OMIM ID:
Waardenburg Syndrome, Type 3
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Type 3 Waardenburg syndrome has many of the features of other types but with the addition of upper limb anomalies. Dystopia canthorum and a broad nasal root are characteristic. Iris heterochromia is present in some patients. Hypopigmentation may be seen in lashes and eyebrows.
Systemic Features
The upper limbs may appear underdeveloped with flexion contractures, fusion of the carpal bones and sometimes syndactyly. A white forelock may or may not be present. The cranial bones may be anomalous and rare patients can have microcephaly with significant mental retardation. Mental function is usually normal though. Occasional patients have cleft palate and/or lip. Hearing loss is of the sensorineural type. Hypopigmented skin patches are sometimes present but not all patients have them.
Genetics
Inheritance
The uniqueness of Waardenburg syndrome types 1 and 3 remains to be established. Mutations in the PAX3 gene are responsible for both types and both have been found in the same family. The phenotype is transmitted in an autosomal dominant pattern in either case but several families have been reported with type 1 WS in parents heterozygous for PAX3 mutations who had a homozygous child with the type 3 phenotype. However, heterozygous individuals with type 3 have also been reported and the relationship of the two types remains unknown.
Craniofacial-deafness-hand syndrome(122880) with mutations in PAX3 has many features similar to those found in Waardenburg syndrome type 3 and may or may not be a unique disorder.
Pedigree
Autosomal dominant
Autosomal dominant disorders require only one mutation for the disease to be expressed. Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease. It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).
Autosomal dominant inheritance leads to a vertical pattern of transmission
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.