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Birth Defects Research Apr 2022Sacral agenesis (SA) consists of partial or complete absence of the caudal end of the spine and often presents with additional birth defects. Several studies have...
BACKGROUND
Sacral agenesis (SA) consists of partial or complete absence of the caudal end of the spine and often presents with additional birth defects. Several studies have examined gene variants for syndromic forms of SA, but only one has examined exomes of children with non-syndromic SA.
METHODS
Using buccal cell specimens from families of children with non-syndromic SA, exomes of 28 child-parent trios (eight with and 20 without a maternal diagnosis of pregestational diabetes) and two child-father duos (neither with diagnosis of maternal pregestational diabetes) were exome sequenced.
RESULTS
Three children had heterozygous missense variants in ID1 (Inhibitor of DNA Binding 1), with CADD scores >20 (top 1% of deleterious variants in the genome); two children inherited the variant from their fathers and one from the child's mother. Rare missense variants were also detected in PDZD2 (PDZ Domain Containing 2; N = 1) and SPTBN5 (Spectrin Beta, Non-erythrocytic 5; N = 2), two genes previously suggested to be associated with SA etiology. Examination of variants with autosomal recessive and X-linked recessive inheritance identified five and two missense variants, respectively. Compound heterozygous variants were identified in several genes. In addition, 12 de novo variants were identified, all in different genes in different children.
CONCLUSIONS
To our knowledge, this is the first study reporting a possible association between ID1 and non-syndromic SA. Although maternal pregestational diabetes has been strongly associated with SA, the missense variants in ID1 identified in two of three children were paternally inherited. These findings add to the knowledge of gene variants associated with non-syndromic SA and provide data for future studies.
Topics: Abnormalities, Multiple; Exome; Humans; Infant; Meningocele; Sacrococcygeal Region
PubMed: 35274497
DOI: 10.1002/bdr2.1987 -
Journal of Neurosurgery. Case Lessons Jun 2023Posterior cervical meningoceles are rare in adults because most are surgically excised early in life. Such meningoceles in adults are mostly presented as a cystic mass...
BACKGROUND
Posterior cervical meningoceles are rare in adults because most are surgically excised early in life. Such meningoceles in adults are mostly presented as a cystic mass and their presentation as a solid mass is very rare.
OBSERVATIONS
An asymptomatic adult with cervical meningocele presented as a congenital midline skin covered solid mass in the posterior aspect of the neck is presented. Neuroradiological surveys showed attachment of the mass to intradural spinal cord. With diagnosis of a cervical meningocele, after excision of the solid sac, the stalk extending from the core of the mass to the dura was isolated. This was followed by intradural spinal cord detethering. The mass was compatible with rudimentary meningocele in pathology.
LESSONS
Neglected cervical meningocele is quite rare in adults. Surgical removal of the mass in adults is usually for cosmetic reasons rather than neurological impairment. However, surgical removal of the mass without intradural cord detethering is not sufficient. In such cases, late onset quadriparesis may be appear due to the spinal cord tethering scenario.
PubMed: 37310698
DOI: 10.3171/CASE23152 -
Pediatric Neurosurgery 2020Lateral meningocele syndrome (LMS) is an exceedingly rare connective tissue disease with phenotypic anomalies similar to those seen in Marfan syndrome, Ehler-Danlos... (Review)
Review
BACKGROUND
Lateral meningocele syndrome (LMS) is an exceedingly rare connective tissue disease with phenotypic anomalies similar to those seen in Marfan syndrome, Ehler-Danlos syndrome, and Loeys-Dietz syndrome. However, this syndrome is invariably associated with the presence of multiple lateral thoracolumbar spinal meningoceles: a distinct point of phenotypic divergence from other connective tissue disorders. The etiopathogenesis of this syndrome has recently been linked to truncating mutations within exon 33 of NOTCH3. Despite numerous reports, neurosurgical management of multiple spinal meningoceles remains poorly defined in the literature. We conducted a literature review to provide insight into the nosology, clinical significance, and neurosurgical management strategies of this distinct connective tissue disorder.
