Townes-Brocks Syndrome -CEW

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======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.
====Resources====
  - [[https://medlineplus.gov/genetics/condition/townes-brocks-syndrome/|Townes-Brocks Syndrome. National Library of Medicine (MedlinePlus).]]  
  - [[https://pubmed.ncbi.nlm.nih.gov/33438842/|Adult diagnosis of Townes–Brocks syndrome with renal failure: Two related cases and review of literature. Beaudoux O, Lebre AS, Doco Fenzy M, et al. American Journal of Medical Genetics. Part A. 2021;185(3):937-944]]
  - [[https://pubmed.ncbi.nlm.nih.gov/31981611/|Ocular Features of Townes-Brocks Syndrome. Valikodath NG, Jain S, Miller M, Kaufman LM. Journal of AAPOS : The Official Publication of the American Association for Pediatric Ophthalmology and Strabismus. 2020;24(2):115-118]]
  - [[https://www.ncbi.nlm.nih.gov/books/NBK1445/|SALL1-Related Townes-Brocks Syndrome. Graziano C, Olivucci G. GeneReviews® [Internet]. Updated 2025 Aug 14]]












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