Chromothripsis: Basis of a Concurrent Unusual Association between Myelodysplastic Syndrome and Primary Ciliary Dyskinesia

A 20 year old male was initially diagnosed suffering from Primary ciliary dyskinesia with symptoms of bronchiectasis, severe frontal, maxillary and ethmoid sinus disease. At the age of 20, the patient was also diagnosed with Myelodysplastic syndrome requiring Bone marrow transplant due to the advanced stage at time of presentation. Primary ciliary dyskinesia and Myelodsyplastic syndrome are both rare clinical conditions found in the general population, especially in young adults. This rare combination of disorders has never been reported in literature to the best of the author’s knowledge. The presence of an advanced cancer and a genetic abnormality due to two deletions occurring in two arms of the same chromosome can be explained on the base of chromothripsis. A number of evidences have been published in the literature, about multiple deletions in chromosome 5 and advanced stages of MDS being associated with chromothripsis however this is the first case report on two deletions in chromosome 7 giving rise to two different clinical entities requiring multiple modes of management.

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Extended Interval Tobramycin Pharmacokinetics in a Pediatric Patient With Primary Ciliary Dyskinesia Presenting With an Acute Respiratory Exacerbation

The Journal of Pediatric Pharmacology and Therapeutics ◽

10.5863/1551-6776-23.2.159 ◽

2018 ◽

Vol 23 (2) ◽

pp. 159-163

Author(s):

Kristi L. Higgins ◽

Cady Noda ◽

Jeremy S. Stultz

Keyword(s):

Cystic Fibrosis ◽

Primary Ciliary Dyskinesia ◽

Elimination Rate ◽

Area Under The Curve ◽

Volume Of Distribution ◽

Treatment Recommendation ◽

Pharmacokinetic Parameters ◽

Maximum Serum ◽

First Case ◽

Ciliary Dyskinesia

The pharmacokinetics of tobramycin in patients with ciliary dyskinesia have not been previously reported. A 10-year-old female patient with primary ciliary dyskinesia was admitted to the general pediatrics floor with an acute respiratory exacerbation after several months of worsening lung function that was unresponsive to oral antibiotics. Extrapolating from cystic fibrosis dosing regimens, she was given intravenous tobramycin 320 mg (10.3 mg/kg/day) on admission as a result of concern for a Pseudomonas aeruginosa infection. Two-point pharmacokinetic monitoring revealed a maximum serum concentration (Cmax) of 18.9 mg/L and a 24-hour area under the curve (AUC0–24hr) of 58.8 (mg × hr)/L, as well as a volume of distribution (Vd) of 0.5 L/kg and an elimination rate (Ke) of 0.34 hr−1. After a dosage increase to tobramycin 400 mg (12.8 mg/kg/day), pharmacokinetic parameters on 2 assessments were as follows: Vd 0.37 to 0.39 L/kg, Ke 0.33 to 0.39 hr−1, Cmax 27.8 to 28.7 mg/L, and AUC0–24h 78.4 to 89.4 (mg × hr)/L. This was the first case report of aminoglycoside pharmacokinetics in a patient with ciliary dyskinesia. The administration of larger doses (up to 12.8 mg/kg/day) of extended-interval tobramycin, similar to the treatment recommendation of at least 10 mg/kg/day for cystic fibrosis patients, was necessary in this patient to achieve serum concentrations that were appropriate for treatment.

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Olfactory dysfunction is worse in primary ciliary dyskinesia compared with other causes of chronic sinusitis in children

Thorax ◽

10.1136/thoraxjnl-2017-210661 ◽

2018 ◽

Vol 73 (10) ◽

pp. 980-982 ◽

Cited By ~ 3

Author(s):

Massimo Pifferi ◽

Andrew Bush ◽

Michele Rizzo ◽

Alessandro Tonacci ◽

Maria Di Cicco ◽

...

Keyword(s):

Electron Microscopy ◽

Primary Ciliary Dyskinesia ◽

Chronic Sinusitis ◽

Olfactory Dysfunction ◽

Healthy Controls ◽

Sinus Disease ◽

Multiple Functions ◽

Nasal Nitric Oxide ◽

Transmission Electron ◽

Ciliary Dyskinesia

Cilia have multiple functions including olfaction. We hypothesised that olfactory function could be impaired in primary ciliary dyskinesia (PCD). Olfaction, nasal nitric oxide (nNO) and sinus CT were assessed in patients with PCD and non-PCD sinus disease, and healthy controls (no CT scan). PCD and non-PCD patients had similar severity of sinus disease. Despite this, defective olfaction was more common in patients with PCD (P<0.0001) and more severe in patients with PCD with major Transmission Electron Microscopy (TEM) abnormalities. Only in classical PCD did olfaction inversely correlate with sinusitis and nNO. We speculate that defective olfaction in PCD is primary in nature.

