What is connexin 26 gene? What is its importance in Congenital Hearing Loss? What is a abiotrophy and how does it present in the ear?
Around 70% of genetic hearing loss are non-syndromic hearing loss. A number of gene mutations are thought to be responsible for non-syndromic hearing loss. Many of these have recently been identified. The disordered DFNB1, caused by mutation in the CJB2 gene which encodes for the protein connexin 30, accounts for 50% of autosomal recessive non syndromic hearing loss.
The carrier rate in the general population for a recessive deafness causing GJB2 mutation is about 1 in 33(Smith RJ etal)
It is current practice the families of all children with severe/ profound hearing loss are offered genetic screening for these two mutations.
Establishing a molecular diagnosis of GJb2- related deafness is important clinically since these children can avoid further diagnostic test. They are not at increased risk for medical co-morbidity. In general, bony abnormalities of the cochlea are not part of this deafness phenotype and developmental motor milestones and vestibular function are normal.
The hearing loss associated with GJB2 related deafness can vary from mild to profound.
The diagnostic yeild of GJB2 screen is significantly higher in patients with severe to profound sensorineural hearing loss(SNHL) than in all other groups.
Preciado et al suggested that a cost effective approach to screening would be to test children with severe – profound SNHL c a GJB2 screen as opposed to those with milder SNHL who should undergo imaging as the initial testing step.
For children with GJB2 related (connexin) severe to profound deafness sibling with identical GJB2 generate have a 91% chance of having severe to profound deafness and a 9% chance of having mild to moderate deafness.
For children with CJB2 related deafness and mild to moderate deafness sibling with identical GJB2 genotype have a 66% chance of having mild to moderate deafness and 34% chance of having severe to profound deafness.
If the deaf child does not have DFNB1 based on molecular genetic testing of GJB2 (which codes for the protein connexin 26) the recurrence risk is 14% for deafness unrelated to connexin 26.