The Clinical and Genotypic Spectrum of Scoliosis in Multiple Pterygium Syndrome: A Case Series on 12 Children

Background: Multiple pterygium syndrome (MPS) is a genetically heterogeneous rare form of arthrogryposis multiplex congenita characterized by joint contractures and webbing or pterygia, as well as distinctive facial features related to diminished fetal movement. It is divided into prenatally lethal (LMPS, MIM253290) and nonlethal (Escobar variant MPS, MIM 265000) types. Developmental spine deformities are common, may present early and progress rapidly, requiring regular fo llow-up and orthopedic management. Methods: Retrospective chart review and prospective data collection were conducted at three hospital centers. Molecular diagnosis was confirmed with whole exome or whole genome sequencing. Results: This case series describes the clinical features and scoliosis treatment on 12 patients from 11 unrelated families. A molecular diagnosis was confirmed in seven; two with MYH3 variants and five with CHRNG. Scoliosis was present in all but our youngest patient. The remaining 11 patients spanned the spectrum between mild (curve ≤ 25°) and malignant scoliosis (≥50° curve before 4 years of age); the two patients with MYH3 mutations presented with malignant scoliosis. Bracing and serial spine casting appear to be beneficial for a few years; non-fusion spinal instrumentation may be needed to modulate more severe curves during growth and spontaneous spine fusions may occur in those cases. Conclusions: Molecular diagnosis and careful monitoring of the spine is needed in children with MPS.

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Diagnosis of Genetic White Matter Disorders by Singleton Whole-Exome and Genome Sequencing Using Interactome-Driven Prioritization

Neurology ◽

10.1212/wnl.0000000000013278 ◽

2022 ◽

pp. 10.1212/WNL.0000000000013278

Author(s):

Agatha Schlüter ◽

Agustí Rodríguez-Palmero ◽

Edgard Verdura ◽

Valentina Vélez-Santamaría ◽

Montserrat Ruiz ◽

...

Keyword(s):

White Matter ◽

Candidate Genes ◽

Genome Sequencing ◽

Molecular Diagnosis ◽

Diagnostic Yield ◽

Collaborative Study ◽

Case Series ◽

Genomic Analysis ◽

White Matter Disorders ◽

Whole Exome

Background and Objectives:Genetic white matter disorders (GWMD) are of heterogeneous origin, with more than a hundred causal genes identified to date. Classical targeted approaches achieve a molecular diagnosis in only half of all patients. Here we aim to determine the clinical utility of singleton whole-exome sequencing and whole-genome sequencing (sWES-WGS) interpreted with a phenotype- and interactome-driven prioritization algorithm to diagnose GWMD patients, while identifying novel phenotypes and candidate genes.Methods:A case series of patients of all ages with undiagnosed GWMD despite extensive standard-of-care paraclinical studies were recruited between April 2017 and December 2019 in a collaborative study at the Bellvitge Biomedical Research Institute (IDIBELL) and neurology units of tertiary Spanish hospitals. We ran sWES and WGS and applied our interactome-prioritization algorithm, based on the network expansion of a seed group of GWMD-related genes, derived from the HPO terms of each patient.Results:We received 126 patients (101 children and 25 adults), with ages ranging from 1 month to 74 years. We obtained a first molecular diagnosis by singleton WES in 59% of cases, which increased to 68% after annual reanalysis and reached 72% after WGS was performed in 16 of the remaining negative cases. We identified variants in 57 different genes among 91 diagnosed cases, with the most frequent being RNASEH2B, EIF2B5, POLR3A and PLP1; and a dual diagnosis underlying complex phenotypes in six families, underscoring the importance of genomic analysis to solve these cases. Finally, we discovered 9 candidate genes causing novel diseases, and propose additional putative novel candidate genes for yet-to-be discovered GWMD.Discussion:Our strategy enables a high diagnostic yield and is a good alternative to trio WES/WGS for GWMD. It shortens the time to diagnosis compared to the classical targeted approach, thus optimizing appropriate management. Furthermore, the interactome-driven prioritization pipeline enables the discovery of novel disease-causing genes and phenotypes, and predicts novel putative candidate genes, shedding light on etiopathogenic mechanisms that are pivotal for myelin generation and maintenance.

