Freeman-Sheldon, syndrome

[MIM 193 700, 277 720]

(Whistling face syndrome,  Whistler syndrome, the face of Whistler syndrome, cranio-carpo-tarsal syndrome, Freman-Burian syndrome, distal arthrogryposis type DA2A, Windmill-Vane-Hard syndrome) 

Not to be mistaken for Sheldon-Hall syndrome (see this term) [MIM 618436] or distal arthrogryposis type DA2B, also caused by a mutation of the MYH3 gene.

Prevalence is estimated at less than 1/106. Dysmorphic syndrome. Autosomal dominant and sometimes recessive [MIM 193 700] transmission  but most cases are sporadic. Mutation of the MYH3 gene (17p13.1) coding for one of the heavy chains of the embryonic myosin: this myosin is an essential element of the fetal myotubes and disappears progressively after birth. It is a slowly progressive myopathy with a congenital disproportion of the different types of muscle fibers (distal type DA2A arthrogryposis) involving especially the face, limbs, and respiratory muscles. Whitish fibrous bands replacing the damaged muscle are present in between normal muscle tissue.

A similar phenotype called CLIFAHDD, acronym for  Congenital contractures of the LImbs and FAce, Hypotonia, and Developmental Delay, caused by a mutation of the NALCN gene (13q33) [MIM 616 266]  is associated with developmental retardation.

The severity of the clinical presentation is variable.

Association of:

-        dysmorphism: elongated and poorly mobile facies, pursed lips as for whistling, microstomia, protruding nasolabial fold, 'H' or 'V' dimple on the chin, blepharophimosis, hypoplatic alae nasi, high-arched palate, long philtrum, sometimes mandibular and midface hypoplasia; sometimes scaphocephaly.

-        osseous anomalies and joint contractures: equinovarus clubfoot, campodactyly with ulnar deviation of the fingers

-        severe scoliosis, cyphosis, lordosis, reduced neck mobilityk

-        intercostal muscles are sometimes inefficient causing a restrictive syndrome with abdominal breathing and a risk of chronic cor pulmonale



Anesthetic implications: 

difficult intubation  because the opening of mouth is small and neck is often stiff. Difficult peripheral venous access . Stiffness during the administration of halothane or succinylcholine but children were anesthetized with halogenated agents without signs of malignant hyperthermia: the risk of developping an malignant hyperthermia is similar to that of the general population. Increased risk of postoperative respiratory complications. A febrile infant presented a malignant syndrome to neuroleptics following administration of multiple doses of metoclopramide.


References : 

-        Laishley RS, Roy WL.
Freeman-Sheldon syndrome: report of three cases and the anaesthetic implications.
Can Anaesth Soc J 1986; 33: 388-93.

-        Duggar RG, DeMars PD, Bolton VE.
Whistling face syndrome: general anesthesia and early postoperative caudal analgesia.
Anesthesiology 1989; 70: 545-7.

-        Jones R, Dolcourt JL.
Muscle rigidity following halothane anesthesia in two patients with Freeman-Sheldon syndrome.
Anesthesiology 1992; 77: 599-600

-        Sobrado CG, Ribera M, Mati M et al.
Freeman-Sheldon syndrome : generalized muscular rigidity after anesthetic induction.
Rev Esp Anestesiol Reanim 1994; 41: 182-4.

-        Munro HM, Butler PJ, Washington EJ.
Freeman-Sheldon (whistling face) syndrome. Anaesthetic and airway management.
Paediatr Anaesth 1997; 7: 345-8.

-        Robinson PJ.
Freeman-Sheldon syndrome: severe upper airway obstruction requiring neonatal tracheostomy.
Pediatr Pulmonol 1997; 23: 457-9.

-        Vas L, Naregal P.
Anaesthetic management of a patient with Freeman-Sheldon syndrome.
Paediatr Anaesth 1998; 8: 175-7.

-        Cruickshanks GF, Brown S, Chitayat D.
Anesthesia for freeman-Sheldon syndrome using a laryngeal mask airway.
Can J Anesth 1999; 46: 783-7

-        Agritmis A, Unlusoy O, Karaca S.
Anesthetic management of a patient with Freeman-Sheldon syndrome.
Pediatr Anesth 2004; 14: 874-7.

-        Kim JS, Park SY, Min SK, Kim JH, Lee SY, Moon BK.
Awake nasotracheal intubation using fiberoptic bronchoscope in a pediatric patient with Freeman-Sheldon syndrome.
Pediatr Anesth 2005; 15: 790-2.

-        Stein M, Sorscher M, Stanley C.
Neuroleptic malignant syndrome induced by metoclopramide in an infant with Freeman-Sheldon syndrome.
Anesth Analg 2006; 103: 786-7

-        Arora MK, Nagaraj G, Lakhe ST.
Combined spinal-epidural anesthesia for a child with Freeman-Sheldon syndrome with difficult airway.
Anesth Analg 2006; 103: 1624

-        Madi-Jebara S, El-Hajj C, Jawish D, Ayoub E, Kharrat K, Antakly M-C.
Anesthetic management of a patient with Freeman-Sheldon syndrome: a case report.
J Clin Anesth 2007; 19: 460-2

-        Richa FC, Yazbeck PH.
Anaesthetic management of a child with Freeman-Sheldon syndrome undergoing spinal surgery.
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-        Stevenson DE, Carey JC, Palumbos J, Rutherford A, Dolcourt J, Bamshad MJ.
Clinical characteristics and natural history of Freeman-Sheldon syndrome.
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-        Fisher K, Qasem F, Armstrong P, McConachie I.
Anesthetic considerations in a parturient with Freeman-Sheldon syndrome.
Int J Obstetr Anesth 2016; 81-4

-        Viehmeyer S, Gabriel P, Bauer S, Sodian R et al.
Case report anesthetic considerations for an adult patient with Freeman-Sheldon syndrome undergoing open heart surgery.
Case Rep Anesthesiol  2018  doi.org/10.1155/2018/78623278

-        Hamilton T, Sathyamoorthy MA.
Case of Freeman-Shedon syndrome: anesthetic challenges.
J Miss State Med Assoc 2016; 57: 6-8.

-        Fiorelli S, Leopizzi G, Massullo D, DAndrilli A, Ciccone AM, Rocco M.
Anesthetic management of a patient with Freeman-Sheldon syndrome in thoracic surgery.
J Clin Anesth 2018; 48: 48-9. 

-        Viehmeyer S, Gabriel P, Bauer K, Bauer S, Sodian R, Hilberath JN.
Anesthetic considerations for an adult patient wth Freeman-Sheldon syndrome undergoing open heart surgery.
Case Reports Anesthesiology 2018 doi 101155/2018/7862327.

-        Poling MI, Dufresne CR, Chamberlain RL.
Freeman-Burian syndrome.
Orphanet J Rare Dis 2019 ; 14, doi https://doi.org/10.1186/s13023-018-0984-2


Updated: March 2022