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Syndromes Causing Sensory Loss

Alport Syndrome

In 1927, A. Cecil Alport first described a syndrome associated with hearing loss also marked by hematuria. The syndrome has a prevalence of 1 in 5000, with 85% of patients having the X-linked form. Non-congenital, sensorineural deafness very frequently, though not always, accompanies the nephropathy of Alport syndrome. The severity of renal disease varies with regard to the type of Alport syndrome and the sex of the individual. It should be noted that patients with this syndrome are also at increased risk for hypertension.

In addition to hearing impairment and renal disease, a variety of ocular lesions and defects are common in patients with Alport syndrome, including anterior lenticonus (congenital condition of the lens in which the surface is conical), progressive distortion of the lens, and pigmentary changes. In fact, the presence of anterior lenticonus is strongly suggestive of a diagnosis of Alport syndrome.

CHARGE Association

The CHARGE acronym stands for coloboma of the eye, heart abnormalities, (choanal) atresia, retardation of cognitive development, genital hypoplasia, and ear abnormalities/deafness. Its incidence is estimated at 1 in 12,000. The cause of CHARGE association is not known. Visual problems in persons with CHARGE Association are typically associated with eye abnormalities in the pupil, retina, or optic nerve. Individuals with CHARGE Association are often extraordinarily sensitive to light. Hearing loss can be conductive and/or sensorineural; and 80% of children with CHARGE Association experience some hearing impairment. Additional medical complications may include neonatal brainstem dysfunction with cranial nerve palsy and central nervous system and/or esophageal malformations.

Down Syndrome

Down syndrome is caused by a chromosomal abnormality (Trisomy 21) and is often associated with mental retardation, congenital heart disease, gastrointestinal abnormalities, respiratory difficulties, myopia, and other visual impairment. Hearing loss in individuals with Down syndrome can be sensorineural, conductive, or mixed type. Individuals with Down syndrome are at increased risk for early onset Alzheimer's disease, as well as leukemia and leukemoid reactions. The incidence of Down syndrome varies with maternal age; for example, incidence at maternal age 30 is 1 in 1,000, but incidence at maternal age 40 is 9 in 1,000.

Oculo-Auriculo-Vertebrali (OAV) Spectrum

This spectrum of disorders is also known as Goldenhar syndrome, or Hemifacial Microsoma, and is characterized by facial asymmetry, ocular findings, auricular abnormalities, and vertebral changes. About 50% of patients with OAV have some type of hearing impairment, and 5-15% of patients with OAV have some mild cognitive impairment. The cause of OAV is not known. Incidence is estimated at 1 per 45,000 to 55,000.

Marshall and Stickler Syndromes

Both Marshall and Stickler syndromes are dominantly inherited chrondrodysplasias. Both are marked by sensorineural hearing loss, high myopia, and midfacial hypoplasia. There is some debate among researchers as to whether or not Marshall and Stickler syndromes are indeed distinct, given the overlapping characteristics. Marshall syndrome is thought to be uniquely characterized by ectodermal abnormalities, orbital hypertelorism (excessive width between the eyes), and reduced sweat production. The incidence and prevalence of these syndromes are not known.

Rubella Syndrome

Adults and children who contract Rubella typically experience mild symptoms such as rash, fever, headache, malaise, and runny nose. The contagious viral infection poses greatest risk to the fetus in utero, particularly if the mother is infected during the first trimester. Medical and developmental complications associated with congenital Rubella include microcephaly, mental retardation, sensorineural hearing loss, cataracts, retinopathy, nystagmus, glaucoma, and optic atrophy and heart defects. In addition to medical and sensory difficulties, individuals with this syndrome may experience abnormal growth.

Usher Syndrome

Usher syndrome is, in fact, a group of syndromes, named for Charles Usher. All types of the syndrome are inherited as an autosomal recessive trait. The incidence of Usher syndrome is roughly estimated to be 1 in 20,000. Usher syndrome is responsible for six to ten percent of cases involving hereditary hearing loss and over fifty percent of all cases of deafblindness.

There are three discrete clinical categories of Usher syndrome: Type I, Type II, and Type III. The three categories are distinguished primarily by severity and age of onset of the various symptoms. Type I Usher syndrome is characterized by congenital severe to profound hearing impairment, progressive retinal degeneration beginning in childhood, and vestibular dysfunction. Type II Usher syndrome is characterized by moderate to severe hearing impairment, typical vestibular functioning, and a later onset of retinal degeneration. Type III Usher syndrome is the rarest form, and is characterized by progressive hearing impairment with variable retinal and vestibular symptoms.

Cytoskeletal abnormalities may be present, and research has suggested that individuals with the Usher syndromes are also at increased risk for psychosis. The results of imaging studies suggest a broad impact of the disease on the brain, not limited to auditory or visual systems.

Waardenburg Syndrome

Waardenburg syndrome (also called Waardenburg syndrome type I) is inherited as an autosomal dominant trait, and is characterized by a wide nasal bridge, lateral displacement of the inner canthus of the eyes, pigmentary abnormalities, and cochlear deafness. Additional features of the syndrome may include dysmorphic facial and ocular features, hypopigmentation, and axial and limb skeletal abnormalities. Both spina bifida and Hirschsprung disease (aganglionic megacolon) may be more common in individuals with Waardenburg syndrome. A variation on Waardenburg syndrome, known as Klein-Waardenburg syndrome or Waardenburg syndrome type III, is characterized by deafness, blue eyes, musculoskeletal abnormalities, and fused joints in the arms. Waardenburg-Shah syndrome is called Waardenburg syndrome type IV. Incidence of the Waardenburg syndromes is estimated at 1 in 30,000. Nearly 90% of individuals with Waardenburg syndrome have a parent exhibiting symptoms of Waardenburg syndrome.


References

Blake, K.D., Russell-Eggitt, I.M., Morgan, D.W., Ratcliffe, J.M., & Wyse, R.K.H. (1990). Who's in CHARGE? Multidisciplinary management of patients with CHARGE assocation. Arch. Dis. Child, 65, 217-223.

Colville, D.J., & Savige, J. (1997). Ocular manifestations of autosomal recessive Alport syndrome. Opthalmic Genetics, 18, 161-173.

Goldenring, J. (2005). Rubella [Medline Plus Medical Encyclopedia entry]. Retrieved December 21, 2005 from http://www.nlm.nih.gov/medlineplus/ency/article/001574.htm.

Källen, K., Robert, E., Mastroiacovo, P., Castilla, E.E., & Källen, B. (1999). CHARGE Association in newborns: A registry-based study. Teratology, 60(6), 334-343.

Kashtan, C.E. (1999). Alport syndrome: An inherited disorder of renal, ocular, and cochlear basement membranes [Review]. Medicine, 78, 338-360.

Petit, C. (2001). Usher syndrome: From genetics to pathogenesis. Annu. Rev. Genomics Hum. Geneti., 2, 271-297.

Schaefer, G.B., Bodensteiner, J.B., Thompson, J.N., Kimberling, W.J., and Craft, J.M. (1998). Volumetric neuroimaging in Usher syndrome: Evidence of global involvement. American Journal of Medical Genetics, 79(1), 1-4.

Sondheimer, N. (2005). Waardenburg syndrome [Review in Medline Plus Medical Encyclopedia]. Retrieved December 22, 2005, from http://www.nlm.nih.gov/medlineplus/ency/article/001428.htm