Neurosurgical management of symptomatic thoracic spinal ossification in a patient with fibrodysplasia ossificans progressiva

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder characterized by heterotopic ossification of soft connective and muscle tissues, often as the result of minor trauma. The sequelae include joint fusion, accumulation of calcified foci within soft tissues, thoracic insufficiency syndrome, and progressive immobility. The authors report on a patient with FOP who developed severe spinal canal stenosis in the thoracic spine causing substantial myelopathy. He underwent a thoracic laminectomy and resection of a large posterior osteophyte. Unique considerations are required in treating patients with FOP, including steroid administration to prevent ossification and anesthetic technique. The nuances of neurosurgical and medical management as they pertain to this disease are discussed.

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Mutant Activin-Like Kinase 2 in Fibrodysplasia Ossificans Progressiva are Activated via T203 by BMP Type II Receptors

Molecular Endocrinology ◽

10.1210/me.2014-1301 ◽

2015 ◽

Vol 29 (1) ◽

pp. 140-152 ◽

Cited By ~ 19

Author(s):

Mai Fujimoto ◽

Satoshi Ohte ◽

Kenji Osawa ◽

Arei Miyamoto ◽

Sho Tsukamoto ◽

...

Keyword(s):

Bone Morphogenetic Proteins ◽

Intracellular Signaling ◽

Molecular Mechanisms ◽

Soft Tissues ◽

Genetic Disorder ◽

Fibrodysplasia Ossificans Progressiva ◽

Type I ◽

Type Ii ◽

Activin Receptor ◽

Bmp Receptors

Abstract Fibrodysplasia ossificans progressiva (FOP) is a genetic disorder characterized by progressive heterotopic ossification in soft tissues, such as the skeletal muscles. FOP has been shown to be caused by gain-of-function mutations in activin receptor-like kinase (ALK)-2, which is a type I receptor for bone morphogenetic proteins (BMPs). In the present study, we examined the molecular mechanisms that underlie the activation of intracellular signaling by mutant ALK2. Mutant ALK2 from FOP patients enhanced the activation of intracellular signaling by type II BMP receptors, such as BMPR-II and activin receptor, type II B, whereas that from heart disease patients did not. This enhancement was dependent on the kinase activity of the type II receptors. Substitution mutations at all nine serine and threonine residues in the ALK2 glycine- and serine-rich domain simultaneously inhibited this enhancement by the type II receptors. Of the nine serine and threonine residues in ALK2, T203 was found to be critical for the enhancement by type II receptors. The T203 residue was conserved in all of the BMP type I receptors, and these residues were essential for intracellular signal transduction in response to ligand stimulation. The phosphorylation levels of the mutant ALK2 related to FOP were higher than those of wild-type ALK2 and were further increased by the presence of type II receptors. The phosphorylation levels of ALK2 were greatly reduced in mutants carrying a mutation at T203, even in the presence of type II receptors. These findings suggest that the mutant ALK2 related to FOP is enhanced by BMP type II receptors via the T203-regulated phosphorylation of ALK2.

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Thoracic Insufficiency Syndrome in Patients With Fibrodysplasia Ossificans Progressiva

Clinical Reviews in Bone and Mineral Metabolism ◽

10.1385/bmm:3:3-4:213 ◽

2005 ◽

Vol 3 (3-4) ◽

pp. 213-216 ◽

Cited By ~ 44

Author(s):

Frederick S. Kaplan ◽

David L. Glaser

Keyword(s):

Fibrodysplasia Ossificans Progressiva ◽

Thoracic Insufficiency Syndrome ◽

Insufficiency Syndrome

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Fibrodysplasia Ossificans Progressiva and Its Implications in Podiatric Medicine: A Case Report

Journal of the American Podiatric Medical Association ◽

10.7547/18-021 ◽

2019 ◽

Vol 109 (4) ◽

pp. 317-321

Author(s):

Nicholas Bolognini ◽

Neil Navendu Trivedi ◽

Andrew S. Au ◽

Nishit Vora

Keyword(s):

Case Report ◽

Endochondral Ossification ◽

Pediatric Patients ◽

Soft Tissues ◽

Clinical Presentation ◽

Genetic Disorder ◽

Surgical Excision ◽

Fibrodysplasia Ossificans Progressiva ◽

Irreversible Damage ◽

Dental Procedures

The purpose of this case report is to show the clinical presentation of a rare genetic disorder, called fibrodysplasia ossificans progressiva, on the development of the foot in a newborn. Shortened great toes and malformations of the first metatarsals are present in all affected individuals at birth. Irreversible heterotopic endochondral ossification of soft tissues occurs in the first decade of life, often resulting in permanent immobility by the third decade of life. Trauma caused by surgical excision of nodules, dental procedures, or injections can further exacerbate this condition. Early diagnosis is imperative for these patients to prevent irreversible damage that may result from unnecessary invasive interventions. This case report presents a boy aged 2 years 3 months who was born with bilateral bunion deformity. The goal is to raise awareness of this disorder in the podiatric community, especially for those who work with pediatric patients.

