Purpose
Timothy syndrome (TS) is characterized by congenital long-QT arrhythmia and limb syndactyly.
Patients who undergo syndactyly repair with undiagnosed TS may have their abnormal
cardiac electrical activity unmasked during surgery. The purpose of this study was
to detail the extremity phenotype seen in patients with TS, which may help hand surgeons
in their preoperative assessment.
Methods
This was a retrospective review of all patients with TS seen at our institution from
1998 to 2022. Descriptive statistics regarding their demographics, medical and surgical
histories, and syndactyly phenotypes were obtained.
Results
Seven patients (5 males and 2 females) with TS were seen at our institution for multidisciplinary
evaluation (median age at presentation was 23 months). Six patients had finger syndactyly
and 5 had toe syndactyly. One patient did not have any extremity syndactyly and was
noted to have a specific TS mutation known to lack musculoskeletal abnormalities.
All patients with finger syndactyly had border digit involvement, with 5 out of 6
patients displaying syndactyly of the middle-ring and ring-little finger web spaces.
Toe syndactyly was more heterogeneous, with 1 patient lacking any lower extremity
syndactyly and others having variable involvement of the second-third, third-fourth,
and fourth-little toe web spaces. Complexity ranged from simple to complete. Four
patients had intraoperative cardiac events leading to TS diagnoses after surgery.
Conclusions
Bilateral border digit hand syndactyly, with or without bilateral toe syndactyly,
should raise concerns for TS and prompt further investigation into potential cardiac
disease to avoid perioperative cardiac morbidity and mortality.
Type of study/level of evidence
Therapeutic V.
Key words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of Hand SurgeryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism.Cell. 2004; 119: 19-31
- Update on the molecular genetics of Timothy Syndrome.Front Pediatr. 2021; 9668546
- The heart-hand syndrome. A new variant of disorders of heart conduction and syndactylia including osseous changes in hands and feet.Kinderarztl Prax. 1992; 60: 54-56
- Timothy syndrome: a life-threatening syndactyly association: a case report.JBJS Case Connect. 2014; 4: e48
- Sudden cardiac arrest during anesthesia in a 30-month-old boy with syndactyly: a case of genetically proven Timothy syndrome.J Korean Med Sci. 2013; 28: 788-791
- Preoperative electrocardiograms for nonsyndromic children with hand syndactyly.J Hand Surg Am. 2015; 40: 452-455
- Novel gain-of-function variant in CACNA1C associated with Timothy syndrome, multiple accessory pathways, and noncompaction cardiomyopathy.Circ Genom Precis Med. 2020; 13e003123
- CACNA1C-related disorders.in: Adam M.P. Everman D.B. Mirzaa G.M. Pagon R.A. Wallace S.E. Bean L.J.H. Gripp K.W. Amemiya A. GeneReviews [Internet]. University of Washington, Seattle; Seattle (WA), February 11 2021: 910-916
- Severe arrhythmia disorder caused by cardiac L-type calcium channel mutations.Proc Natl Acad Sci U S A. 2005; 102: 8089-8096
- Anesthesia for patients with congenital long QT syndrome.Anesthesiology. 2005; 102: 204-210
- Clinical outcomes and modes of death in Timothy syndrome: a multicenter international study of a rare disorder.JACC Clin Electrophysiol. 2018; 4: 459-466
- A multicentre study of patients with Timothy syndrome.Europace. 2018; 20: 377-385
Article info
Publication history
Published online: November 03, 2022
Accepted:
September 12,
2022
Received:
June 4,
2022
Publication stage
In Press Corrected ProofFootnotes
No benefits in any form have been received or will be received related directly or indirectly to the subject of this article.
Identification
Copyright
© 2022 by the American Society for Surgery of the Hand. All rights reserved.
