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It should be pointed out that in 70 percent of cases of hereditary deafness, there are no other somatic or neurologic abnormalities To date, three separate autosomal mutations have been identi ed that are associated with this pure nonsyndromic type of hereditary deafness, the most common of which is in the connexin gene as discussed in Chap 15 In one such family from Costa Rica, the gene codes for a protein that regulates the polymerization of actin, the major cytoskeletal component of the hair cells of the inner ear (see review by Pennisi) More recently, a number of mitochondrial disorders have been associated with deafness alone as well as with a number of the better-characterized mitochondrial syndromes (see Chap 37) The age of onset of hearing loss in the pure forms has been variable, extending well into adulthood.

Striae are extremely common, and develop between ages 5 and 50, although they predominate during growth periods such as puberty and pregnancy. There is a 25% to 35% overall incidence during puberty, and a 77% overall incidence during pregnancy.66 They are more common in younger women experiencing their rst pregnancy than in older pregnant women. Striae are more prevalent among Caucasians than other races, and occur twice as frequently in women as in men. They are also associated with conditions causing excess cortisol, such as Cushing syndrome.66

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Hereditary Hearing Loss with Retinal Diseases Konigsmark has separated this overall category into three subgroups: patients with typical retinitis pigmentosa, those with Leber optic atrophy, and those with other retinal changes With respect to retinitis pigmentosa, four syndromes are recognized in which retinitis pigmentosa appears in combination: with congenital hearing loss (Usher syndrome); with polyneuropathy (Refsum syndrome); with hypogonadism and obesity (Alstrom syndrome); and with dwar sm, mental retardation, premature senility, and photosensitive dermatitis (Cockayne syndrome) Hereditary hearing loss with optic atrophy forms the core of four special syndromes: dominant optic atrophy, ataxia, muscle wasting, and progressive hearing loss (Sylvester disease); recessive optic atrophy, polyneuropathy, and neural hearing loss (RosenbergChutorian syndrome); optic atrophy, hearing loss, and juvenile diabetes mellitus (Tunbridge-Paley syndrome); and opticocochleodentate degeneration with optic atrophy, hearing loss, quadriparesis, and mental retardation (Nyssen van Bogaert syndrome).

5:

motor neuron (SMN) site The SMN protein participates in forming protein-RNA complexes (so-called small nuclear ribonucleoproteins and RNA) that are essential for gene splicing Within the SMN locus there are two genes: SMN1, which generates a fulllength, fully functional form of SMN, and SMN2, which makes a truncated, partially functional SMN Making matters more complex, some individuals have more than two copies of SMN2 As a result, loss of both copies of SMN1 may cause very severe SMA in some individuals (in whom only one copy of SMN2 compensates for loss of SMN1), while others with multiple copies of SMN2 have milder disease Thus, the amount SMN1 and SMN2 protein determines the severity of disease Affected siblings demonstrate very similar clinical patterns of disease However, the same gene error gives rise to very different phenotypes in different families, so that modifying posttranscriptional or nongenetic attributes must be playing a role.

Hearing loss has also been observed with other retinal changes, two of which might be mentioned here: Norrie disease, with retinal malformation, hearing loss, and mental retardation (oculoacousticocerebral degeneration), and Small disease, with recessive hearing loss, mental retardation, narrowing of retinal vessels, and muscle atrophy In the former, the infant is born blind, with a white vascularized retinal mass behind a clear lens; later the lens and cornea become opaque The eyes are small and the iris is atrophied In the latter, the optic fundi show tortuosity of vessels, telangiectases, and retinal detachment The nature of the progressive generalized muscular weakness has not been ascertained Hereditary Hearing Loss with Diseases of the Nervous System There are several conditions in which hereditary deafness accompanies degenerative disease of the peripheral or central nervous.

Question 8-6

Less often, autosomal dominant and X-linked patterns of inheritance have been found, usually in adults Clinical Manifestations of Early-Onset Classic Werdnig-Hoffmann Type; SMA I The most frequent form of these spinal muscular atrophies, the severe infantile type, is a common disease, occurring once in every 20,000 live births After cystic brosis, it is the most frequent cause of death from a recessively inherited disease Characteristically the infant, usually born normally, is noted from birth to be unnaturally weak and limp ( oppy ) Some mothers report that fetal movement in utero had been less than expected or lacking altogether In severe cases, arthrogryposis at the ankles and wrists or dislocation of the hips is noted at birth (page 1244) The muscle weakness in these children is generalized from the beginning, and death comes early, usually within the rst year.

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