Townes–Brocks syndrome

Signs and symptoms

Individuals with Townes–Brocks syndrome may have abnormalities of the external ears, such as unusually large or small or misshapen ears, dysplastic ears, lop ear, or preauricular tags or pits. Hearing loss can be sensorineural or conductive. Anorectal malformations include imperforate anus, rectovaginal fistula, anal stenosis, or an unusually placed anus. Kidney abnormalities, sometimes leading to impaired function or failure, include hypoplastic, multicystic, or dysplastic kidneys.

Heart abnormalities such as tetralogy of Fallot and ventricular septal defects may occur. Hand and foot findings include hypoplastic thumbs, fingerlike thumbs, syndactyly, fusion of wrist bones, and overlapping foot or toe bones. Some children have learning difficulties, while others have normal intelligence. These prenatal abnormalities range from minor to severe, and most individuals have some but not all traits.

Causes

Townes–Brocks syndrome is an autosomal dominant condition caused by a mutation in the SALL1 gene, which encodes a transcriptional repressor that interacts with TRF1/PIN2 and localizes to pericentromeric heterochromatin. Its clinical features overlap with VATER and VACTERL associations, oculo-auriculo-vertebral spectrum, branchio-oto-renal syndrome, Fanconi anemia, and other anus-hand-ear syndromes. Although some symptoms can be life-threatening, many people with the syndrome live a normal lifespan.