GJB2 mutation analysis was performed in 179 unrelated subjects with sporadic or familial hearing loss (HL). Among 57 families, 18 showed a vertical transmission of HL, the disease being present in two or three generations. Besides 155 nonsyndromic cases, 24 patients presenting with extra-auditory clinical signs were included in the molecular study. GJB2 mutation analysis was also performed in 19 subjects with an anamnestic history of perinatal risks factors for acquired HL. The 35delG mutation accounted for 22.1% of analyzed chromosomes in sporadic cases and 39.4% in familial cases; 35delG prevalence reached 41% in autosomal recessive and 44.4% in pseudodominant pedigrees. Two novel GJB2 mutations were identified in compound heterozygosity with 35delG allele (D159V, 284ins/dup[CACGT]). Two 35delG homozygous subjects were identified among HL cases classified as environmental in origin. Four patients 35delG heterozygous (35delG/V95M, 35delG/L90P, 35delG/167delT, and 35delG/?) and two homozygous presented with extra-auditory clinical signs involving different organs (skin, vascular system, hemopoietic lineages, and thyroid). In a high proportion of 35delG heterozygous HL patients (52%), no second GJB2 mutation was detected. The reported data highlight the complexity of the genetic epidemiology of GJB2-linked deafness, further enlarging the spectrum of situations in which GJB2 mutation analysis should be performed. The presence of extra-auditory signs in a significant portion of GJB2-mutated patients suggests the possibility that GJB2 loss of function could contribute to clinical phenotypes presenting in association with deafness. This hypothesis deserves further investigation. The failure to identify a presumed partnering GJB2 mutation in a high proportion of deaf patients remains a challenging problem to be clarified.

No abstract

We present the case of a 68 year-old man with a diffused hypertrophic pachymeningitis (HP) involving both internal auditory canals. The clinical symptoms were headache, decreased vision in one eye, progressive bilateral and symmetrical sensory-neural hearing loss (PSNHL) responsive to steroid treatment. Although hearing loss is a frequent manifestation of HP, only few studies reported an adequate audiological assessment and follow-up. Mechanisms related to the auditory involvement are discussed on the basis of audiological data. Gadolinium enhanced MRI is the most adequate technique for HP detection and for the differential diagnosis. A delay in the diagnosis of HP seems to be quite common and the consequences may be severe, especially in cases of optic nerve involvement. For these reasons, a cerebral MRI should probably be included in the assessment of PSNHL, especially when neurological signs coexist or are reported in the medical history.

Acute vertigo and sudden deafness in a patient with known cerebrovascular occlusive disease may represent the warning signs of an impending brain stem or cerebellar infarction, even when other neurologic signs are absent. These events are fortunately very rare, but should be considered by clinicians who see patients with vertigo.

In many world populations, mutations in the GJB2 gene (codifyng for Connexin 26) are the most common causes of autosomal recessive non-syndromic hearing loss and account for approximately 50% of cases. To date, more than 100 (dominant or recessive) mutations have been identified (The Connexin Deafness Homepage, 2009) and differences in frequency and distribution across the world are significant. In European and American Caucasian populations, the 35delG is the most common mutation found to account for nearly 70% of the pathological alleles. Mutations in the GJB6 gene (codifyng for Connexin 30) can co-occur in some cases (we refer to the 342-kb truncating deletion, named as GJB6-D13S1830)...... In accordance with the literature, all categories of HL were found. The severe-profound HL was predominant especially in T/T, T/NT forms. The 35delG is the most common mutation that we found, especially in profound hearing impairment. Mild-moderate HL was identified overall among NT/NT forms. Our findings confirm the importance of newborn screening, and the evaluation of genetic mutations to define genotype/phenotype correlation and clinical or audiological features useful to early diagnosis and improvement of therapeutic protocols