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Journal of Medical Genetics Mar 2017In 1993, Chitayat , reported a newborn with hyperphalangism, facial anomalies, and bronchomalacia. We identified three additional families with similar findings....
BACKGROUND
In 1993, Chitayat , reported a newborn with hyperphalangism, facial anomalies, and bronchomalacia. We identified three additional families with similar findings. Features include bilateral accessory phalanx resulting in shortened index fingers; hallux valgus; distinctive face; respiratory compromise.
OBJECTIVES
To identify the genetic aetiology of Chitayat syndrome and identify a unifying cause for this specific form of hyperphalangism.
METHODS
Through ongoing collaboration, we had collected patients with strikingly-similar phenotype. Trio-based exome sequencing was first performed in Patient 2 through Deciphering Developmental Disorders study. Proband-only exome sequencing had previously been independently performed in Patient 4. Following identification of a candidate gene variant in Patient 2, the same variant was subsequently confirmed from exome data in Patient 4. Sanger sequencing was used to validate this variant in Patients 1, 3; confirm paternal inheritance in Patient 5.
RESULTS
A recurrent, novel variant NM_006494.2:c.266A>G p.(Tyr89Cys) in was identified in five affected individuals: de novo (patient 1, 2 and 3) and inherited from an affected father (patient 4 and 5). p.Tyr89Cys is an aromatic polar neutral to polar neutral amino acid substitution, at a highly conserved position and lies within the functionally important ETS-domain of the protein. The recurrent c.266A>C p.(Tyr89Cys) variant causes Chitayat syndrome.
DISCUSSION
variants have previously been associated with complex craniosynostosis. In contrast, none of the patients with the c.266A>G p.(Tyr89Cys) variant have craniosynostosis.
CONCLUSIONS
We report the molecular aetiology of Chitayat syndrome and discuss potential mechanisms for this distinctive phenotype associated with the p.Tyr89Cys substitution in .
Topics: Abnormalities, Multiple; Bronchomalacia; Dandy-Walker Syndrome; Developmental Disabilities; Exome; Face; Facial Bones; Female; Hallux Valgus; High-Throughput Nucleotide Sequencing; Humans; Infant, Newborn; Male; Phenotype; Repressor Proteins
PubMed: 27738187
DOI: 10.1136/jmedgenet-2016-104143 -
Respiratory Care Feb 2015Pompe disease is a rare autosomal recessive disorder caused by α-glucosidase deficiency. Lower airway involvement and management are rare in patients with late-onset...
Pompe disease is a rare autosomal recessive disorder caused by α-glucosidase deficiency. Lower airway involvement and management are rare in patients with late-onset Pompe disease. We describe the case of a 16-y-old girl with late-onset Pompe disease who presented with obvious progressive deterioration in respiratory function. Pulmonary hypertension was also apparent on echocardiography. She had been on enzyme replacement therapy and nighttime CPAP ventilation for several years. Flexible bronchoscopy was used for diagnosis and subsequent implantation of a bronchial airway stent. Following implantation of the stent, the patient's pulmonary function stabilized, and her pulmonary hypertension resolved. The patient continued on enzyme replacement therapy and nighttime CPAP ventilation. This case highlights that lower airway involvement may occur with late-onset Pompe disease and that flexible bronchoscopy can be an effective tool for both diagnosis and management of lower airway collapse in late-onset Pompe disease.
Topics: Adolescent; Bronchomalacia; Bronchoscopy; Continuous Positive Airway Pressure; Female; Glycogen Storage Disease Type II; Humans; Sleep Apnea, Obstructive; Stents
PubMed: 25316892
DOI: 10.4187/respcare.03419 -
The Journal of Thoracic and... May 2019
Topics: Bronchomalacia; Cardiac Surgical Procedures; Child; Humans; Polyesters; Printing, Three-Dimensional
PubMed: 30711283
DOI: 10.1016/j.jtcvs.2018.12.088 -
Otolaryngology--head and Neck Surgery :... Feb 2020
Review
Topics: Abnormalities, Multiple; Bronchomalacia; Ethics, Medical; Heart Defects, Congenital; Humans; Infant; Informed Consent; Male; Otorhinolaryngologic Surgical Procedures; Printing, Three-Dimensional; Tracheomalacia
PubMed: 31874066
DOI: 10.1177/0194599819897067 -
BMJ Case Reports Apr 2022A woman in her late 80s with severe bronchomalacia was referred to a tertiary orofacial pain clinic for unexplained right unilateral glossodynia of progressive and...
A woman in her late 80s with severe bronchomalacia was referred to a tertiary orofacial pain clinic for unexplained right unilateral glossodynia of progressive and continuous evolution for the past 8 months, spreading to the ipsilateral labiomental region, associated with ipsilateral hypoacusia. Local and general clinical examinations were unremarkable and routine blood work could not reveal any underlying systemic disease explaining the glossodynia and burning/pricking labiomental pain. Suspecting a painful trigeminal neuropathy secondary to a space-occupying lesion, a cerebral MRI was prescribed, revealing an ipsilateral cerebellopontine angle lesion, compatible with either a schwannoma or meningioma. This lesion invaded the root entry zones of cranial nerves V and VIII explaining the patient's oral pain and hypoacusia. Following a neurosurgical consultation where surgical treatment was rejected, her pain was successfully managed by topical pregabalin mouthwashes, to prevent any risk of respiratory depression related to her underlying severe bronchomalacia.
