View/Download PDF
doi: 10.4103/jmsr.jmsr_126_19

Before scoliosis surgery look at the eyes and face of the child

Mustafa A Salih
 Division of Pediatric Neurology, College of Medicine, King Saud University, Riyadh, Saudi Arabia

Corresponding Author:
Mustafa A Salih
Division of Pediatric Neurology, College of Medicine, King Saud University, Riyadh
Saudi Arabia
How to cite this article:
Salih MA. Before scoliosis surgery look at the eyes and face of the child. J Musculoskelet Surg Res 2020;4:63-65
Copyright: (C)2020 Journal of Musculoskeletal Surgery and Research

Scoliosis in children, defined as lateral curvature and rotation of the vertebrae, can be congenital, syndrome-related, idiopathic, neuromuscular, or due to secondary causes.[1] Diagnostic workup is based on patient history, physical examination, and imaging, whereas the management is based on the age of the patient, nature of the curve, and risk of progression.[2]

Neuromuscular scoliosis (NMS), which is usually identified in early childhood, constitutes the second-most prevalent spinal deformity after idiopathic scoliosis.[3] Compared with idiopathic scoliosis, conservative and surgical treatment of NMS is more complex and has a higher complication rate.[4] This is because of the associated medical comorbidities and the presence of deformed spinopelvic anatomy.[5]

NMS is classified as neuropathic and myopathic types. Neuropathic type can be due to upper motor neuron lesions (e.g., cerebral palsy, spinal cord trauma, and syringomyelia), or diseases of the lower motor unit,[6] including the anterior horn cells (e.g., poliomyelitis and spinal muscular atrophy)[7] and the peripheral nerves.[8] Myopathic types include arthrogryposis multiplex congenita, muscular dystrophy, and other forms of myopathy.[9]

Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies inherited as autosomal recessive, usually starts in early childhood and have more severe progression compared to the autosomal-dominant varieties.[10] They are more common in the Arabian Peninsula and North Africa due to the high rate of consanguinity. Apart from the progressive weakness of the distal muscles in the feet and hands, some of them have associated facial weakness, which helps in recognizing the clinical entity. Scoliosis is a prominent feature in three of these, namely Charcot-Marie-Tooth disease type 4B1 (CMT4B1), Charcot-Marie-Tooth disease type 4C (CMT4C), and Charcot-Marie-Tooth disease type 4E (CMT4E).

The causative gene of CMT4B1 (the first identified autosomal recessive CMT gene) was found in the families of Italian and Saudi Arabian ancestries.[11],[12],[13] The disease usually starts before the age of 4 years with progressive distal weakness leading to pes cavus foot deformity, followed by proximal weakness of the lower limbs, and death may occur as early as the end of the second decade.[14] Facial and vocal cord pareses are known to be associated together with chest deformities and diaphragmatic weakness. Hence, special precautions need to be assured when performing surgery in these patients.

CMT4C is characterized by a relatively mild childhood or adolescent-onset demyelinating sensorimotor neuropathy associated with early-onset, severe, and rapidly progressing scoliosis. Other known associations include facial weakness, cranial nerve involvement, and deafness.[15]

CMT4E presents with neonatal hypotonia and delayed motor development accompanied by distal limb muscle weakness and atrophy due to a hypomyelinating form of peripheral neuropathy. Other features of the disease include facial weakness and cranial nerve involvement, scoliosis, and respiratory insufficiency due to neuropathy. The disease is caused by homozygous mutation in the EGR2 gene.[16]

Myopathic types of NMS associated with facial weakness include Ullrich congenital muscular dystrophy caused by mutations in the genes encoding collagen VI. The presence of round face with mild weakness and prominent ears are known features of the disease together with neonatal hypotonia, torticollis, kyphosis of the spine, hip dislocation, proximal joint contractures, and distal joint hyperlaxity.[9]

Congenital myasthenic syndromes (CMS) are heterogeneous disorders caused by impaired neuromuscular transmission resulting from genetic mutations of neuromuscular junction molecules. Currently, mutations in more than thirty genes were identified, causing autosomal dominant or autosomal recessive CMS. The autosomal recessive forms are more common in the Arabian Peninsula and North Africa. One of the first identified families with ALG2 gene mutation was from Saudi Arabia,[17] and the second identified family with MUSC mutation was from Sudan.[18]

Symptoms of CMS may present in utero with reduced fetal movements. Mutations in the AChR delta subunit or RAPSN may present at birth with arthrogryposis multiplex congenita.[19] Childhood manifestations of CMS include fatigable ptosis and extraocular muscle weakness (ophthalmoparesis), associated with bilateral facial weakness with tenting of lips.

