WAARDENBURG SYNDROME (WS-I), KLEIN-WAARDENBURG SYNDROME (WS-3), CRANIOFACIAL-DEAFNESS-HAND SYNDROME (CDHS), PAX3 gene analysis

WAARDENBURG SYNDROME (WS-I)
KLEIN-WAARDENBURG SYNDROME (WS-3)
CRANIOFACIAL-DEAFNESS-HAND SYNDROME (CDHS)
PAX3 gene analysis

Approximately 1 in 1000 young children have a major hearing impairment (threshold >80dB). Significant hearing loss also occurs in about 1 in 25 people under age 45 and 1 in 10 by age 60 (threshold >25dB). Most of the hearing loss is genetic with over 30 autosomal recessive (70-80%), dominant (23-30%) and X-linked (2-3%) forms. Waardenberg syndrome type 1 (WS-1) is a major cause of syndromic, autosomal dominant hearing loss. However; variable expressivity may lead to underdiagnosis of this form of profound hearing loss. In Waardenburg Syndrome’s classical form the hearing loss can be accompanied by hypopigmentation resulting in a white forelock or pale iris but less than 50% of the patients exhibit the pigmentary disturbances. Mutations in the PAX3 gene (Paired Box Gene 3; chromosome 2q35) have been found in over 90% of individuals with WS-1; the remaining 10% may be a result of the deletion of the entire gene. The PAX3 gene is one of a family of DNA-binding transcription factors. Klein-Waardenberg Syndrome (WS-3) has overlapping physical characteristics with WS-1; however, WS-3 also can include limb anomalies such as flexion contractures, fusion of carpal bones and syndactyly. Additionally, Craniofacial-Deafness-Hand Syndrome (CDHS) has also been associated with mutations in the PAX3 gene. CDHS is a rare condition characterized by distinct flat facial features, profound hearing loss and hands with flexation contractures in the fingers,. The PAX3 protein also interacts with the MITF gene (see Waardenburg Syndrome, type 2) in an auditory-pigmentary developmental pathway.

REASONS FOR REFERRAL:

To determine whether a hearing defect in a child is hereditary.
To assess the risk of additional children with hearing loss in an affected family.
Prenatal testing.

TESTING METHODOLOGY:

Sequencing the entire coding sequence of the PAX gene will identify all published and unique familial mutations as well as examine the intron-exon borders.
Sequencing will identify 98% of the mutations in the coding region of the gene

SPECIMEN REQUIREMENTS:

Blood: EDTA (purple top) tubes (minimum 1-2 ml)
Prenatal testing: Please contact the laboratory for instructions

A Molecular Genetics Laboratory Test Requisition must accompany the specimen. Contact the Molecular Laboratory at 918-502-1721 or 866-846-0315 to obtain further information.

TURNAROUND TIME: 3 Weeks

CPT CODES: