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Bone Nov 2022Mutations in CRTAP lead to an extremely rare form of recessive osteogenesis imperfecta (OI). CRTAP deficient mice have a brachycephalic skull, fusion of facial bones,...
Mutations in CRTAP lead to an extremely rare form of recessive osteogenesis imperfecta (OI). CRTAP deficient mice have a brachycephalic skull, fusion of facial bones, midface retrusion and class III dental malocclusion, but in humans, the craniofacial and dental phenotype has not been reported in detail. Here, we describe craniofacial and dental findings in two 11-year-old girls with biallelic CRTAP mutations. Patient 1 has a homozygous c.472-1021C>G variant in CRTAP intron 1 and a moderately severe OI phenotype. The variant is known to create a cryptic splice site, leading to a frameshift and nonsense-mediated RNA decay. Patient 1 started intravenous bisphosphonate treatment at 2 years of age. At age 11 years, height Z-score was +0.6. She had a short and wide face, concave profile and class III malocclusion, with a prognathic mandible and an antero-posterior crossbite. A panoramic radiograph showed a poor angulation of the second upper right premolar, and no dentinogenesis imperfecta or dental agenesis. Cone-beam computed tomography confirmed these findings and did not reveal any other abnormalities. Patient 2 has a homozygous CRTAP deletion of two amino acids (c.804_809del, p.Glu269_Val270del) and a severe OI phenotype. As previously established, the variant leads to instability of CRTAP protein. Intravenous bisphosphonate treatment was started at the age of 15 months. At 11 years of age her height Z-score was -9.7. She had a long and narrow face and convex profile, maxillary retrusion leading to a class III malocclusion, an edge-to-edge overjet and lateral open bite. Panoramic radiographs showed no dental abnormalities. Cone-beam computed tomography showed occipital bossing, platybasia and wormian bones. In these two girls with CRTAP mutations, the severity of the skeletal phenotype was mirrored in the severity of the craniofacial phenotype. Class III malocclusion and antero-posterior crossbite were a common trait, while dental agenesis or dentinogenesis imperfecta were not detected.
Topics: Amino Acids; Animals; Child; Diphosphonates; Extracellular Matrix Proteins; Female; Humans; Infant; Malocclusion; Mice; Molecular Chaperones; Mutation; Osteogenesis Imperfecta; Phenotype; RNA Splice Sites; Skull
PubMed: 35970273
DOI: 10.1016/j.bone.2022.116516 -
Surgical Neurology International 2019Craniometric studies document different subtypes of craniocervical junction malformations (CCJM). Here, we identified the different types and global signs and symptoms...
BACKGROUND
Craniometric studies document different subtypes of craniocervical junction malformations (CCJM). Here, we identified the different types and global signs and symptoms (SS) that correlated with these malformations while further evaluating the impact of syringomyelia.
METHODS
Prospective data concerning SS and types of CCJM were evaluated in 89 patients between September 2002 and April 2014 using Bindal's scale.
RESULTS
The mean Bindal's scores of each type of CCJM were Chiari malformation (CM) = 74.6, basilar invagination Type 1 (BI1) = 78.5, and BI Type 2 (BI2) = 78. Swallowing impairment and nystagmus were more frequently present in the BI patients. Symptomatic burdens were higher in patients with syringomyelia and included weakness, extremity numbness, neck pain, dissociated sensory loss, and atrophy.
CONCLUSION
There were no statistically significant differences in SS between the different CCJM types. BI patients had more swallowing and nystagmus complaints versus CM patients, but there were no significant differences in clinical SS between BI1 and BI2 patients. Notably, those with attendant syringomyelia had a higher SS burden.
PubMed: 31768286
DOI: 10.25259/SNI_469_2019 -
The Journal of Spinal Cord Medicine Nov 2022Spinal-generated movement disorders are a complex group of medical conditions, frequently misdiagnosed, originating in the spinal cord or from combined peripheral and...
CONTEXT
Spinal-generated movement disorders are a complex group of medical conditions, frequently misdiagnosed, originating in the spinal cord or from combined peripheral and central nervous system involvement. In this case report, we describe a novel form of position-dependent dyskinesia due to severe craniocervical malformation.
FINDINGS
An 83-year-old woman with basilar invagination at the C2 vertebra above the line of Chamberlain, occipitocervical lordosis, platybasia with a short clivus, ankylosis of the C1-C2 complex and fusion of the C1 arch developed an unusual pattern of position-dependent left arm dyskinesia triggered by bending her neck forward with simultaneous contact of the flexed elbow with a flat surface. Symptoms did not improve with anticonvulsants and she progressed and died suddenly.
CONCLUSION/CLINICAL RELEVANCE
A newly described form of position-dependent arm dyskinesia can be associated with severe craniocervical malformation.
Topics: Humans; Female; Aged, 80 and over; Arm; Spinal Fusion; Spinal Cord Injuries; Platybasia; Dyskinesias
PubMed: 33705252
DOI: 10.1080/10790268.2021.1878341 -
World Neurosurgery: X Oct 2023Chiari malformation type 1 (CM-1) is characterized by cerebellar tonsil herniation through the foramen magnum and can be associated with additional craniovertebral...
BACKGROUND
Chiari malformation type 1 (CM-1) is characterized by cerebellar tonsil herniation through the foramen magnum and can be associated with additional craniovertebral junction anomalies (CVJA). The pathophysiology and treatment for CM-1 with CVJA (CM-CVJA) is debated.
OBJECTIVE
To evaluate the trends and outcomes of surgical interventions for patients with CM-CVJA.
METHODS
A systematic review of the literature was performed to obtain articles describing surgical interventions for patients with CM-CVJA. Articles included were case series describing surgical approach; reviews were excluded. Variables evaluated included patient characteristics, approach, and postoperative outcomes.
RESULTS
The initial query yielded 403 articles. Twelve articles, published between 1998-2020, met inclusion criteria. From these included articles, 449 patients underwent surgical interventions for CM-CVJA. The most common CVJAs included basilar invagination (BI) (338, 75.3%), atlantoaxial dislocation (68, 15.1%) odontoid process retroflexion (43, 9.6%), and medullary kink (36, 8.0%). Operations described included posterior fossa decompression (PFD), transoral (TO) decompression, and posterior arthrodesis with either occipitocervical fusion (OCF) or atlantoaxial fusion. Early studies described good results using combined ventral and posterior decompression. More recent articles described positive outcomes with PFD or posterior arthrodesis in combination or alone. Treatment failure was described in patients with PFD alone that later required posterior arthrodesis. Additionally, reports of treatment success with posterior arthrodesis without PFD was seen.
CONCLUSION
Patients with CM-CVJA appear to benefit from posterior arthrodesis with or without decompressive procedures. Further definition of the pathophysiology of craniocervical anomalies is warranted to identify patient selection criteria and ideal level of fixation.
PubMed: 37456684
DOI: 10.1016/j.wnsx.2023.100221 -
Journal of Clinical Orthopaedics and... Feb 2021A Prospective Study.
STUDY DESIGN
A Prospective Study.
OBJECTIVE
To assess results of posterior occipito-cervical decompression and fusion operated with intra-operative traction/manipulation and instrumented reduction in cases of Basilar Invagination(BI).
METHODS
Total 22 patients of 8-65 years with diagnosed BI were operated for posterior occipito-cervical fusion by intra-operative traction/manipulation and instrumented reduction. Fusion was done using autologous bone graft taken from iliac crest. Immediate post-operative, first month and then every 3 months' follow-up examination were done for minimum period of 2 years.
RESULTS
22 patients (10 males,12 females) with mean age of 23.9 years having BI were included. 11 patients had C1 occipitalization, 4 had platybasia and 9 had atlanto-axial dislocation (AAD). 1 patient with os odontoideum with kyphotic deformity expired on 4th postoperative day due to respiratory insufficiency (mortality rate 4.54%). Neurological improvement by at least by one grade according to RANAWAT's and/or NURICK'S scale was observed in 17/21 patients (80.95%). 3 patients remained static and 1 had neuro-worsening. Mean mJOA score of 13.14 improved to 16.24. All had reduction of dens below foramen magnum according to McRae, chamberlain line and Ranawat index. Bone graft fused in all patients as confirmed with CT scan and dynamic X-rays. 1 wound dehiscence and 1 asymptomatic implant loosening were seen on follow-up.
CONCLUSION
Surgical treatment of BI with intra-operative traction/manipulation, instrumented reduction and posterior occipito-cervical fusion can achieve good correction of radiology, functional performance and clinical neurology as well as excellent fusion rates without adverse effects of trans-oral surgery.
PubMed: 33680811
DOI: 10.1016/j.jcot.2020.11.016 -
European Journal of Medical Genetics Aug 2020Primrose syndrome (OMIM 259050) is a rare disorder characterised by macrocephaly with developmental delay, a recognisable facial phenotype, altered glucose metabolism,...
Primrose syndrome (OMIM 259050) is a rare disorder characterised by macrocephaly with developmental delay, a recognisable facial phenotype, altered glucose metabolism, and other features such as sensorineural hearing loss, short stature, and calcification of the ear cartilage. It is caused by heterozygous variants in ZBTB20, a member of the POK family of transcription repressors. Recently, this gene was shown to have a role in skeletal development through its action on chondrocyte differentiation by repression of SOX9. We describe five unrelated patients with Primrose syndrome and distinct skeletal features including multiple Wormian bones, platybasia, bitemporal bossing, bathrocephaly, slender bones, epiphyseal and spondylar dysplasia. The radiological abnormalities of the skull and the epiphyseal dysplasia were the most consistent findings. This novel constellation of skeletal features expands the phenotypic spectrum of the disorder.
Topics: Abnormalities, Multiple; Adolescent; Bone and Bones; Calcinosis; Child; Child, Preschool; Ear Diseases; Female; Humans; Intellectual Disability; Male; Muscular Atrophy; Nerve Tissue Proteins; Phenotype; SOXB1 Transcription Factors; Transcription Factors; Young Adult
PubMed: 32473227
DOI: 10.1016/j.ejmg.2020.103967 -
Neurosurgery Jan 2021Occipital-cervical fusion (OCF) and ventral decompression (VD) may be used in the treatment of pediatric Chiari-1 malformation (CM-1) with syringomyelia (SM) as adjuncts...
Occipital-Cervical Fusion and Ventral Decompression in the Surgical Management of Chiari-1 Malformation and Syringomyelia: Analysis of Data From the Park-Reeves Syringomyelia Research Consortium.
BACKGROUND
Occipital-cervical fusion (OCF) and ventral decompression (VD) may be used in the treatment of pediatric Chiari-1 malformation (CM-1) with syringomyelia (SM) as adjuncts to posterior fossa decompression (PFD) for complex craniovertebral junction pathology.
OBJECTIVE
To examine factors influencing the use of OCF and OCF/VD in a multicenter cohort of pediatric CM-1 and SM subjects treated with PFD.
METHODS
The Park-Reeves Syringomyelia Research Consortium registry was used to examine 637 subjects with cerebellar tonsillar ectopia ≥ 5 mm, syrinx diameter ≥ 3 mm, and at least 1 yr of follow-up after their index PFD. Comparisons were made between subjects who received PFD alone and those with PFD + OCF or PFD + OCF/VD.
RESULTS
All 637 patients underwent PFD, 505 (79.2%) with and 132 (20.8%) without duraplasty. A total of 12 subjects went on to have OCF at some point in their management (PFD + OCF), whereas 4 had OCF and VD (PFD + OCF/VD). Of those with complete data, a history of platybasia (3/10, P = .011), Klippel-Feil (2/10, P = .015), and basilar invagination (3/12, P < .001) were increased within the OCF group, whereas only basilar invagination (1/4, P < .001) was increased in the OCF/VD group. Clivo-axial angle (CXA) was significantly lower for both OCF (128.8 ± 15.3°, P = .008) and OCF/VD (115.0 ± 11.6°, P = .025) groups when compared to PFD-only group (145.3 ± 12.7°). pB-C2 did not differ among groups.
CONCLUSION
Although PFD alone is adequate for treating the vast majority of CM-1/SM patients, OCF or OCF/VD may be occasionally utilized. Cranial base and spine pathologies and CXA may provide insight into the need for OCF and/or OCF/VD.
Topics: Arnold-Chiari Malformation; Child; Cohort Studies; Decompression, Surgical; Female; Humans; Male; Spinal Fusion; Syringomyelia; Treatment Outcome
PubMed: 33313928
DOI: 10.1093/neuros/nyaa460 -
BMC Neurology May 2020We propose two new concepts, the Filum Disease (FD) and the Neuro-cranio-vertebral syndrome (NCVS), that group together conditions thus far considered idiopathic, such...
BACKGROUND
We propose two new concepts, the Filum Disease (FD) and the Neuro-cranio-vertebral syndrome (NCVS), that group together conditions thus far considered idiopathic, such as Arnold-Chiari Syndrome Type I (ACSI), Idiopathic Syringomyelia (ISM), Idiopathic Scoliosis (IS), Basilar Impression (BI), Platybasia (PTB) Retroflexed Odontoid (RO) and Brainstem Kinking (BSK).
METHOD
We describe the symptomatology, the clinical course and the neurological signs of the new nosological entities as well as the changes visible on imaging studies in a series of 373 patients.
RESULTS
Our series included 72% women with a mean age of 33.66 years; 48% of the patients had an interval from onset to diagnosis longer than 10 years and 64% had a progressive clinical course. The commonest symptoms were: headache 84%, lumbosacral pain 72%, cervical pain 72%, balance alteration 72% and paresthesias 70%. The commonest neurological signs were: altered deep tendon reflexes in upper extremities 86%, altered deep tendon reflexes in lower extremities 82%, altered plantar reflexes 73%, decreased grip strength 70%, altered sensibility to temperature 69%, altered abdominal reflexes 68%, positive Mingazzini's test 66%, altered sensibility to touch 65% and deviation of the uvula and/or tongue 64%. The imaging features most often seen were: altered position of cerebellar tonsils 93%, low-lying Conus medullaris below the T12L1 disc 88%, idiopathic scoliosis 76%, multiple disc disease 72% and syringomyelic cavities 52%.
CONCLUSIONS
This is a paradigm shift that opens up new paths for research and broadens the range of therapeutics available to these patients.
Topics: Adolescent; Adult; Aged; Arnold-Chiari Malformation; Brain Stem; Child; Child, Preschool; Female; Headache; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Platybasia; Scoliosis; Syringomyelia; Young Adult
PubMed: 32393196
DOI: 10.1186/s12883-020-01743-y -
Neurosciences (Riyadh, Saudi Arabia) Aug 2020To assess the correlation between craniovertebral junction (CVJ) abnormalities and syringomyelia in patients with Chiari malformation type-1 (CM1).
OBJECTIVE
To assess the correlation between craniovertebral junction (CVJ) abnormalities and syringomyelia in patients with Chiari malformation type-1 (CM1).
METHODS
This was a retrospective study including patients with CM1. Identification of cases was done by searching a radiology database at a university hospital from 2012 to 2017. Patients were divided into 2 groups based on whether CVJ abnormalities were present (CVJ+) or absent (CVJ-). The patients` demographic and clinical data were reviewed. All magnetic resonance imaging studies were examined by a certified neuroradiologist.
RESULTS
Sixty-four consecutive patients with CM1 were included. The mean age was 24+/-17 years; 59% were females. The CVJ+ group had more female patients (p=0.012). The most frequent CVJ abnormality was platybasia (71%), followed by short clivus (44%) and cervical kyphosis (33%). The CVJ abnormalities were more in Syringomyelia cases (p=0.045). However, the results were not significant when hydrocephalus cases were excluded.
CONCLUSION
Among CM1 patients, CVJ abnormalities were found more in patients with syringomyelia. Future studies with larger sample size are required to further study the correlation between CVJ abnormalities and both syringomyelia and hydrocephalus in CM1 patients.
Topics: Adult; Arnold-Chiari Malformation; Atlanto-Occipital Joint; Female; Humans; Male; Retrospective Studies; Syringomyelia; Young Adult
PubMed: 33130812
DOI: 10.17712/nsj.2020.4.20200008 -
Medicina (Kaunas, Lithuania) Apr 2024: To present a novel technique of treatment for a patient with basilar invagination. Basilar invagination (BI) is a congenital condition that can compress the... (Review)
Review
: To present a novel technique of treatment for a patient with basilar invagination. Basilar invagination (BI) is a congenital condition that can compress the cervicomedullary junction, leading to neurological deficits. Severe cases require surgical intervention, but there is debate over the choice of approach. The anterior approach allows direct decompression but carries high complication rates, while the posterior approach provides indirect decompression and offers good stability with fewer complications. : A 15-year-old boy with severe myelopathy presented to our hospital with neck pain, bilateral upper limb muscle weakness, and hand numbness persisting for 4 years. Additionally, he experienced increased numbness and gait disturbance three months before his visit. On examination, he exhibited hyperreflexia in both upper and lower limbs, muscle weakness in the bilateral upper limbs (MMT 4), bilateral hypoesthesia below the elbow and in both legs, mild urinary and bowel incontinence, and a spastic gait. Radiographs revealed severe basilar invagination (BI). Preoperative images showed severe BI and that the spinal cord was severely compressed with odontoid process. : The patient underwent posterior surgery with the C-arm free technique. All screws including occipital screws were inserted into the adequate position under navigation guidance. Reduction was achieved with skull rotation and distraction. A follow-up at one year showed the following results: Manual muscle testing results and sensory function tests showed almost full recovery, with bilateral arm recovery (MMT 5) and smooth walking. The cervical Japanese Orthopedic Association score of the patient improved from 9/17 to 16/17. Postoperative images showed excellent spinal cord decompression, and no major or severe complications had occurred. : Basilar invagination alongside Klippel-Feil syndrome represents a relatively uncommon condition. Utilizing a posterior approach for treating reducible BI with a C-arm-free technique proved to be a safe method in addressing severe myelopathy. This novel navigation technique yields excellent outcomes for patients with BI.
Topics: Humans; Male; Adolescent; Klippel-Feil Syndrome; Decompression, Surgical; Platybasia; Treatment Outcome; Spinal Cord Compression
PubMed: 38674263
DOI: 10.3390/medicina60040616