Townes-Brocks syndrome is characterized by three main features:

• Imperforate anus (84% of the cases)
• Abnormally shaped ears (87% of the cases)
• Thumb malformations (89% of the cases) such as triphalangeal thumbs (when a thumb has 3 bones instead of 2 bones), duplication of the thumb (two tumbs), and rarely, very small thumbs).

Most people with this condition have at least two of these three major features.

Other frequent findings include:

• Hearing problems
• Kidney problems (such as end-stage renal disease (ESRD), which may occur with or without kidney malformations (malrotation, abnormal position (ectopia), abnormal shape (horseshoe kidney), small size (renal hypoplasia), multiple cysts in the kidney (polycystic kidneys), or vesicoutereral reflux).
• Congenital heart disease
• Foot malformations (flat feet, overlapping toes)
• Genital or urinary malformations
• Intellectual disability.

Rare features include eye anomalies (a defect on the iris of the eye (iris coloboma), or an eye movement disorder known as Duane anomaly), Arnold-Chiari malformation type 1, and growth delay.

Townes-Brocks syndrome (TBS) is diagnosed when a patient has the following three major features:

• Imperforate anus
• Abnormally shaped ears
• Typical thumb malformations (two thumbs (preaxial polydactyly), triphalangeal thumbs which have three bones in them, much like the fingers, instead of the normal two, hypoplastic or underdeveloped thumbs) without shortening of the radius (the larger of the two bones in the forearm).

If only two major features are present, the presence of minor features and the absence of atypical features further support the diagnosis:

Minor features:

• Hearing impairment
• Foot malformations
• Kidney impairment with or without kidney malformations
• Genital or urinary malformations
• Congenital heart disease.

Atypical features (not suggestive of the syndrome):

• Radius hypoplasia on clinical examination or radiographs of the forearm
• Cleft lip/palate.

A genetic test identifying a mutation in the SALL1 gene establishes the diagnosis if clinical features are inconclusive. A few patients with clinical features of the syndrome have a mutation in the SALL4 gene. Therefore, people with a diagnosis of Townes-Brocks syndrome, who have a negative SALL1 testing, should also have a genetic testing for the SALL4 gene.

Treatment is directed towards the specific symptoms, including immediate surgical intervention for imperforate anus, surgery for severe malformations of the thumbs, and early treatment of hearing loss. When heart defects are present, treatment is with the routine management of congenital heart defects, such as surgery and medication; Kidney impairment is treated with hemodialysis and, in some cases, with kidney transplantation for end-stage renal disease (ESRD). Regular monitoring of kidney function in individuals, with and without kidney anomalies, is recommended. An annual hearing testing is recommended.