IMR Press / CEOG / Volume 48 / Issue 5 / DOI: 10.31083/j.ceog4805160
Open Access Letter to the Editor
Accuracy of facts about Freeman-Sheldon syndrome
Show Less
1 Craig R Dufresne, Fairfax, VA 22031, USA
2 Department of Surgery, Virginia Commonwealth University, Richmond, VA 23284, USA
*Correspondence: luikart2@gmail.com (Mikaela I Poling)
Clin. Exp. Obstet. Gynecol. 2021, 48(5), 997–998; https://doi.org/10.31083/j.ceog4805160
Submitted: 10 February 2021 | Revised: 24 February 2021 | Accepted: 25 February 2021 | Published: 15 October 2021
Copyright: © 2021 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).

Dear editor,

We read with great interest the article by Wróblewska-Seniuk, Jarząbek-Bielecka, and Kędzia titled, “Freeman-Sheldon syndrome - a course of the disease from birth to adulthood” [1]. The longitudinal history of a 25-year-old woman, reported as having Freeman-Sheldon syndrome [Freeman-Burian syndrome (FBS)] and undergoing labiaplasty for labia minora hypertrophy, is described [1, 2]. It is excellent to see this exquisitely rare syndrome discussed. Unfortunately, this article is somewhat unclear, and with omission of relevant recent literature, potentially harmful ideas are repeated, which this letter seeks to correct.

Without photographs or a detailed description of how the patient met the diagnostic criteria, it is not certain she had FBS. Stating the patient had FBS is insufficient, considering the false positive rate may be between 30–60% [3]. It is also unclear if the authors participated in the longitudinal care. If a retrospective records review was done, it should be stated. Medical records may be incomplete, and they lack intangible information.

In discussing clinical features of FBS, they list common features, including some from the diagnostic criteria [1, 3, 4, 5]. They do not, however, state the clinical diagnostic criteria [1, 3, 4, 5]. They place a great emphasis on distal extremity contractures, which are a non-diagnostic finding in FBS and common in many syndromic and non-syndromic entities [1, 3, 4, 5, 6]. Not directly stating the diagnostic criteria can confuse the reader unfamiliar with FBS.

While FBS has had many classifications since its first description in 1938 [7], it appears to be a complex congenital myopathic craniofacial syndrome, as arthrogrypotic findings are not pathognomonic [3, 6]. In the syndrome, “bone anomalies” are secondary effects of the primary myopathic process of fibrose tissue replacement of normal muscle fibers (not increased muscle tone) [1, 3, 8, 9]. This fibrose tissue acts as constricting bands, the way collagen behaves in severe burns [3, 8, 9]. This is correlated with in vitro molecular myophysiology observations showing problems with the metabolic process for contraction and extreme muscle stiffness that reduces muscular work and power [10, 11, 12]. Misunderstanding of etiology in FBS has led to inappropriate treatment plans, especially surgeries, and has resulted in tragic, lifelong impairments [3, 8, 9, 13].

Cases once believed to represent an autosomal recessive or X-linked inheritance pattern are now, based on new evidence, believed to be a germline mosaicism [8]. Most inherited cases are autosomal dominant, however [3, 8]. “Sporadic” refers to a trait not having been inherited and is not associated with “causes”. Both inherited (as autosomal dominant) and non-inherited (sporadic) cases have been shown to have MYH3 mutations [5]. Ultrasound for prenatal FBS diagnosis is very limited and not possible before 20 weeks [8]. No data on life-expectancy exist [3, 8].

Anesthesia in FBS is very difficult and poses many risks [14]. While a malignant hyperthermia (MH) event is always life-threatening, the potential association of MH and FBS was based on a single report of two cases, but non-MH hyperthermia may commonly occur in FBS patients [14].

Finally, the authors confuse “esthetic” for “reconstructive” surgery, mental retardation for developmental delay caused by physical anomalies, and problems “in the eyes” for “involving the eyes” [8, 9]. Nonetheless, this article adds to the discussion of FBS, while illustrating the perils of describing a rare condition.

