**2.5 Brachio-Oto-renal (BOR) syndrome**

278 Hearing Loss

Pierre Robin sequence is usually a sporadic event with an estimated prevalence of about 1/10.000. In about 10% of patients a familial transmission has been described although the

**Hearing loss** is typically conductive and bilateral patients with Pierre Robin sequence. In Middle ear effusion is a finding in most patients. Therefore the use of tympanostomy (ventilation) tubes is the therapy of choice in patients with Pierre Robin Sequence. In a study by Handzic et al the mean hearing loss at speech frequencies was 24.5 dB (Handzić J et al., 1995, 1996). Pierre Robin Sequence is also a risk factor for sensorineural Hearing Loss: the 30% of the Pierre Robin patients in a study (Medard et al., 1999) had congenital permanent

Another study revealed multiple architectural anomalies involving the entire ear such as abnormal auricles or ossicles, aplasia of the lateral semicircular canals or a large vestibual

Stickler syndrome affects about 1 in every 7.500/9.000 newborns. Mutations in the *COL2A1, COL9A1, COL11A1*, and *COL11A2* genes impairing collagen production have been identified as the cause of this disorder. Except for *COL9A1* mutations which are transmitted in an autosomal recessive fashion, the syndrome is autosomal dominantly inherited. The affected patients show a typical long and flat face with malar and mandibular hypoplasia (midface hypoplasia). The nose is small with a depressed nasal bridge and anteverted nares. The flatness of the face gives the appearance of large eyes. Vision is altered: myopia, cataracts, glaucoma and retinal detachment can be some of the associated findings. Cleft palate, bifid

Joint problems are presented by the patients from an early age. This involves arthritis which causes joint pain and stiffness. Flattened vertebrae and spine deformity such as scoliosis or kyphosis vertebral may also be present. Additionally, the prevalence of mitral valve prolapse in this syndrome has been reported to be higher than that in the general

**Hearing loss** can be both sensorineural and conductive. The conductive hearing loss in Stickler syndrome type I (*COL2A1*) can be due to the stapedial fixation. It can therefore be

Mutations in the fibrillar collagen genes *COL11A1* and *COL11A2* can cause sensorineural hearing loss probably due to the essential role these two genes have in the function of the basilar or tectorial membranes. There seems to be a correlation of hearing loss severity, onset, progression and affected frequencies with the underlying mutated collagen gene (Shpargel et al, 2004). In the study by Admiraal et al the mean sensorineural hearing threshold in Stickler patients with *COL11A2* mutation was about 40 dB HL and was liable to

In the study conducted by Szymko-Bennett (Szymko-Bennett et al., 2001) most of the 46 adults with Stickler syndrome had a sensorineural hearing loss, affecting high frequencies. Additionally, hearing loss was not more progressive as compared to age-related hearing

involved genes have not been identified.

sensorineural evolutive hearing loss.

uvula and macroglossia may also occur.

improved by stapes surgery. (Baijens et al., 2004)

increase at the highest frequencies. (Admiraal et al., 2000)

aqueduct (Gruen et al., 2005).

**2.4 Stickler syndrome** 

population.

loss.

Branchio-oto-renal syndrome (OMIM 113650) is a genetic condition with a prevalence of 1/40.000 births and has an autosomal dominant mode of inheritance. *EYA1, SIX1*, and *SIX5* are three genes which are known to be mutated in this syndrome. The syndrome is called "Branchio-oto-renal" because malformations of the second branchial arch are associated with ears and renal abnormalities. The face is typically long and narrow with a constricted palate. (Alkis et al., 2002)Kidney and urinary tract show various degree of involvement. Shape or position abnormalities can be isolated or associated with an impaired renal function. Abnormalities in the development of the second branchial arch lead to neck malformations such as branchial cleft, cysts or fistulae.

**Auditory system** involvement ranges from pinnae abnormalities such as microtia, abnormally shaped ears, pre-auricular tags or pits to inner ear or middle ear malformations leading to sensorineural, conductive or mixed hearing loss. Hearing impairment occurs in 75%-93% of patients with BOR syndrome and ranges from mild to profound. Age of onset varies from early childhood to adult age. Younger patients manifest greater threshold fluctuation. Inner and middle ear anomalies ranges from cochlear hypoplasia, semicircular canals hypoplasia, ossicular anomalies, external auditory canal stenosis or atresia, vestibular displasia, enlarged aqueductus or endolymphatic sac (the last seems to predispose to more severe hearing impairment), absence of stapedium muscle or Eustachian tube dilation and cochlear nerve deficiency. (Huang et al., 2011; Kemperman et al., 2004)
