Townes-Brocks syndrome

Townes-Brocks syndrome (TBS), also known as renal-ear-anal-radial (REAR) syndrome, is a rare genetic disorder characterized by a triad of malformations affecting the ears, hands, and anorectal region. It is caused by pathogenic variants in the SALL1 gene on chromosome 16q12.1, which encodes a zinc finger transcription factor critical for embryonic development. The condition is present at birth and follows an autosomal dominant inheritance pattern, meaning a single copy of the altered gene is sufficient to cause the disorder. Approximately half of affected individuals have inherited the variant from a parent, while the remainder have a de novo (new) mutation. The hallmark features of Townes-Brocks syndrome include external ear anomalies (dysplastic, overfolded, or 'lop' ears, often with preauricular tags or pits), sensorineural and/or conductive hearing loss, thumb malformations (including preaxial polydactyly, triphalangeal thumbs, or hypoplastic thumbs), and imperforate anus or anal stenosis. Renal anomalies are also common and can range from mild structural abnormalities to severe renal hypoplasia or dysplasia, which may progress to end-stage renal disease. Other features that may occur include congenital heart defects (particularly ventricular septal defects and tetralogy of Fallot), foot malformations, and genitourinary anomalies. Intellectual disability is uncommon but has been reported in a minority of cases. There is no cure for Townes-Brocks syndrome, and management is directed at the specific symptoms present in each individual. Surgical correction of imperforate anus is typically required in the neonatal period. Hearing aids or cochlear implants may be needed for hearing loss. Renal function should be monitored throughout life, as progressive kidney disease can develop in childhood or adulthood, potentially requiring dialysis or kidney transplantation. Cardiac defects may require surgical intervention. Early diagnosis through clinical evaluation and molecular genetic testing of SALL1 allows for appropriate surveillance and timely management of complications.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Townes-Brocks syndrome