**2.10 Saethre-Chotzen syndrome**

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

#### **2.11 Townes-Brocks syndrome**

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

Renal and genitourinary abnormalities, congenital heart disease, foot malformation and mental retardation have also been described in Townes-Brocks syndrome.