According to the location of genetic dysfunction, symptoms, therapy, and contraindicated drugs vary in CMS. Symptoms of CMS caused by a mutation in the COLQ gene worsen after the use of acetylcholinesterase inhibitors, as documented in a large cohort, including Saudi patients.[20] Prominent scoliosis requiring surgery is a known complication of COLQ gene mutations.[21] Other causative aberrant genes of CMS associated with scoliosis include the VAMP1 gene, which encodes for a presynaptic protein and CHRNE gene encoding for the epsilon subunit of the acetylcholine receptor.[22] Patients with CHRNE gene mutations have been reported from Saudi Arabia,[23] and a common founder mutation c. 1293insG has been identified in North African populations.[24] Anesthetic management of CMS should be designed guided by each genotype to avoid drugs that could worsen or trigger the symptoms of CMS, and judicious respiratory care is required after the surgery.[25]

Another disorder in which progressive scoliosis is associated with ocular findings is horizontal gaze palsy with progressive scoliosis (HGPPS) characterized by the lack of voluntary horizontal eye movements and progressive scoliosis developing in childhood, often requiring surgical intervention early in life. The defective gene (inherited as autosomal recessive) was first mapped to chromosome 11q23-q25 in patients from Saudi Arabia (two Saudi and Indian families).[26] Mutations in the ROBO gene were later identified to be causative,[27] and lead to noncrossing of selected axonal paths in the central nervous system.[28]

Progressive scoliosis is a known complication of two diseases characterized by myotonia associated with facial and eye abnormalities. These are myotonic dystrophy type 1 (DM1), abbreviated DM1, and previously known as Steinert's disease, and Schwartz–Jampel syndrome.[9] DM1 is caused by a heterozygous dominant expansion of a set of CTG trinucleotide repeats, which may manifest in childhood with diffuse facial weakness, associated with tenting of the upper lip, difficulty smiling, and ptosis. Complications include pulmonary impairments such as decreased forced vital capacity and cardiac conduction disturbances, which need to be observed during scoliosis surgery.[29]

Schwartz–Jampel syndrome is a rare myotonic syndrome with osteoarticular deformities, inherited as autosomal recessive and is more frequent in the Arabian Peninsula and North Africa.[30],[31] Patients present with generalized myotonia, muscular hypertrophy, and osteochondrodysplasia. They have mask-like facies, microstomia, and blepharophimosis (narrow palpebral fissures). Caution should be taken during surgery to avoid suxamethonium and volatile anesthetic agents since the risk of the development of malignant hyperpyrexia and hyperkalemia has been reported.[32],[33]

Patients with myopathies caused by RYR1 gene mutations are at the risk of developing malignant hyperthermia during scoliosis surgery if they were exposed to the volatile inhalational anesthetic agents and the muscle relaxant succinylcholine.[34] They can manifest as minicore myopathy with external ophthalmoplegia (OMIM #255320),[35] a recessively inherited disease characterized by muscle weakness, amyotrophy, the involvement of extraocular muscles, ptosis, and other variable features including facial diplegia, scoliosis, kyphosis, and joint contractures.[36]

Another minicore-like myopathy, which can manifest with scoliosis, ptosis, and facial weakness, is Salih myopathy (OMIM # 611705), a recessively inherited disease described in consanguineous families of Arab descent, and caused by homozygous or compound heterozygous mutation in the gene encoding titin.[37] Titin is a giant muscle protein expressed in the cardiac and skeletal muscles. Patients with Salih myopathy are known to have cardiac septal defects and develop progressive dilated cardiomyopathy with rhythm disturbances. Cardiac surveillance is required beginning at the age of 5 years, and cardiac conduction disturbances need to be observed during surgery.[38] Ibuprofen (Brufen®) should be given with care in those with evidence of cardiomyopathy and should be avoided in those with congestive heart failure.[37]

In conclusion, before scoliosis surgery look at the eyes and face of the child to avoid unpleasant surprises.