SUMMARY
Our literature search revealed 11 articles (16 cases) of LMS, which included 9 males and 7 females, belonging to 14 different families. Half of these cases underwent genetic screening: all of which were discovered to exhibit a truncating mutation within exon 33 of NOTCH3. All patients exhibited multiple lateral thoracolumbar spinal meningoceles with craniofacial dysmorphisms. Other clinical characteristics included pathologic changes in spine morphology, Chiari I malformation, syringomyelia, hydrocephalus, and tethered cord. Operative management of multiple spinal meningoceles in LMS is complicated by the presence of such coexisting structural neurologic pathologies, which may alter cerebrospinal fluid flow dynamics and, ultimately, impact operative intervention. Key Messages: LMS is an exceedingly rare connective tissue disorder with severe spinal dural involvement. Neurosurgical management of multiple spinal meningoceles is complex, which is further complicated by the presence of coexisting neuropathology, such as pathologic transformation of spine morphology and Chiari I malformation. Patients with a connective tissue disorder phenotype found to have multiple spinal meningoceles on imaging studies may benefit from evaluation by a medical geneticist and a pediatric neurosurgeon.
Topics: Abnormalities, Multiple; Adolescent; Child; Child, Preschool; Female; Humans; Infant; Magnetic Resonance Imaging; Male; Meningocele; Neurosurgeons; Receptor, Notch3; Spine
PubMed: 31838470
DOI: 10.1159/000504060 -
Journal of AAPOS : the Official... Feb 2017Intraorbital meningoencephaloceles occur most commonly as a complication of traumatic orbital roof fractures. Nontraumatic congenital orbital meningoncephaloceles are...
Intraorbital meningoencephaloceles occur most commonly as a complication of traumatic orbital roof fractures. Nontraumatic congenital orbital meningoncephaloceles are very rare, with most secondary to destructive processes affecting the orbit and primary skull defects. Treatment for intraorbital meningoencephaloceles is surgical repair, involving the excision of herniated brain parenchyma and meninges and reconstruction of the osseous defect. Most congenital lesions present in infancy with obvious globe and orbital deformities; we report an orbital meningoencephalocele in a 3-year-old girl who presented with ptosis.
Topics: Blepharoptosis; Child, Preschool; Encephalocele; Female; Humans; Magnetic Resonance Imaging; Meningocele; Orbital Diseases; Tomography, X-Ray Computed
PubMed: 27993731
DOI: 10.1016/j.jaapos.2016.08.020 -
Neurology Dec 2022
Topics: Humans; Encephalocele; Meningocele; Nervous System Malformations; Meningitis, Bacterial; Meningitis
PubMed: 36127146
DOI: 10.1212/WNL.0000000000201335 -
Otology & Neurotology : Official... Mar 2018To study the clinical presentation, intraoperative findings and surgical management in meningo-encephalic-herniation (MEH) based on the etiology.
OBJECTIVE
To study the clinical presentation, intraoperative findings and surgical management in meningo-encephalic-herniation (MEH) based on the etiology.
STUDY DESIGN
A retrospective clinical study and is a follow-up on the previously published report in 2009.
SETTING
A quaternary referral otology and skull base center PATIENTS AND METHODS:: The inclusion criteria were intraoperatively verified MEH in patients with a minimum follow-up of 12 months, which yielded 262 operated ears. The data were extracted regarding demographics, laterality, clinical presentation, past surgeries, contralateral-ear condition, intraoperative findings, complications, recurrences, revision-surgeries, audiometric-data, and follow-up.
RESULTS
The mean age at surgery was 49.7 years with the involvement of right-ear in 53.8% of patients. Lesions were categorized based on the etiology as chronic-otitis-media with/without cholesteatoma-MEH (COM/CHOL-MEH)-47.7%, iatrogenic-MEHs -20.9%; traumatic-MEHs -8% and spontaneous-MEHs -23.3%. At presentation, hearing loss (100 and 98.2%) and otorrhea (65.6 and 49.1%) were predominant in COM/CHOL-MEHs and iatrogenic-MEHs, respectively. On the other hand, meningitis (23.9 and 14.3%) and cerebrospinal fluid-leak (52.4 and 42.8%) were more pronounced in spontaneous and traumatic MEHs, respectively. Surgical approaches included 1) transmastoid, 2) middle-cranial-fossa-approach, 3) combined, and 4) middle-ear-obliteration (MEO) techniques. A total of 52.8% of COM/CHOL-MEHs and 49.1% of iatrogenic-MEHs underwent MEO. Middle-cranial-fossa approach was predominantly used in spontaneous-MEHs (52.5%) and traumatic-MEHs (38.1%). The defect was mostly single (75.2%). Smaller, multiple, bilateral lesions were more common in spontaneous-MEHs with tegmen-tympani involvement (57.4%).
CONCLUSION
Incorporating etiology into MEHs is a key-step that can be used as a guidance in choosing the right surgery. MEO is a part of armamentarium, and should be used whenever needed, if the objective is performing a definitive surgery.
Topics: Adult; Aged; Encephalocele; Female; Humans; Male; Meningocele; Middle Aged; Neurosurgical Procedures; Recurrence; Retrospective Studies; Temporal Bone; Young Adult
PubMed: 29424819
DOI: 10.1097/MAO.0000000000001693 -
Otolaryngology--head and Neck Surgery :... Jul 2024To review surgical techniques used in the endoscopic transnasal repair of pediatric basal meningoencephaloceles and compare perioperative outcomes in children <2 and... (Review)
Review
OBJECTIVE
To review surgical techniques used in the endoscopic transnasal repair of pediatric basal meningoencephaloceles and compare perioperative outcomes in children <2 and ≥2 years old.
DATA SOURCES
MEDLINE, EMBASE, and CENTRAL.
REVIEW METHODS
Data sources were searched from inception to August 22, 2022, using search terms relevant to endoscopic transnasal meningoencephalocele repair in children. Reviews and Meta-analyses were excluded. Primary outcomes were the incidence of intraoperative and postoperative complications, including cerebrospinal fluid leak, recurrence, and reintervention. Quality assessments were performed using Newcastle-Ottawa Scale, ROBIN-I, and NIH.
RESULTS
Overall, 217 patients across 61 studies were identified. The median age at surgery was 4 years (0-18 years). Fifty percent were female; 31% were <2 years. Most defects were meningoencephaloceles (56%), located transethmoidal (80%), and of congenital origin (83%). Seventy-five percent of repairs were multilayered. Children ≥2 years underwent multilayer repairs more frequently than those <2 years (P = 0.004). Children <2 years more frequently experienced postoperative cerebrospinal fluid leaks (P = 0.02), meningoencephalocele recurrence (P < 0.0001), and surgical reintervention (P = 0.005). Following multilayer repair, children <2 years were more likely to experience recurrence (P = 0.0001) and reintervention (P = 0.006).
CONCLUSION
Younger children with basal meningoencephaloceles appear to be at greater risk of postoperative complications following endoscopic endonasal repair, although the quality of available evidence is weakened by incomplete reporting. In the absence of preoperative cerebrospinal fluid leak or meningitis, it may be preferable to delay surgery as access is more conducive to successful repair in older children.
Topics: Adolescent; Child; Child, Preschool; Female; Humans; Infant; Encephalocele; Endoscopy; Meningocele; Natural Orifice Endoscopic Surgery; Nose; Postoperative Complications; Male; Infant, Newborn
PubMed: 38494838
DOI: 10.1002/ohn.711 -
The Journal of Biological Chemistry Sep 2018Lateral meningocele syndrome (LMS) is a rare genetic disorder characterized by neurological complications and osteoporosis. LMS is associated with mutations in exon 33...
Lateral meningocele syndrome (LMS) is a rare genetic disorder characterized by neurological complications and osteoporosis. LMS is associated with mutations in exon 33 of leading to a truncated protein lacking sequences for NOTCH3 degradation and presumably causing NOTCH3 gain of function. To create a mouse model reproducing human LMS-associated mutations, we utilized CRISPR/Cas9 to introduce a tandem termination codon at bases 6691-6696 (ACCAAG→TAATGA) and verified this mutation ( ) by DNA sequencing of F1 mice. One-month-old male and female heterozygous mice had cancellous and cortical bone osteopenia but exhibited no obvious neurological alterations, and histopathology of multiple organs revealed no abnormalities. Microcomputed tomography of these mutants revealed a 35-60% decrease in cancellous bone volume associated with a reduction in trabecular number and decreased connectivity. During maturation, cancellous and cortical bones were restored in female but not in male mice, which exhibited cancellous bone osteopenia at 4 months. Cancellous bone histomorphometry revealed increased osteoblast and osteocyte numbers and a modest increase in osteoclast surface and bone formation rate. calvarial osteoblasts had increased proliferation and increased bone γ-carboxyglutamate protein () and TNF superfamily member 11 () mRNA levels and lower levels. mRNA was increased in osteocyte-rich femora from mice. Cultures of bone marrow-derived macrophages from mice revealed increased osteoclast formation, particularly in cocultures with osteoblasts from mice. In conclusion, the mutation causes osteopenia despite an increase in osteoblast proliferation and function and is associated with enhanced expression in osteoblasts and osteocytes.