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Conductive Hearing Loss in Individuals with Fibrodysplasia Ossificans Progressiva

American Journal of Audiology ◽

10.1044/1059-0889(1999/011) ◽

1999 ◽

Vol 8 (1) ◽

pp. 29-33 ◽

Cited By ~ 25

Author(s):

Charles E. Levy ◽

Albert T. Lash ◽

Hal B. Janoff ◽

Frederick S. Kaplan

Keyword(s):

Hearing Loss ◽

Heterotopic Ossification ◽

Congenital Malformation ◽

Large Scale ◽

Soft Tissues ◽

Conductive Hearing Loss ◽

Genetic Disorder ◽

Postal Survey ◽

Fibrodysplasia Ossificans Progressiva ◽

Conductive Hearing

Fibrodysplasia ossificans progressiva (FOP) is a very rare genetic disorder that is characterized by progressive heterotopic ossification of soft tissues and congenital malformation of the great toes. Although previous case studies have reported hearing loss in individuals with FOP, there have been no large-scale studies regarding the nature or cause of the hearing loss. Here, we report the findings of a two-part study. In Part I, we report the findings of a postal survey regarding hearing loss that was sent to 102 individuals with FOP. In Part II, we report the findings of on-site hearing evaluations of eight individuals with FOP. The findings of both studies indicate that individuals with FOP are at risk for hearing loss and that the type of loss is predominantly conductive in nature, similar to that seen in individuals who have otosclerosis.

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Thoracic spinal canal stenosis

Journal of Neurosurgery ◽

10.3171/jns.1987.66.3.0338 ◽

1987 ◽

Vol 66 (3) ◽

pp. 338-344 ◽

Cited By ~ 52

Author(s):

Gene H. Barnett ◽

Russell W. Hardy ◽

John R. Little ◽

Janet W. Bay ◽

George W. Sypert

Keyword(s):

Spinal Canal ◽

Lower Limbs ◽

Minor Trauma ◽

Thoracic Myelopathy ◽

Disc Protrusion ◽

Content Type ◽

Canal Stenosis ◽

Thoracic Spinal ◽

Thoracic Disc ◽

Fine Print

✓ Hypertrophy of the posterior spinal elements leading to compromise of the spinal canal and its neural elements is a well-recognized pathological entity affecting the lumbar or cervical spine. Such stenosis of the thoracic spine in the absence of a generalized rheumatological, metabolic, or orthopedic disorder, or a history of trauma is generally considered to be rare. Over a 2-year period the authors have treated six cases of thoracic myelopathy associated with thoracic canal stenosis. In four patients the deficits developed gradually and painlessly. The three older patients had a clinical profile characterized by complaints of pseudoclaudication, spastic lower limbs, and evidence of posterior column dysfunction. Two patients were younger adults with low thoracic myelopathy associated with local back pain after minor trauma. Both patients also had congenital narrowing of the thoracic spinal canal. Oil and metrizamide contrast myelography in the prone position were of limited value in diagnosing this condition; in fact, myelography may be misleading and result in erroneous diagnosis of thoracic disc protrusion, when the principal problem is dorsal and lateral compression from hypertrophied facets. Magnetic resonance imaging and computerized tomography sector scanning were more useful in the diagnosis of this disorder than was myelography. Thoracic canal stenosis may be more common than is currently recognized and account for a portion of the failures in anterior and lateral decompression of thoracic disc herniations.

