**2.12 Miller syndrome**

282 Hearing Loss

Otologic malformations and **hearing loss** are common features in Pfeiffer syndrome. They are mainly due to external auditory canal or middle ear malformation. For example atresic or stenotic auditory canal, hypoplasic ossicules or fixed ossicular chain, hypoplasic or enlarged middle ear cavity can be common findings. The inner ear is usually normal though

In a study by Vallino et al. hearing loss, mostly moderate to severe, was present in eight of the nine patients with Pfeiffer syndrome. Seven patients had conductive hearing loss and

Sensorineural hearing loss is less common and may be related to the effect of *FGFR*

This is a genetic condition with an incidence which ranges from 1:25.000 to 1:50.000 births (OMIM 101400). It is inherited in an autosomal dominant way and it is caused by mutation of *TWIST1*. Patients with Saethre-Chotzen syndrome typically show an abnormal fusion in the skull's bones causing the typical appearance: brachycephaly, low frontal hair line, flattened nasofrontal angle with a beaked nose, widely spaced eyes, ptosis, facial asymmetry. Fingers and Toes defects such as mild syndactyly and a broad or duplicated thumb or hallux are typical; vertebral anomalies and short stature can also be associated.

Mild external ear anomalies can be additional findings. The hearing defect is usually conductive (Clauser et al., 2004) and can be due to stapes ankylosis, fixed ossicular chain, microtia or enlarged vestibules (sometimes associated to a small epitympanum and small or even absent mastoids) (Ensink et al., 1996). Mixed hearing loss due to brain stem anomalies

Townes-Brocks syndrome (OMIM 107480) is a genetic condition showing an incidence of about 1 in 250.000 live births. It is caused by mutations in *SALL1* causing abnormal production of transcription factors. It is inherited in an autosomal dominant pattern. Patients with this syndrome typically show the triad: anus imperforatus (in about the 82% of the patients) with rectovaginal or rectoperineal fistula, external ear anomalies (85%) usually associated with thumbs malformation (89%) such as thumb duplication or hypoplasia.

In 65%of cases sensorineural or conductive hearing loss are part of the clinical presentation. External ear anomalies range from overfolded superior helices which cause the typical satyr form, to microtia, preauricolar tags or pits and can be associated to middle ear anomalies (e.g. ossicular abnormalities, hypoplastic malleus head and abnormally shaped oval window andincus. (Toriello et al., 2004; Powell et al., 1999). The hearing loss is predominantly sensorineural and slowly progressive (from mild during early childhood to moderate in early adulthood), it affects high-frequency thresholds more than the low-frequency ones and

Renal and genitourinary abnormalities, congenital heart disease, foot malformation and

has a variable, but usually small, conductive component. (Rossmiller et al., 1994)

mental retardation have also been described in Townes-Brocks syndrome.

an enlarged internal acoustic meatus may be present. (Cremers et al., 1981)

mutations on cranial nerve or inner-ear development. (Desai et al., 2010)

one had mixed loss (Vallino-Napoli et al., 1996).

has also been described (Lamonica et al., 2010).

**2.11 Townes-Brocks syndrome** 

**2.10 Saethre-Chotzen syndrome** 

Miller syndrome or postaxial acrofacial dysostosis (OMIM 263750) is a rare condition which affects fewer than 1 in 1 million of newborns. It has an autosomal recessive mode of inheritance. Mutations in *DHODH* cause this syndrome disrupting the development of the first and second pharyngeal arch. Patients with this syndrome typically show craniofacial abnormalities such as malar hypoplasia, micrognathia, down-slanting eyes with drooping of the lower eyelids (which becomes more evident with age) and coloboma, cleft palate, long philtrum and small, protruding "cup-shaped" ears.

Craniofacial abnormalities are associated with limb defects such as syndactyly, hypoplasia or absence of fingers or toes (eg the fifth digits), hypoplasia of forearms or lower legs.

Extra nipples, vertebrae or ribs deformities have been described while abnormalities of the heart, kidneys, genitalia, or gastrointestinal tract are less common.

**Hearing loss** is usually caused by defects in the middle ear (various degree conductive hearing loss). (Toriello et al., 2004)