Janicki JA, Alman B. Scoliosis: Review of diagnosis and treatment. Paediatr Child Health 2007;12:771-6.
[Google Scholar]
Popko J, Kwiatkowski M, Galczyk M. Scoliosis: Review of diagnosis and treatment. Pol J Appl Sci 2018;4:31-5.
[Google Scholar]
Roberts SB, Tsirikos AI. Factors influencing the evaluation and management of neuromuscular scoliosis: A review of the literature. J Back Musculoskelet Rehabil 2016;29:613-23.
[Google Scholar]
Vialle R, Thévenin-Lemoine C, Mary P. Neuromuscular scoliosis. Orthop Traumatol Surg Res 2013;99 Suppl 1:S124-39.
[Google Scholar]
Brooks JT, Sponseller PD. What's new in the management of neuromuscular scoliosis. J Pediatr Orthop 2016;36:627-33.
[Google Scholar]
Salih MA. Approach to diagnosis and treatment of a child with motor unit diseases. In: Elzouki AY, Stapleton FB, Whitley RJ, Oh W, Nazer H, Harfi HA, editors. Textbook of Clinical Pediatrics. 2nd ed. New York: Springer-Verlag; 2012. p. 3445-55.
[Google Scholar]
Salih MA. Anterior horn cell diseases. In: Elzouki AY, Stapleton FB, Whitley RJ, Oh W, Nazer H, Harfi HA, editors. Textbook of Clinical Pediatrics. 2nd ed. New York: Springer-Verlag; 2012. p. 3463-9.
[Google Scholar]
Salih MA. Peripheral nerve disorders. In: Elzouki AY, Stapleton FB, Whitley RJ, Oh W, Nazer H, Harfi HA, editors. Textbook of Clinical Pediatrics. 2nd ed. New York: Springer-Verlag; 2012. p. 3475-91.
[Google Scholar]
Salih MA. Hereditary and acquired myopathies. In: Elzouki AY, Stapleton FB, Whitley RJ, Oh W, Nazer H, Harfi HA, editors. Textbook of Clinical Pediatrics. New York: Springer-Verlag; 2012. p. 3503-41.
[Google Scholar]
Bird TD. Charcot-Marie-tooth neuropathy type 4. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, editors. Genereviews®. Seattle (WA): University of Washington, Seattle; 1993-2019. Available from: [Last updated on 2016 Apr 14].
[Google Scholar]
Salih MA, Maisonobe T, Kabiraj M, Al Rayess M, Al-Turaiki MH, Akbar M, et al. Autosomal recessive hereditary neuropathy with focally folded myelin sheaths and linked to chromosome 11q23: A distinct and homogeneous entity. Neuromuscul Disord 2000;10:10-5.
[Google Scholar]
Bolino A, Levy ER, Muglia M, Conforti FL, LeGuern E, Salih MA, et al. Genetic refinement and physical mapping of the CMT4B gene on chromosome 11q22. Genomics 2000;63:271-8.
[Google Scholar]
Bolino A, Muglia M, Conforti FL, LeGuern E, Salih MA, Georgiou DM, et al. Charcot-Marie-Tooth type 4B is caused by mutations in the gene encoding myotubularin-related protein-2. Nat Genet 2000;25:17-9.
[Google Scholar]
Dubourg O, Azzedine H, Verny C, Durosier G, Birouk N, Gouider R, et al. Autosomal-recessive forms of demyelinating Charcot-Marie-Tooth disease. Neuromolecular Med 2006;8:75-86.
[Google Scholar]
Azzedine H, Ravisé N, Verny C, Gabrëels-Festen A, Lammens M, Grid D, et al. Spine deformities in Charcot-Marie-tooth 4C caused by SH3TC2 gene mutations. Neurology 2006;67:602-6.
[Google Scholar]
Szigeti K, Wiszniewski W, Saifi GM, Sherman DL, Sule N, Adesina AM, et al. Functional, histopathologic and natural history study of neuropathy associated with EGR2 mutations. Neurogenetics 2007;8:257-62.
[Google Scholar]
Cossins J, Belaya K, Hicks D, Salih MA, Finlayson S, Carboni N, et al. Congenital myasthenic syndromes due to mutations in ALG2 and ALG14. Brain 2013;136:944-56.
[Google Scholar]
Mihaylova V, Salih MA, Mukhtar MM, Abuzeid HA, El-Sadig SM, von der Hagen M, et al. Refinement of the clinical phenotype in musk-related congenital myasthenic syndromes. Neurology 2009;73:1926-8.
[Google Scholar]
Salih MA. Neuromuscular transmission disorders. In: Elzouki AY, Stapleton FB, Whitley RJ, Oh W, Nazer H, Harfi HA, editors. Textbook of Clinical Pediatrics. 2nd ed. New York: Springer-Verlag; 2012. p. 3493-502.
