Townes-Brocks syndrome is a rare multiple malformation syndrome characterized by anal, limb, ear, and renal anomalies. Intelligence is normal in most affected individuals. Diagnostic features include ano-rectal abnorma-lities (imperforate or anteriorly placed anus, anal stenosis, prominent midline perineal raphe); abnormalities of the hands and feet (preaxial polydactyly, triphalangeal thumbs, bifid thumbs and toes, finger and toe syndactyly); external ear malformations (preauricular tags or pits, “lop” or “satyr” ear, microtia, abnormal helix) with hearing loss (sensorineural, conductive or mixed); and renal anomalies leading to impaired renal function or renal failure (unilateral or bilateral hypoplastic or dysplastic kidneys, multicystic kidneys, renal agenesis, posterior urethral valves, vesicouretal reflex). Other, less common features are cardiac defects, mental retardation, eye, genitourinary and vertebral abnormalities, hypothyroidism, umbilical hernia, and gastroesophageal reflux. The intra- and interfamilial clinical presentation of TBS varies widely and overlaps with several other disorders including VATER and VACTERL associations, Okihiro syndrome, Fanconi anemia, Baller-Gerold syndrome, branchio-oto-renal (BOR) syndrome and oculo-auriculo-vertebral (OAV) spectrum. Important differentiating characteristics of TBS are the absence of radial hypoplasia, craniosynostosis, and tracheo-esophageal fistula. Prenatal full gene sequence analysis is available when fetal ultrasound abnormalities are suggestive of TBS.