Topics: Abnormalities, Multiple; Animals; Bone Diseases, Metabolic; Cancellous Bone; Female; Gain of Function Mutation; Macrophages; Male; Meningocele; Mice; Osteoblasts; Osteoclasts; Osteocytes; RANK Ligand; Receptor, Notch3
PubMed: 30042232
DOI: 10.1074/jbc.RA118.004242 -
Child's Nervous System : ChNS :... Nov 2015The present study aimed to investigate the relationship between meningocele and tethered cord syndrome, diagnosis of meningocele associated with tethered cord syndrome,...
PURPOSE
The present study aimed to investigate the relationship between meningocele and tethered cord syndrome, diagnosis of meningocele associated with tethered cord syndrome, and when to perform surgery and the best surgical procedure.
METHODS
Sixty-nine children with meningocele who were admitted to Shanghai Children's Medical Center were analyzed. The relationship between meningocele and other lesions causing tethered cord syndrome was studied by combining magnetic resonance imaging (MRI) and intraoperative findings.
RESULTS
The MRI results and intraoperative findings showed that 67 children (97%) had associated lesions such as tight filum terminale, fibrous band tethering, spinal cord or cauda equina adhesion, diastematomyelia, arachnoid cyst, and epidermoid cyst. The protruded meninges were repaired, and the intraspinal lesions were treated at the same time. Also, the tethered spinal cord was released. No neurological injuries were observed after surgery.
CONCLUSIONS
The rate of meningocele associated with tethered cord syndrome is very high. MRI is necessary for the diagnosis of meningocele. Active surgical treatment is recommended immediately after definite diagnosis. During surgery, the surgeon should not only repair the protruded meninges but also explore the spinal canal and release the tethered cord.
Topics: Cauda Equina; Child; Child, Preschool; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Magnetic Resonance Imaging; Male; Medulla Oblongata; Meninges; Meningocele; Neural Tube Defects; Retrospective Studies
PubMed: 26298824
DOI: 10.1007/s00381-015-2874-4 -
Journal of Neurosurgery. Pediatrics Mar 2021Trigeminal meningocele is a rare disease that results in rhinorrhea. Treatments with endoscopic approaches and open craniotomies have high recurrence rates, and...
Trigeminal meningocele is a rare disease that results in rhinorrhea. Treatments with endoscopic approaches and open craniotomies have high recurrence rates, and controversy regarding the most effective surgical strategy for trigeminal meningocele is ongoing. The authors report a case of a 13-year-old female patient with a diagnosis of trigeminal meningocele determined after she presented with a history of intermittent headaches, suspected rhinorrhea, and recurrent meningitis. In addition to the conventional method of covering the efflux point of CSF and filling the inside of the meningocele with fascial tissues, the authors selectively closed the influx point of CSF from the prepontine cistern to the meningocele using an anterior transpetrosal approach. On the basis of the preoperative images, the authors hypothesized that the influx point of CSF could not be observed under the microscopic direct view and instead used a flexible endoscope. A check valve-like structure with one-way communication of CSF from the prepontine cistern into the cystic cavity was identified and was closed. At the time of this report, 36 months postoperatively, the patient had no indications of recurrence. Although cases of trigeminal meningoceles are infrequently encountered and require a tailored approach, the results in this case thus far indicate that the use of an endoscope and open craniotomy is an effective strategy for surgical treatment.
Topics: Adolescent; Cerebrospinal Fluid Rhinorrhea; Craniotomy; Female; Humans; Meningocele; Microsurgery; Neuroendoscopy
PubMed: 33711806
DOI: 10.3171/2020.9.PEDS20259