Abbreviations

FBS, Freeman-Burian syndrome; MH, malignant hyperthermia.

Author contributions

MIP and CRD drafted the letter together. Both authors read and approved the final manuscript.

Ethics approval and consent to participate

Not applicable.

Acknowledgment

We thank CM Poling for critical review and proofreading and our families for their love and support. This manuscript is dedicated to the memory of Calvin Yang, formerly of the 2nd Battalion, 27th Infantry Regiment “Wolfhounds” of the US Army, who lost his life to complications of posttraumatic stress disorder several years after serving.

Funding

This research received no external funding.

Conflict of interest

The authors declare no conflict of interest.

References
[1]
Wróblewska-Seniuk K, Jarząbek-Bielecka G, Kędzia W. Freeman-Sheldon syndrome - a course of the disease from birth to adulthood. Clinical and Experimental Obstetrics and Gynecology. 2020; 47: 978–982.
[2]
Poling MI, Dufresne CR. Revisiting the many names of Freeman-Sheldon syndrome. Journal of Craniofacial Surgery. 2018; 29: 2176–2178.
[3]
Poling MI, Dufresne CR, Chamberlain RL. Findings, phenotypes, diagnostic accuracy, and treatment in Freeman-Burian syndrome. Journal of Craniofacial Surgery. 2020; 31: 1063–1069.
[4]
Stevenson DA, Carey JC, Palumbos J, Rutherford A, Dolcourt J, Bamshad MJ. Clinical characteristics and natural history of Freeman-Sheldon syndrome. Pediatrics. 2006; 117: 754–762.
[5]
Toydemir RM, Rutherford A, Whitby FG, Jorde LB, Carey JC, Bamshad MJ. Mutations in embryonic myosin heavy chain (MYH3) cause Freeman-Sheldon syndrome and Sheldon-Hall syndrome. Nature Genetics. 2006; 38: 561–565.
[6]
Poling MI, Dufresne CR. Head first, not feet first: Freeman-Sheldon syndrome as primarily a craniofacial condition. The Cleft Palate-Craniofacial Journal. 2018; 55: 787–788.
[7]
Freeman EA, Sheldon JH. Cranio-carpo-tarsal dystrophy: undescribed congenital malformation. Archives of Disease in Childhood. 1938; 13: 277–283.
[8]
Poling MI, Dufresne CR, Chamberlain RL. Freeman-Burian syndrome. Orphanet Journal of Rare Diseases. 2019; 14: 14.
[9]
Poling MI, Dufresne CR, Portillo AL. Identification and recent approaches for evaluation, operative counseling, and management in patients with Freeman-Burian syndrome: principles for global treatment. Journal of Craniofacial Surgery. 2019; 30: 2502–2508.
[10]
Racca AW, Beck AE, McMillin MJ, Korte FS, Bamshad MJ, Regnier M. The embryonic myosin R672C mutation that underlies Freeman-Sheldon syndrome impairs cross-bridge detachment and cycling in adult skeletal muscle. Human Molecular Genetics. 2015; 24: 3348–3358.
[11]
Walklate J, Vera C, Bloemink MJ, Geeves MA, Leinwand L. The most prevalent Freeman-Sheldon syndrome mutations in the embryonic myosin motor share functional defects. Journal of Biological Chemistry. 2016; 291: 10318–10331.
[12]
Bell KM, Kronert WA, Guo Y, Rao D, Huang A, Bernstein SI, et al. The muscle mechanical basis of Freeman-Sheldon syndrome. Biophysical Journal. 2016; 110: 14a.
[13]
Poling MI, Dufresne CR, McCormick RJ. Identification and recent approaches for evaluation and management of rehabilitation concerns for patients with Freeman-Burian syndrome: principles for global treatment. Journal of Pediatric Genetics. 2020; 9: 158–163.
[14]
Poling MI, Dufresne CR. Freeman-Burian syndrome. Anästh Intensivmed. 2019; 60: S8–S17.
Share
Back to top