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--- townes_brock_syndrome [2026/06/15 15:56] – Scott Larson
+++ townes_brock_syndrome [2026/06/15 19:14] (current) – [Main Features] Scott Larson
@@ Line 1: / Line 1: @@
 ======Townes-Brocks Syndrome ======
-FIXME
 ====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====
-  * 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====
-  * [[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
-. Townes-Brocks Syndrome. National Library of Medicine (MedlinePlus).
-. 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.
-. 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.
-. SALL1-Related Townes-Brocks Syndrome. Graziano C, Olivucci G. GeneReviews® [Internet]. Updated 2025 Aug 14.
-. 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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syndrome