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Vocal Fold Injection Augmentation for Post-Airway Reconstruction Dysphonia: A Case Series

Annals of Otology Rhinology & Laryngology ◽

10.1177/00034894211012594 ◽

2021 ◽

pp. 000348942110125

Author(s):

Mathieu Bergeron ◽

John Paul Giliberto ◽

Meredith E. Tabangin ◽

Alessandro de Alarcon

Keyword(s):

Vocal Fold ◽

Care Center ◽

Case Series ◽

Retrospective Chart Review ◽

Pediatric Care ◽

Voice Perception ◽

Perceptual Evaluation ◽

Airway Reconstruction ◽

Vocal Fold Injection ◽

History Of

Objectives: Post airway reconstruction dysphonia (PARD) is common and has a significant effect on the quality of life of patients. Vocal fold injection augmentation (VFIA) is one treatment that can be used to improve glottic insufficiency in some patients. The goal of this study was to characterize the use and outcomes of VFIA for PARD. Methods: Retrospective chart review from January 2007 to July 2018 at a tertiary pediatric care center. Consecutive patients with PARD who underwent VFIA, who had a preoperative voice evaluation and a follow-up evaluation within 3 months after VFIA (fat, carboxymethylcellulose gel, hyaluronic acid). Results: Thirty-four patients (20 female) underwent VFIA. The mean age at the time of the injection was 13.6 years (SD 6.1). Twenty patients (58.8%) had a history of prematurity and a mean of 1.8 open airway surgeries. After injection, 29/34 patients (85.3%) noted a subjective voice improvement. The baseline Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) overall severity score decreased by a mean of 5.7 (SD = 19.6) points, P = .12. Total pediatric Voice Handicap Index (pVHI) improved by 6.0 (SD = 19.5) points, from 57.4 (SD = 20.0) to 51.4 (SD = 17.2), P = .09. Functional pVHI subscore demonstrated a significant improvement, with a decrease of 3.4 (SD = 7.3) points, P = .02. All procedures were performed as an overnight observation and no complication occurred. Conclusion: Patients with PARD represent a complex subset of patients. VFIA is a straightforward intervention that may improve voice perception. Many patients reported subjective improvement despite minimal objective measurement. Further work is warranted to elucidate the role of injection in management of PARD

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A national study of choanal atresia in tertiary care centers in Canada – part I: clinical presentation

Journal of Otolaryngology - Head and Neck Surgery ◽

10.1186/s40463-021-00517-x ◽

2021 ◽

Vol 50 (1) ◽

Author(s):

Josee Paradis ◽

Agnieszka Dzioba ◽

Hamdy El-Hakim ◽

Paul Hong ◽

Frederick K. Kozak ◽

...

Keyword(s):

Respiratory Distress ◽

Clinical Presentation ◽

Tertiary Care ◽

Choanal Atresia ◽

Case Series ◽

Retrospective Chart Review ◽

National Study ◽

Feeding Difficulties ◽

Presenting Symptoms ◽

Tertiary Care Centers

Abstract Background To evaluate the clinical presentation of choanal atresia (CA) in tertiary centers across Canada. Methods Multi-centre case series involving six tertiary care pediatric hospitals across Canada. Retrospective chart review of patients born between 1980 and 2010 diagnosed with CA at a participating center. Results The health charts of 215 patients (59.6% female) with CA were reviewed and included in this study. The mean age of patients at time of CA presentation was 0.4 months (range 0.1 to 7.2 months) for bilateral CA and 37.8 months (range 0.1 to 164.1 months) for unilateral cases. The most common presenting symptoms for bilateral CA in decreasing order were respiratory distress (96.4%), feeding difficulties (68.2%), and rhinorrhea (65.5%), and for unilateral cases in decreasing order were rhinorrhea (92.0%), feeding difficulties (24.7%), and respiratory distress (18.0%). For the majority of patients (73.2%), the obstruction comprised mixed bony and membranous tissue, with only 10.5% presenting with a purely membranous obstruction. Familial history of CA was confirmed in only 3.3% of cases. One half of patients with CA presented with one or more associated anomalies and 30.6% had a syndrome. Conclusions The present investigation is the first national multi-institutional study evaluating the clinical presentation of CA over three decades. The present cohort of CA patients presented with a breadth of co-morbidities with highly variable presentations, with bilateral cases being more severely affected than unilateral cases. Further investigation into hereditary linkages to CA development is warranted. Graphical abstract

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The Increasing Impact of Translational Research in the Molecular Diagnostics of Neuromuscular Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms22084274 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4274

Author(s):

Dèlia Yubero ◽

Daniel Natera-de Benito ◽

Jordi Pijuan ◽

Judith Armstrong ◽

Loreto Martorell ◽

...