Topics: Bronchomalacia; Cerebellopontine Angle; Female; Glossalgia; Humans; Meningeal Neoplasms; Neuroma, Acoustic
PubMed: 35414584
DOI: 10.1136/bcr-2022-249408 -
American Journal of Respiratory and... Jun 2020: Bronchopulmonary dysplasia (BPD) is a heterogenous condition with poorly characterized disease subgroups.: To define the frequency of three disease components:...
: Bronchopulmonary dysplasia (BPD) is a heterogenous condition with poorly characterized disease subgroups.: To define the frequency of three disease components: moderate-severe parenchymal disease, pulmonary hypertension (PH), or large airway disease, in a referral cohort of preterm infants with severe BPD. The association between each component and a primary composite outcome of death before hospital discharge, tracheostomy, or home pulmonary vasodilator therapy was assessed.: This was a retrospective, single-center cohort study of infants born at <32 weeks' gestation with severe BPD who underwent both chest computed tomography with angiography (CTA) and echocardiography between 40 and 50 weeks postmenstrual age between 2011 and 2015. Moderate-severe parenchymal lung disease was defined as an Ochiai score ≥8 on CTA. PH was diagnosed by echocardiogram using standard criteria. Large airway disease was defined as tracheomalacia or bronchomalacia on bronchoscopy and/or tracheoscopy or CTA.: Of 76 evaluated infants, 73 (96%) were classifiable into phenotypic subgroups: 57 with moderate-severe parenchymal disease, 48 with PH, and 44 with large airway disease. The presence of all three disease components was most common ( = 23). Individually, PH and large airway disease, but not moderate-severe parenchymal disease, were associated with increased risk for the primary study outcome. Having more disease components was associated with an incremental increase in the risk for the primary outcome (2 vs. 1: odds ratio, 4.9; 95% confidence interval, 1.4-17.2 and 3 vs. 1: odds ratio, 12.8; 95% confidence interval, 2.4-70.0).: Infants with severe BPD are variable in their predominant pathophysiology. Disease phenotyping may enable better risk stratification and targeted therapeutic intervention.
Topics: Bronchopulmonary Dysplasia; Cohort Studies; Female; Humans; Infant, Newborn; Infant, Premature; Male; Phenotype; Retrospective Studies; Severity of Illness Index
PubMed: 31995403
DOI: 10.1164/rccm.201907-1342OC -
The Laryngoscope Feb 2023Standard methods to evaluate tracheal pathology in children, including bronchoscopy, may require general anesthesia. Conventional dynamic proximal airway imaging in...
OBJECTIVE
Standard methods to evaluate tracheal pathology in children, including bronchoscopy, may require general anesthesia. Conventional dynamic proximal airway imaging in noncooperative children requires endotracheal intubation and/or medically induced apnea, which may affect airway mechanics and diagnostic performance. We describe a technique for unsedated dynamic volumetric computed tomography angiography (DV-CTA) of the proximal airway and surrounding vasculature in children and evaluate its performance compared to the reference-standard of rigid bronchoscopy.
METHODS
Children who had undergone DV-CTA and bronchoscopy in one-year were retrospectively identified. Imaging studies were reviewed by an expert reader blinded to the bronchoscopy findings of primary or secondary tracheomalacia. Airway narrowing, if present, was characterized as static and/or dynamic, with tracheomalacia defined as >50% collapse of the tracheal cross-sectional area in exhalation. Pearson correlation was used for comparison.
RESULTS
Over a 19-month period, we identified 32 children (median age 8 months, range 3-14 months) who had undergone DV-CTA and bronchoscopy within a 90-day period of each other. All studies were unsedated and free-breathing. The primary reasons for evaluation included noisy breathing, stridor, and screening for tracheomalacia. There was excellent agreement between DV-CTA and bronchoscopy for diagnosis of tracheomalacia (κ = 0.81, p < 0.001), which improved if children (n = 25) had the studies within 30 days of each other (κ = 0.91, p < 0.001). CTA provided incremental information on severity, and cause of secondary tracheomalacia.
CONCLUSION
For most children, DV-CTA requires no sedation or respiratory manipulation and correlates strongly with bronchoscopy for the diagnosis of tracheomalacia.
LEVEL OF EVIDENCE
3 Laryngoscope, 133:410-416, 2023.
Topics: Humans; Child; Infant, Newborn; Tracheomalacia; Computed Tomography Angiography; Retrospective Studies; Tomography, X-Ray Computed; Trachea; Bronchoscopy
PubMed: 35411953
DOI: 10.1002/lary.30125 -
Journal of Veterinary Internal Medicine May 2019Bronchoalveolar lavage (BAL) fluid cytology and culture are used to characterize respiratory diseases in dogs. Little is known about disorders associated with increased...