[Google Scholar]
Mihaylova V, Müller JS, Vilchez JJ, Salih MA, Kabiraj MM, D'Amico A, et al. Clinical and molecular genetic findings in COLQ-mutant congenital myasthenic syndromes. Brain 2008;131:747-59.
[Google Scholar]
Duran GS, Uzunhan TA, Ekici B, Çıtak A, Aydınlı N, Çalışkan M. Severe scoliosis in a patient with COLQ mutation and congenital myasthenic syndrome: A clue for diagnosis. Acta Neurol Belg 2013;113:531-2.
[Google Scholar]
Finsterer J. Congenital myasthenic syndromes. Orphanet J Rare Dis 2019;14:57.
[Google Scholar]
Salih MA, Oystreck DT, Al-Faky YH, Kabiraj M, Omer MI, Subahi EM, et al. Congenital myasthenic syndrome due to homozygous CHRNE mutations: Report of patients in Arabia. J Neuroophthalmol 2011;31:42-7.
[Google Scholar]
Richard P, Gaudon K, Haddad H, Ammar AB, Genin E, Bauché S, et al. The CHRNE 1293insG founder mutation is a frequent cause of congenital myasthenia in North Africa. Neurology 2008;71:1967-72.
[Google Scholar]
Emura M, Ishii H, Baba H. Anesthetic management of scoliosis surgery for a patient with congenital myasthenic syndrome. Masui 2014;63:911-4.
[Google Scholar]
Jen J, Coulin CJ, Bosley TM, Salih MA, Sabatti C, Nelson SF, et al. Familial horizontal gaze palsy with progressive scoliosis maps to chromosome 11q23-25. Neurology 2002;59:432-5.
[Google Scholar]
Jen JC, Chan WM, Bosley TM, Wan J, Carr JR, Rüb U, et al. Mutations in a human ROBO gene disrupt hindbrain axon pathway crossing and morphogenesis. Science 2004;304:1509-13.
[Google Scholar]
Bosley TM, Salih MA, Jen JC, Lin DD, Oystreck D, Abu-Amero KK, et al. Neurologic features of horizontal gaze palsy and progressive scoliosis with mutations in ROBO3. Neurology 2005;64:1196-203.
[Google Scholar]
Themistocleous GS, Sapkas GS, Papagelopoulos PJ, Stilianessi EV, Papadopoulos ECh, Apostolou CD. Scoliosis in Steinert syndrome: A case report. Spine J 2005;5:212-6.
[Google Scholar]
Nicole S, White PS, Topaloglu H, Beigthon P, Salih M, Hentati F, et al. The human CDC42 gene: Genomic organization, evidence for the existence of a putative pseudogene and exclusion as a SJS1 candidate gene. Hum Genet 1999;105:98-103.
[Google Scholar]
Salih MA. Muscular dystrophies and myopathies in Arab populations. In: Genetic Disorders among Arab Populations. Berlin, Heidelberg: Springer; 2010. p. 145-79.
[Google Scholar]
Seay AR, Ziter FA. Malignant hyperpyrexia in a patient with Schwartz-Jampel syndrome. J Pediatr 1978;93:83-4.
[Google Scholar]
de Oliveira Camacho FC, Lopes Amaral TM, de Barros Mourão JI. A successful anesthetic approach in a patient with Schwartz-Jampel syndrome. Saudi J Anaesth 2018;12:128-30.
[Google Scholar]
Hopkins PM. Malignant hyperthermia: Pharmacology of triggering. Br J Anaesth 2011;107:48-56.
[Google Scholar]
AlBakri A, Karaoui M, Alkuraya FS, Khan AO. Congenital ptosis, scoliosis, and malignant hyperthermia susceptibility in siblings with recessive RYR1 mutations. J AAPOS 2015;19:577-9.
[Google Scholar]
Monnier N, Marty I, Faure J, Castiglioni C, Desnuelle C, Sacconi S, et al. Null mutations causing depletion of the type 1 ryanodine receptor (RYR1) are commonly associated with recessive structural congenital myopathies with cores. Hum Mutat 2008;29:670-8.
[Google Scholar]
Hackman P, Savarese M, Carmignac V, Udd B, Salih MA. Salih myopathy. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, editors. Genereviews®. Seattle (WA): University of Washington, Seattle; 1993-2019. Available from: [Last updated on 2019 Apr 11].
[Google Scholar]
Carmignac V, Salih MA, Quijano-Roy S, Marchand S, Al Rayess MM, Mukhtar MM, et al. C-terminal titin deletions cause a novel early-onset myopathy with fatal cardiomyopathy. Ann Neurol 2007;61:340-51.
[Google Scholar]

Fulltext Views

PDF downloads
Show Sections