Keyword(s):

Molecular Diagnosis ◽

Clinical Symptoms ◽

Neuromuscular Diseases ◽

Genomic Analysis ◽

Molecular Diagnostic ◽

Diagnostic Process ◽

Targeted Analysis ◽

Whole Exome ◽

Referral Hospitals ◽

Uncertain Significance

The diagnosis of neuromuscular diseases (NMDs) has been progressively evolving from the grouping of clinical symptoms and signs towards the molecular definition. Optimal clinical, biochemical, electrophysiological, electrophysiological, and histopathological characterization is very helpful to achieve molecular diagnosis, which is essential for establishing prognosis, treatment and genetic counselling. Currently, the genetic approach includes both the gene-targeted analysis in specific clinically recognizable diseases, as well as genomic analysis based on next-generation sequencing, analyzing either the clinical exome/genome or the whole exome or genome. However, as of today, there are still many patients in whom the causative genetic variant cannot be definitely established and variants of uncertain significance are often found. In this review, we address these drawbacks by incorporating two additional biological omics approaches into the molecular diagnostic process of NMDs. First, functional genomics by introducing experimental cell and molecular biology to analyze and validate the variant for its biological effect in an in-house translational diagnostic program, and second, incorporating a multi-omics approach including RNA-seq, metabolomics, and proteomics in the molecular diagnosis of neuromuscular disease. Both translational diagnostics programs and omics are being implemented as part of the diagnostic process in academic centers and referral hospitals and, therefore, an increase in the proportion of neuromuscular patients with a molecular diagnosis is expected. This improvement in the process and diagnostic performance of patients will allow solving aspects of their health problems in a precise way and will allow them and their families to take a step forward in their lives.

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Stereotactic Electroencephalography Is Associated With Reduced Pain and Opioid Use When Compared with Subdural Grids: A Case Series

Operative Neurosurgery ◽

10.1093/ons/opab040 ◽

2021 ◽

Author(s):

Jonathan P Scoville ◽

Evan Joyce ◽

Joshua Hunsaker ◽

Jared Reese ◽

Herschel Wilde ◽

...

Keyword(s):

Hospital Stay ◽

Chart Review ◽

Statistical Tests ◽

Case Series ◽

Length Of Hospital Stay ◽

Retrospective Chart Review ◽

Opioid Use ◽

Pain Scores ◽

Surgical Methods ◽

Significant Difference

Abstract BACKGROUND Minimally invasive surgery (MIS) has been shown to decrease length of hospital stay and opioid use. OBJECTIVE To identify whether surgery for epilepsy mapping via MIS stereotactically placed electroencephalography (SEEG) electrodes decreased overall opioid use when compared with craniotomy for EEG grid placement (ECoG). METHODS Patients who underwent surgery for epilepsy mapping, either SEEG or ECoG, were identified through retrospective chart review from 2015 through 2018. The hospital stay was separated into specific time periods to distinguish opioid use immediately postoperatively, throughout the rest of the stay and at discharge. The total amount of opioids consumed during each period was calculated by transforming all types of opioids into their morphine equivalents (ME). Pain scores were also collected using a modification of the Clinically Aligned Pain Assessment (CAPA) scale. The 2 surgical groups were compared using appropriate statistical tests. RESULTS The study identified 43 patients who met the inclusion criteria: 36 underwent SEEG placement and 17 underwent craniotomy grid placement. There was a statistically significant difference in median opioid consumption per hospital stay between the ECoG and the SEEG placement groups, 307.8 vs 71.5 ME, respectively (P = .0011). There was also a significant difference in CAPA scales between the 2 groups (P = .0117). CONCLUSION Opioid use is significantly lower in patients who undergo MIS epilepsy mapping via SEEG compared with those who undergo the more invasive ECoG procedure. As part of efforts to decrease the overall opioid burden, these results should be considered by patients and surgeons when deciding on surgical methods.

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ALS-Like Disorder in Three HIV-Positive Patients: Case Series

Case Reports in Neurology ◽

10.1159/000511203 ◽

2021 ◽

pp. 59-64

Author(s):

Zachary Aaron Satin ◽

Elham Bayat

Keyword(s):