BACKGROUND
Bronchoalveolar lavage (BAL) fluid cytology and culture are used to characterize respiratory diseases in dogs. Little is known about disorders associated with increased numbers of lymphocytes in BAL fluid.
OBJECTIVE
To evaluate duration of clinical signs and detection of specific respiratory diagnoses in dogs with BAL lymphocytosis.
ANIMALS
One-hundred four client-owned dogs evaluated for respiratory signs.
METHODS
Medical records of dogs that had >300 cells/μL and >20% lymphocytes on a differential cell count of BAL fluid between January 1, 2006, and January 1, 2016, were reviewed retrospectively. Cases were evaluated for the duration of clinical signs and respiratory diagnoses, including aspiration injury, infectious or inflammatory respiratory disease, and airway collapse.
RESULTS
Dogs ranged in age from 0.5 to 16 years (median, 7.9 years) and had a median body weight of 11.4 kg (range, 2.0-42.7 kg). Eosinophilic lung disease was documented in 13 of 104 dogs (Group 1) and airway neutrophilia associated with infectious or inflammatory disease was found in 59 of 104 dogs (Group 2). Lymphocytosis alone in BAL fluid was described in 32 dogs (Group 3). Duration of cough did not differ among groups, but airway collapse was significantly more common in dogs with solitary lymphocytosis than in those with other types of inflammation.
CONCLUSIONS AND CLINICAL IMPORTANCE
Lymphocytosis in BAL fluid is common in dogs and, in many cases, likely represents a common response to airway injury, independent of the type or duration of insult. It is unknown whether airway collapse leads to lymphocytosis or if the inflammatory process causes airway collapse.
Topics: Airway Obstruction; Animals; Bronchoalveolar Lavage Fluid; Cough; Dog Diseases; Dogs; Female; Inflammation; Male; Neutrophils; Pulmonary Eosinophilia; Respiratory Aspiration; Respiratory Tract Diseases; Retrospective Studies
PubMed: 30912207
DOI: 10.1111/jvim.15489 -
BMC Pulmonary Medicine Apr 2023Relapsing polychondritis (RP) is a chronic and recurrent inflammatory disease of the cartilage tissues in the body. The cause of RP is unknown, and since it is a rare...
BACKGROUND
Relapsing polychondritis (RP) is a chronic and recurrent inflammatory disease of the cartilage tissues in the body. The cause of RP is unknown, and since it is a rare disease with symptoms that affect multiple organs, diagnosis is often delayed.
CASE PRESENTATION
A 62-year-old woman with no smoking history visited our institution complaining of fever, cough, and dyspnoea. Chest CT showed a stenosis from the left main bronchus to the left lower lobe branch. Bronchoscopy visualised intense erythema and oedema at the left main bronchus, with airway narrowing. Biopsy of the ear revealed degenerative vitreous cartilage and fibrous connective tissue with a mild inflammatory cell infiltrate. She was subsequently diagnosed with RP and administered systemic corticosteroid therapy. Her symptoms improved rapidly, and post-treatment bronchoscopy revealed that although mild erythema of the airway epithelium remained, oedema markedly improved, and the airway stenosis was resolved.
CONCLUSIONS
We report a case where pre-treatment bronchoscopy was able to visually confirm RP at the acute stage. Since RP is difficult to diagnose, severe airway narrowing can occur prior to diagnosis. Therefore, to determine the stage of the disease, it is helpful to perform bronchoscopic observation before treatment. However, bronchoscopic observation before treatment should be performed by experienced bronchoscopists due to the risk of airway obstruction.
Topics: Humans; Female; Middle Aged; Constriction, Pathologic; Trachea; Airway Obstruction; Lung; Dyspnea; Polychondritis, Relapsing
PubMed: 37013530
DOI: 10.1186/s12890-023-02400-z -
BMJ Case Reports Feb 2021We reported here a boy aged 5 years who presented for the evaluation of recurrent croup since infancy. On chest examination, breath sounds were reduced throughout the...
We reported here a boy aged 5 years who presented for the evaluation of recurrent croup since infancy. On chest examination, breath sounds were reduced throughout the right lung field with a shifting of the trachea and cardiac apex to the right side. The chest radiograph showed a small right lung with decreased vascularity, hyperinflated left lung and mediastinum shifted towards the right side. Flexible bronchoscopy revealed tracheomalacia with left bronchomalacia due to external pulsatile compression. In CT angiogram, the right pulmonary artery (PA) was absent with dilated left PA. Echocardiography did not show any features of pulmonary arterial hypertension (PAH). Since the child was growing well, and there was no limitation of activity and evidence of PAH, he was managed conservatively and kept on follow-up. Though unilateral absent PA is a rare condition, it should be suspected in children with unilateral hypoplastic lung.
Topics: Bronchomalacia; Bronchoscopy; Child; Child, Preschool; Croup; Humans; Male; Pulmonary Artery; Respiratory System Abnormalities
PubMed: 33619150
DOI: 10.1136/bcr-2020-236605