Otofaciocervical Syndrome 1

A number sign (#) is used with this entry because of evidence that otofaciocervical syndrome-1 (OTFCS1) is caused by a contiguous gene deletion involving the EYA1 gene (601653). One patient has been reported with a heterozygous mutation in the EYA1 gene.

Description

Otofaciocervical syndrome (OTFCS) is a rare disorder characterized by facial anomalies, cup-shaped low-set ears, preauricular fistulas, hearing loss, branchial defects, skeletal anomalies including vertebral defects, low-set clavicles, winged scapulae, sloping shoulders, and mild intellectual disability (summary by Pohl et al., 2013).

Genetic Heterogeneity of Otofaciocervical Syndrome

OTFCS2 (615560) is caused by mutation in the PAX1 gene (167411) on chromosome 20p11.

Clinical Features

Otofaciocervical syndrome was described by Fara et al. (1967) in a man and 4 of his 7 children. The otologic features were conductive hearing loss and prominent auricles with large conchae and preauricular fistulas just in front of the helix. Lateral cervical fistulas were present in some. Sunken nasal root, narrow nose, and long face were striking. The neck appeared long with sloping shoulders, low-set clavicles, and winged scapulae. All showed a mild intellectual deficit. Gorlin (1982) stated that this was the only known kindred with this disorder.

Dallapiccola and Mingarelli (1995) presented a sporadic case which they suggested supports the distinctness of the otofaciocervical syndrome. Distinguishing features were a long face with narrow nose, highly arched palate, prominent and dysmorphic ears, long neck, sloping shoulders and clavicles, winged, low and laterally set scapulae, tetralogy of Fallot, and deafness secondary to cochlea malformation. Several features present in the original family, including lateral cervical fistulae, had suggested that otofaciocervical syndrome is a variant of branchiootorenal syndrome (BOR; 113650). The absence of preauricular tags, lacrimal duct stenosis, and renal malformations, and the presence of distinct facial and radiographic findings and markedly downward sloping shoulders in their patient led Dallapiccola and Mingarelli (1995) to suggest that the syndrome is a unique, clinically recognizable entity.

Rickard et al. (2001) presented evidence that the otofaciocervical syndrome is a contiguous gene deletion syndrome involving the EYA1 gene, which is the site of mutations causing the branchiootorenal syndrome. One of the 2 patients they studied had previously been reported by Rajput et al. (1999). She presented with moderate hearing loss, bilateral preauricular pits, a single lacrimal duct, a cup-shaped ear, and unilateral facial palsy. A congenital cholesteatoma was identified in her right middle ear and was treated surgically. She was of short stature and had a short neck and pronounced sloping shoulders, with limited shoulder abduction. X-rays showed lateral displaced scapulae. She had mild developmental delay. A renal ultrasound showed a small left kidney and a right kidney of normal size with a bifid pelvis. Both parents were unaffected and intellectually normal.

Molecular Genetics

Estefania et al. (2006) described a patient with the OTFC syndrome who had a change of the first nucleotide in intron 6 of the EYA1 gene from guanine to adenine (540+1G-A; 601653.0014). The patient, who was 29 years old at the time of report, had bilateral conductive hearing loss and multiple malformations that led to the diagnosis of OTFC dysplasia. Chest x-ray showed diastasis of the right sternoclavicular joint, and urography demonstrated bilateral sponge kidneys. The patient had a long and narrow face, preauricular and cervical pits, prominent and cupped ears, a highly arched palate, sloping shoulders and clavicles, and trapezius hypoplasia which allowed adduction of the shoulders. Possibly unrelated to the syndrome, the patient had a selective deficiency of IgA.