Antiretroviral Therapy ◽

Motor Neuron ◽

Motor Neuron Disease ◽

Motor Neurons ◽

Case Series ◽

Retrospective Chart Review ◽

Effective Control ◽

Hiv Positive ◽

Disease Course ◽

Retroviral Infection

There appears to be a relationship between retroviruses such as HIV and the development of an ALS-like syndrome. Few cases have been reported; however, there exists evidence of a higher frequency of motor neuron disease in HIV-infected patients, as well as potential slowing and reversibility of disease course with combination antiretroviral therapy. We conducted a retrospective chart review of patients presenting to the George Washington University ALS Clinic from September 2006 to June 2018 to identify patients with HIV receiving HAART who were subsequently diagnosed with ALS or an ALS-like disorder. Our goals were to describe our patients’ disease course and compare them to general characteristics of ALS. We report three cases of HIV-positive individuals, all male, who were subsequently diagnosed with ALS. Each presented with symptoms of limb onset ALS with involvement of upper and lower motor neurons and whose disease originated at the cervical level. All three had been diagnosed with HIV prior to presentation and were presumably compliant with antiretroviral therapy throughout. Our patients demonstrated effective control of their HIV infection. Each experienced relatively slow progression of motor impairment compared to general ALS characteristics. Our study offers a distinct profile of HIV-positive patients compliant with HAART subsequently diagnosed with an ALS-like disorder. Further study should aim to uncover pathophysiological similarities between motor neuron disease both in the presence and absence of retroviral infection and to develop effective medical therapy for each.

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Management challenges in patients with comorbid COVID-19 associated delirium and serious mental illness – A case series

The International Journal of Psychiatry in Medicine ◽

10.1177/0091217420985979 ◽

2021 ◽

pp. 009121742098597

Author(s):

Saba Syed ◽

Michael Couse ◽

Rashi Ojha

Keyword(s):

Mental Illness ◽

Serious Mental Illness ◽

Healthcare Providers ◽

Case Series ◽

Retrospective Chart Review ◽

Active Management ◽

The Novel ◽

Psychiatric Facility ◽

Medical Teams ◽

Novel Coronavirus

Background There is still a lot unknown about the novel Coronavirus Disease 19 (COVID-19) and its effects in humans. This pandemic has posed several challenging clinical situations to healthcare providers. Objective We hope to highlight the distinctive challenges that COVID-19 presents in patients with serious mental illness and what steps primary medical teams can take to co-manage these patients with the psychiatry consultants. Methods We present a retrospective chart review of four patients who were on psychotropic polypharmacy and admitted to our hospital from the same long-term psychiatric facility with COVID-19 delirium and other associated medical complications. Results We illustrate how the primary medical teams and psychiatrists collaborated in clinical diagnosis, treatment, and management. Conclusions Patients with serious mental illness and COVID-19 infection require active collaboration between primary medical teams and psychiatrists for diagnostic clarification, reduction of psychotropic polypharmacy to avoid adverse effects and drug-drug interactions, prevention of psychiatric decompensation, and active management of agitation while balancing staff and patient safety concerns.

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0897 Sleep Disordered Breathing In Pediatric Patients With Turner Syndrome

SLEEP ◽

10.1093/sleep/zsaa056.893 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A341-A342

Author(s):

Y A Yu ◽

B V Vaughn

Keyword(s):

Sleep Apnea ◽

Turner Syndrome ◽

Sleep Disordered Breathing ◽

Pediatric Patients ◽

Genetic Disorder ◽

Case Series ◽

Growth Failure ◽

Retrospective Chart Review ◽

Upper Airway Resistance Syndrome ◽

Disordered Breathing

Abstract Introduction Turner syndrome (TS) is a common genetic disorder that affects phenotypic females with partial or complete absence of one X chromosome. It typically presents with characteristic facial appearance, neck webbing, lymphedema, linear growth failure, and ovarian insufficiency. TS is also associated with other disorders, though sleep related disorders are not commonly reported. We present a case series of pediatric patients diagnosed with TS and assess their risk for sleep disordered breathing. Methods This study utilized retrospective chart review of the electronic medical record at the University of North Carolina at Chapel Hill from April 2014 to January 2019. Only pediatric patients under the age of 18 years who had previously undergone polysomnography and carrying the diagnosis of Turner syndrome were included in this study. Polysomnography results were reviewed. Results Retrospective chart analysis yielded ten (10) patients who qualified for inclusion. The mean age was 8.3 years (age range 1-15 years). Nine (9) patients were found to have sleep disordered breathing ranging from upper airway resistance syndrome to moderate sleep apnea (AHI range 1.2 to 6.2). Six (6) patients were found to have elevated periodic limb movement indices (PLM index range 5.1 to 30). Parasomnias and hypoventilation were not seen. Conclusion Our case series illustrates that sleep disordered breathing may be more common in TS than previously realized. Eklund et al. found that females with TS had more retrognathic mandibles and maxillas, shorter mandibles, and larger cranial base angles. These findings may indicate elevated risk of sleep apnea. Further studies are needed to define the overall risk of sleep disordered breathing in TS. Support None.

