Townes-Brocks Syndrome

• Autosomal Dominant. Truncated SALL1 protein resulting from pathogenic variants acts in a dominant-negative fashion, disrupting organogenesis across multiple systems.

• Title

[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]

Structural Ocular Abnormalities

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.