A retrospective study was undertaken to answer the following questions: Is the sensorineural hearing loss (SNHL) in Turner syndrome progressive? Can the occurrence of hearing loss be explained by the parental origin of the intact X chromosome? Twenty-four individuals recruited through the Turner Syndrome Society completed a questionnaire and submitted sufficient medical records to determine their otologic status. The majority (21/24) have had problematic otitis media (OM), and two thirds (16/24) have SNHL. In seven of the Turner subjects (age range: 12 to 51 years), gradual progressive SNHL began in late childhood or early adulthood. Molecular techniques showed no correlation between parental origin of the retained X chromosome and hearing status in 17 Turner subjects and at least one of their parents. SNHL and frequent OM appear to be independent variables that are both present in Turner syndrome. It is postulated that the presence of unpaired genes on the X chromosome may account for hearing loss and other phenotypic abnormalities seen in this syndrome.

In the US, approximately one in every 1000 children has hearing loss sufficiently severe to interfere with the acquisition of normal speech [Ann NY Acad Sci 630 (1991) 16]. The causes of non-syndromic hearing loss (NSHL) are known to be heterogeneous, with genetic factors accounting for 50-75%[Am J Med Genet 46 (1993) 486]. Often individuals with NSHL thought to be caused by mutations in GJB2 have only one detectable mutant allele [Am J Hum Genet 62 (1998) 792, Hum Mol Genet 6 (12) (1997) 2173]. Another gene that has been identified as a possible cause of NSHL is GJB6 that codes for the gap junction protein, connexin 30. A consecutive series of anonymous newborn dried blood specimens (n = 2089) was tested for two GJB2 mutations: (i) 35delG, a pan-ethnic mutation; and (ii) 167delT, a mutation more frequently found in individuals of Ashkenazi Jewish and Mediterranean descents. Mutation detection was validated using allele-specific oligonucleotide hybridization in single wells. Once the positive samples had been identified, the samples were pooled and retested. All positives in the individual experiment were correctly identified in the pooled experiment. The same random set of anonymous newborn dried blood specimens plus some additional samples were tested (n = 2112) for the 342-kb deletion in the GJB6 gene.

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Turner syndrome is one of the most common chromosomal aneuploidies, affecting girls only at a rate of 1 in 1000 births.1 Human beings have only one active X chromosome after early embryogenesis, the only X chromosome present in a male karyotype and one of the two X chromosomes present in a female karyotype. Inactivation of the second X in females is initiated through methylation of the X-activation center located on the long arm of the X chromosome (at Xq13). Although this inactivation is ordinarily random, selective nonrandom inactivation often occurs on X chromosomes that carry deleterious genes or that are structurally abnormal.Individuals with Turner syndrome are phenotypic females, but they have an abnormal karyotype in which one of the X chromosomes is either absent or is structurally abnormal from deletion or translocation. Generally, a structurally abnormal X chromosome is inactivated in individuals with Turner syndrome.Hearing loss has been well documented to be a feature of the syndrome, but the specific cause of sensorineural heating loss (SNHL) is unknown. Although both a high rate of otitis media and SNHL exist, elevated bone conduction thresholds do not appe~ to be a sequela of middle ear disease. 2 There is no radiographic evidence of otic capsule malformations, and the lesion is assumed to involve the membranous cochlea. 3 Could X-linked genes account for SNHL in this syndrome? No increased incidence of hearing loss is known in the brothers of girls with Turner syndrome, so a classic X-linked recessive type of inheritance is clearly not operative. However, the presence of paired gene alleles in at least the part of the Y chromosome that corresponds to such genes on the X chromosome implies that altered expression of X-chromosomal mutant genes when there is no second sex chromosome present, a gone dosage effect, may occur in Turner syndrome.