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townes_brock_syndrome [2026/06/15 16:46] – [Etiology] Scott Larsontownes_brock_syndrome [2026/06/15 19:14] (current) – [Main Features] Scott Larson
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 ======Townes-Brocks Syndrome ====== ======Townes-Brocks Syndrome ======
-FIXME+
 ====Main Features==== ====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==== ====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==== ====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==== ====Etiology====
   * Autosomal Dominant. Truncated SALL1 protein resulting from pathogenic variants acts in a dominant-negative fashion, disrupting organogenesis across multiple systems.   * Autosomal Dominant. Truncated SALL1 protein resulting from pathogenic variants acts in a dominant-negative fashion, disrupting organogenesis across multiple systems.
 ====Resources==== ====Resources====
-  * [[link|Title]] +  - [[https://medlineplus.gov/genetics/condition/townes-brocks-syndrome/|Townes-Brocks Syndrome. National Library of Medicine (MedlinePlus).]]   
-[Townes-Brocks syndrome](https://www.openevidence.com/rare-disease/townes-brocks-syndrome) (TBS) affects the eyes through a range of **structural and neurogenic ocular anomalies**, though these are considered rare features of the syndrome compared to the classic triad of anorectal, ear, and thumb malformations.[1][2] +  - [[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]] 
-**Structural Ocular Abnormalities** +  - [[https://www.ncbi.nlm.nih.gov/books/NBK1445/|SALL1-Related Townes-Brocks Syndrome. Graziano C, Olivucci G. GeneReviews® [Internet]. Updated 2025 Aug 14]]
- +
-The reported structural eye findings in TBS include:[3][2][4] +
- +
-- **Coloboma** — both iris coloboma and chorioretinal coloboma, the latter of which can cause significant vision loss +
-- **Microphthalmia** — abnormally small globe, reported rarely +
-- **Lamellar cataract** — congenital lens opacity +
-- **Epibulbar dermoid** — benign choristoma on the ocular surface +
-- **Optic nerve atrophy** +
-- **Retinal dystrophy** — described in at least one case report as a novel finding[2] +
- +
-**Cranial Nerve Dysinnervation Anomalies**+
  
-A distinctive category of ocular involvement in TBS relates to anomalous cranial nerve innervation:[3] 
  
-- **[Duane syndrome](https://www.openevidence.com/rare-disease/duane-retraction-syndrome) (type 1)** — limited abduction due to absence or hypoplasia of the abducens nerve (CN VI), confirmed on MRI in at least one genetically confirmed case 
-- **Möbius sequence** — facial diplegia from CN VII involvement 
-- **Marcus Gunn jaw winking** — aberrant trigeminal-oculomotor synkinesis 
-- **Gustatory lacrimation** (crocodile tears) — aberrant reinnervation of the lacrimal gland 
-- **Absent emotional tearing** 
  
-MRI in one well-documented case demonstrated bilateral absence of the abducens nerve and unilateral absence of the facial nerve, providing an anatomic basis for these dysinnervation patterns.[3] 
  
-**Pathophysiology** 
  
-These ocular findings are thought to arise from the role of the **SALL1** transcription factor in embryonic development. Truncated SALL1 protein resulting from pathogenic variants acts in a dominant-negative fashion, disrupting organogenesis across multiple systems.[2][1] Recent research has also implicated aberrant primary cilia function and Sonic Hedgehog (SHH) signaling as contributing mechanisms, which may help explain the overlap between TBS and ciliopathy phenotypes.[5] 
  
-**Clinical Implications** 
  
-GeneReviews recommends awareness of these ocular features in the evaluation of patients with confirmed or suspected TBS.[4] Given the variability of ocular involvement — even within the same family — ophthalmologic evaluation should be part of the multidisciplinary assessment of affected individuals. 
  
-Would you like to explore the recommended surveillance protocols and screening guidelines for patients with Townes-Brocks syndrome across all organ systems? 
  
-### References 
  
-1. Townes-Brocks Syndrome. National Library of Medicine (MedlinePlus). 
-2. 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. doi:10.1002/ajmg.a.62050. 
-3. 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. doi:10.1016/j.jaapos.2019.12.004. 
-4. SALL1-Related Townes-Brocks Syndrome. Graziano C, Olivucci G. GeneReviews® [Internet]. Updated 2025 Aug 14. 
-5. Truncated SALL1 Impedes Primary Cilia Function in Townes-Brocks Syndrome. Bozal-Basterra L, Martín-Ruíz I, Pirone L, et al. American Journal of Human Genetics. 2018;102(2):249-265. doi:10.1016/j.ajhg.2017.12.017. 
  
  
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