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Occipitocervicothoracic stabilization in pediatric patients

Journal of Neurosurgery Pediatrics ◽

10.3171/2011.4.peds10450 ◽

2011 ◽

Vol 8 (1) ◽

pp. 57-62 ◽

Cited By ~ 10

Author(s):

Kyle M. Fargen ◽

Richard C. E. Anderson ◽

David H. Harter ◽

Peter D. Angevine ◽

Valerie C. Coon ◽

...

Keyword(s):

Cervical Spine ◽

Thoracic Spine ◽

Pediatric Patients ◽

Pathological Condition ◽

Case Series ◽

Neurological Function ◽

Spinal Reconstruction ◽

Spine Deformities ◽

Distal Fixation

Object Although rarely encountered, pediatric patients with severe cervical spine deformities and instability may occasionally require occipitocervicothoracic instrumentation and fusion. This case series reports the experience of 4 pediatric centers in managing this condition. Occipitocervical fixation is the treatment of choice for craniocervical instability that is symptomatic or threatens neurological function. In children, the most common distal fixation level with modern techniques is C-2. Treated patients maintain a significant amount of neck motion due to the flexibility of the subaxial cervical spine. Distal fixation to the thoracic spine has been reported in adult case series. This procedure is to be avoided due to the morbidity of complete loss of head and neck motion. Unfortunately, in rare cases, the pathological condition or highly aberrant anatomy may require occipitocervical constructs to include the thoracic spine. Methods The authors identified 13 patients who underwent occipitocervicothoracic fixation. Demographic, radiological, and clinical data were gathered through retrospective review of patient records from 4 institutions. Results Patients ranged from 1 to 14 years of age. There were 7 girls and 6 boys. Diagnoses included Klippel-Feil, Larsen, Morquio, and VATER syndromes as well as postlaminectomy kyphosis and severe skeletal dysplasia. Four patients were neurologically intact and 9 had myelopathy. Five children were treated with preoperative traction prior to instrumentation; 5 underwent both anterior and posterior spinal reconstruction. Two patients underwent instrumentation beyond the thoracic spine. Allograft was used anteriorly, and autologous rib grafts were used in the majority for posterior arthrodesis. Follow-up ranged from 0 to 43 months. Computed tomography confirmed fusion in 9 patients; the remaining patients were lost to follow-up or had not undergone repeat imaging at the time of writing. Patients with myelopathy either improved or stabilized. One child had mild postoperative unilateral upper-extremity weakness, and a second child died due to a tracheostomy infection. All patients had severe movement restriction as expected. Conclusions Occipitocervicothoracic stabilization may be employed to stabilize and reconstruct complex pediatric spinal deformities. Neurological function can be maintained or improved. The long-term morbidity of loss of cervical motion remains to be elucidated.

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A Case Series of the Use of Piezosurgery Instrument for Minimally Invasive Metopic Suturectomy

Operative Neurosurgery ◽

10.1093/ons/opab006 ◽

2021 ◽

Author(s):

Ben G McGahan ◽

Joravar Dhaliwal ◽

Gregory D Pearson ◽

Ibrahim Khansa ◽

Annie I Drapeau

Keyword(s):

Case Series ◽

Retrospective Chart Review ◽

Minimal Invasive ◽

Surgical Approaches ◽

Average Weight ◽

Entire Cohort ◽

Metopic Suture ◽

The Many ◽

Single Suture ◽

Metopic Craniosynostosis

Abstract BACKGROUND Minimal invasive suturectomy is one of the many surgical approaches to treat isolated single suture craniosynostosis. This approach can be technically challenging in metopic craniosynostosis given the narrow corridor and steep angle of the forehead. New instruments such as the Piezosurgery device (Mectron) have the potential to improve the ability to safely perform minimal invasive surgery in metopic craniosynostosis. OBJECTIVE To demonstrate the safety and efficacy of Piezosurgery technology in minimal invasive suturectomy for nonsyndromic metopic suture craniosynostosis and to describe our technique. METHODS A retrospective chart review was performed of all the single metopic suturectomies performed at our single institution from March 2018 to November 2019. Pre-, intra-, and postoperative data were collected to assess the safety of Piezosurgery. RESULTS The cohort consisted of 12 patients with an average of 95.25 d old and an average weight of 6.2 kg. A total of 91.7% were male, and 91.7% were Caucasian. There were no intraoperative or postoperative Piezosurgery device-related complications in the entire cohort. CONCLUSION The use of the Piezosurgery instrument was safe in this cohort of minimal invasive metopic suturectomy. This device has greatly increased the ease of this procedure in our hands.

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