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Cardiopulmonary and Neurologic Dysfunctions in Fibrodysplasia Ossificans Progressiva

Biomedicines ◽

10.3390/biomedicines9020155 ◽

2021 ◽

Vol 9 (2) ◽

pp. 155

Author(s):

Fatima Khan ◽

Xiaobing Yu ◽

Edward C. Hsiao

Keyword(s):

Central Nervous System ◽

Pulmonary Hypertension ◽

Bone Morphogenetic Proteins ◽

Fibrodysplasia Ossificans Progressiva ◽

Extensive Literature ◽

Receptor Sensitivity ◽

Heterotopic Ossifications ◽

Thoracic Insufficiency Syndrome ◽

The Central Nervous System ◽

Insufficiency Syndrome

Fibrodysplasia Ossificans Progressiva (FOP) is an ultra-rare but debilitating disorder characterized by spontaneous, progressive, and irreversible heterotopic ossifications (HO) at extraskeletal sites. FOP is caused by gain-of-function mutations in the Activin receptor Ia/Activin-like kinase 2 gene (Acvr1/Alk2), with increased receptor sensitivity to bone morphogenetic proteins (BMPs) and a neoceptor response to Activin A. There is extensive literature on the skeletal phenotypes in FOP, but a much more limited understanding of non-skeletal manifestations of this disease. Emerging evidence reveals important cardiopulmonary and neurologic dysfunctions in FOP including thoracic insufficiency syndrome, pulmonary hypertension, conduction abnormalities, neuropathic pain, and demyelination of the central nervous system (CNS). Here, we review the recent research and discuss unanswered questions regarding the cardiopulmonary and neurologic phenotypes in FOP.

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Anesthesia in Carvajal syndrome; the first case report

Anaesthesia, Pain & Intensive Care ◽

10.35975/apic.v24i1.1233 ◽

2020 ◽

Vol 24 (1) ◽

pp. 105-107

Author(s):

Sedighe Shahhosseini ◽

Reza Aminnejad ◽

Amir Shafa ◽

Mehrdad Memarzade

Keyword(s):

Intensive Care ◽

Case Report ◽

Surgical Resection ◽

Genetic Disorder ◽

Anesthetic Technique ◽

Close Monitoring ◽

Anesthesia Management ◽

Rare Genetic Disorder ◽

First Case ◽

Anesthetic Considerations

Carvajal syndrome is a rare genetic disorder. Patients reporting for surgery pose some difficulties in anesthesia management. In this case report we present the case of a 12-year-old boy, who was a known case of Carvajal syndrome, referred for surgical resection of perianal condyloma. Close monitoring of hemodynamic status is the mainstay of anesthetic considerations in such patients. As in any other challenging scenario, it should be kept in mind that ‘there is no safest anesthetic agent, nor the safest anesthetic technique; there is only the safest anesthesiologist’. Citation: Shahhosseini S, Aminnejad R, Shafa A, Memarzadeh M. Anesthesia in Carvajal syndrome; the first case report. Anaesth pain intensive care 2020;24(1):___ DOI: https://doi.org/10.35975/apic.v24i1.

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Single-level bilateral facet joint hypertrophy causing thoracic spinal canal stenosis

Journal of Clinical Neuroscience ◽

10.1016/j.jocn.2008.10.023 ◽

2009 ◽

Vol 16 (10) ◽

pp. 1363-1365 ◽

Cited By ~ 5

Author(s):

Andy Lim ◽

Paul D’Urso

Keyword(s):

Spinal Canal ◽

Facet Joint ◽

Spinal Canal Stenosis ◽

Single Level ◽

Canal Stenosis ◽

Thoracic Spinal

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Traumatic lumbar spondylolisthesis resulting in complete thoracic spinal cord avulsion: an unusual presentation

Journal of Neurosurgery Spine ◽

10.3171/2018.5.spine17919 ◽

2018 ◽

Vol 29 (6) ◽

pp. 635-638

Author(s):

Jamie Toms ◽

David L. Boyer ◽

Craig R. Kelman ◽

Rafael A. Vega

Keyword(s):

Soft Tissues ◽

Unusual Presentation ◽

Thoracic Spinal Cord ◽

Lumbar Drain ◽

First Case ◽

Thoracic Spinal ◽

Initial Imaging ◽

Lumbar Spondylolisthesis ◽

A Site ◽

Traumatic Spondylolisthesis

Traumatic spondylolisthesis is a known occurrence in trauma, but complete cord transection is relatively rare. Moreover, complete cord transection at a site distant from the traumatic spondylolisthesis without spondyloptosis is exceedingly rare. In this report, authors describe the first case of thoracic cord avulsion following a traumatic grade II lumbar spondylolisthesis. The unusual presentation of this case highlights the importance of further evaluating patients with neurological symptoms out of proportion with the injuries seen on initial imaging. Magnetic resonance imaging performed after initial imaging studies demonstrated T11 cord transection with the distal cord herniating into the lumbar paraspinal soft tissues, thus allowing for preoperative planning to prepare for a more significant intervention including complex dural repair and lumbar drain placement, in addition to instrumented fusion to stabilize the traumatic spondylolisthesis.

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