Townes-Brocks Syndrome
Main Features
- Classic Triad
- Anorectal malformations
- imperforate anus, anal stenosis, anteriorly placed anus
- Dysplastic ears
- Sensineural and/or conductive hearing loss (65%)
- overfolded superior helices
- Preauricular skin tags
- Microtia
- Thumb malformations
- preaxial polydactyly
- triphalangeal thumbs
- hypoplastic thumbs (rare)
- without radial hypoplasia
Eye Findings
Cranial Nerve Dysinnervation Anomalies
- Duane syndrome(type 1)
- Möbius sequence
- Marcus Gunn jaw winking
- Gustatory lacrimation (crocodile tears) — aberrant reinnervation of the lacrimal gland
- Absent emotional tearing
Other ocular findings
- Coloboma — both iris coloboma and chorioretinal coloboma
- Microphthalmia — rare
- Lamellar cataract
- Epibulbar dermoid — benign choristoma on the ocular surface
- Optic nerve atrophy
- Retinal dystrophy — described in at least one case report as a novel finding
Other Findings
- More common
- Renal disease (30-40%)
- Hypoplasia, polycystic kidneys, horseshoe kidney, ectopia, unilateral agenesis
- End-stage kidney disease in adulthood
- Focal and segmental glomerulosclerosis
- Congenital heart disease (15%)
- More common in p.Arg276Ter variant
- ASD, VSC, tetralogy of Fallot, truncus arteriosus, pulmonary valve atresia, PDA
- GU malformations
- hypospadias, cryptorchidism, bifud scrotum, vaginal aplasia with bifud uterus
- Foot malformations
- flat feet, clubfoot, overlapping toes, syndactyly, missings toes (usually 3rd), hammer toes
- Chronic constipation, GI reflux
- Less Common
- Skeletal — rib anomalies (fused, missing, or cervical ribs), mild vertebral anomalies (~9%), painful joints in adults
- CNS — Chiari I malformation, cranial nerve palsies (CN VI, VII), hypoplasia of the corpus callosum
- Developmental/behavioral — developmental delay and learning difficulties in ~15%; ADHD in some children; adults typically do not have significant intellectual disability
- Endocrine — congenital hypothyroidism, growth hormone deficiency (rare)
- Other — hemifacial microsomia, postnatal growth deficiency (6–29% reported)
Etiology
- Autosomal Dominant. Truncated SALL1 protein resulting from pathogenic variants acts in a dominant-negative fashion, disrupting organogenesis across multiple systems.