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Primary ciliary dyskinesia in a Staffordshire bull terrier : clinical communication

Journal of the South African Veterinary Association ◽

10.4102/jsava.v75i3.471 ◽

2004 ◽

Vol 75 (3) ◽

Cited By ~ 5

Author(s):

M. De Scally ◽

R.G. Lobetti ◽

E. Van Wilpe

Keyword(s):

Cross Sections ◽

Primary Ciliary Dyskinesia ◽

Clinical Communication ◽

First Case ◽

Transmission Electron ◽

Radial Spokes ◽

History Of ◽

Tract Infections ◽

Ciliary Dyskinesia ◽

Recurrent Respiratory Tract Infections

Primary ciliary dyskinesia (PCD) is a diverse group of inherited structural and functional abnormalities of the respiratory and other cilia, which results in recurrent respiratory tract infections. Primary ciliary dyskinesia was diagnosed in a 14-week old Staffordshire bull terrier that had a history of respiratory disease from 7 weeks of age. Pneumonia was diagnosed on thoracic radiographs and transtracheal aspirate. Transmission electron microscopy of the bronchi and trachea indicated the presence of both primary and secondary ciliary dyskinesia. The most prominent primary defects consisted of absent inner dyneim arms, absent radial spokes and absence of the central microtubules. These defects accounted for 62 % of the total number of cross-sections screened. Non-specific ciliary abnormalities encountered most often were compound cilia, swollen cilia, addition / deletion of peripheral doublets and disorganised axonemes (26 %). To the authors' knowledge, this is the first case of PCD described in the Staffordshire bull terrier and the first report of PCD in South Africa.

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Rhinosinusitis in Pediatric Primary Ciliary Dyskinesia: Impact of Disease

Otolaryngology ◽

10.1177/0194599819874842 ◽

2019 ◽

Vol 161 (5) ◽

pp. 877-880 ◽

Cited By ~ 2

Author(s):

Jay M. Bhatt ◽

Ethan G. Muhonen ◽

Maxene Meier ◽

Scott D. Sagel ◽

Kenny H. Chan

Keyword(s):

Primary Ciliary Dyskinesia ◽

Genetic Disorder ◽

Retrospective Chart Review ◽

Sinus Surgery ◽

Record System ◽

Sinus Disease ◽

Respiratory Cilia ◽

Genetic Test Results ◽

Biallelic Mutations ◽

Ciliary Dyskinesia

Objectives Primary ciliary dyskinesia (PCD) is a genetic disorder characterized by abnormal respiratory cilia ultrastructure and/or function causing defective mucociliary clearance. We investigated the extent and severity of rhinosinusitis in a large cohort of children with PCD and explored associations among risk factors, including genotype and sinus disease. Study Design Retrospective chart review. Setting Tertiary academic children’s hospital. Subjects and Methods A review was conducted with a patient registry at the PCD Foundation Center at our institution. Demographic, imaging, clinical, and operative data were reviewed through the institutional electronic health record system. Results Fifty-four subjects were identified with mean and median age at diagnosis of 5.2 and 4.0 years. The male:female ratio was 35%:65%. Sinus symptoms were present in 46 (85%) subjects, 22 of whom had chronic rhinosinusitis. Nineteen (35%) subjects underwent operative intervention, consisting of endoscopic sinus surgery (ESS; 16 patients) and maxillary lavage (3 patients). Nineteen subjects underwent adenoidectomy for PCD-related indications. Five sinus-related admissions in 3 subjects were noted during the study period, and no complication of rhinosinusitis occurred in the cohort. Genetic test results were available in 27 subjects, in whom 23 (85%) had biallelic mutations in a PCD gene. Demographic factors, Lund-Mackay score, and PCD genotype were not found to be predictors for ESS or hospitalization in our cohort. Conclusion While rhinosinusitis was common in our PCD cohort, most patients did not require ESS. Since complications of rhinosinusitis were uncommon, we recommend judicious surgical management tailored to the patient’s symptoms.

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