controls had been submitted to the National Center for Biotechnology Information (NCBI) database with allele frequencies. The PAX3 gene variant T-1186C (rs16863657) and its related haplotype, TCTCCGCCC of nine SNPs, were found to be associated with an increased risk of spina bifida, with an OR of 3.5 (95% CI: 1.2-10.0) among Hispanic Whites. Our analyses indicated that PAX3 SNPs were not strong risk factors for human spina bifida," wrote W. Lu and colleagues, Texas A&M University, Center for Environmental and Genetic Medicine.

The researchers concluded: "However, additional follow-up of the PAX3 gene variant T-1186C (rs16863657) and its related haplotype, TCTCCGCCC, may be important in other populations."

Lu and colleagues published their study in Birth Defects Research Part a (Screening for novel PAX3 polymorphisms and risks of spina bifida. Birth Defects Research Part a, 2007;79(1):45-9).

For additional information, contact W. Lu, Center for Environmental and Genetic Medicine, Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, Texas 77030 and Children's Hospital Oakland Research Institute, CA USA.

Publisher contact information for the journal Birth Defects Research Part a is: Wiley-Liss, Division John Wiley & Sons Inc., 111 River St., Hoboken, NJ 07030, USA.

Keywords: United States, Houston, Spina Bifida Genetics, Biotechnology, Genetics, Spina Bifida, Spinal Dysraphism.

This article was prepared by Pain & Central Nervous System Week editors from staff and other reports. Copyright 2007, Pain & Central Nervous System Week via NewsRx.com.