Situs Inversus Totalis in a Newborn With Primary Ciliary Dyskinesia.

Respiratory distress in the newborn is associated with numerous etiologies, some common and some rare. When respiratory distress is accompanied by laterality defects, namely, situs inversus (SI), the index of suspicion for comorbid primary ciliary dyskinesia (PCD) should be raised. Primary ciliary dyskinesia is characterized by ciliary dysmotility and the accumulation of thick secretions in the airways that obstruct air and gas exchange. Neonatal clinicians should know that while PCD is definitively diagnosed in infancy or early childhood, findings suspicious for PCD should be communicated to primary care providers at discharge from the hospital to facilitate timely subspecialty involvement, diagnosis, and treatment. This article will present a case report of a term newborn with SI totalis who was later diagnosed with PCD. We will discuss epidemiology, pathophysiology, clinical manifestations, and diagnostics, followed by management strategies. Additionally, we discuss the outpatient needs and lifespan implications.

[Primary ciliary dyskinesia]. / Primäre Ciliäre Dyskinesie.

Primary ciliary dyskinesia (PCD) is a rare genetic disorder with a variable clinical phenotype that is accompanied by reduced motility of the cilia in the respiratory tract and numerous other organs. This leads to various characteristic symptoms and disease manifestations, primarily affecting the lungs (chronic persistent productive cough, bronchiectasis), the nose and paranasal sinuses (chronic persistent rhinitis or rhinosinusitis) as well as the middle ear (chronic otitis media, middle ear effusion). Moreover, PCD is associated with impaired fertility or lateralization defects (situs anomalies, congenital heart defects). The diagnostics of PCD are complex and require a combination of several sophisticated instrument-based diagnostic procedures. Through thorough history taking and evaluation, suspected cases can be comparatively well identified based on typical clinical features and referred to further diagnostics. In recent years, molecular genetic analysis through panel diagnostics or whole exome and whole genome sequencing, has gained in importance as this enables affected individuals to participate in disease-specific and genotype-specific clinical trials. Although the current treatment is purely symptomatic, the earliest possible diagnosis is crucial for connecting patients to specialized PCD centers, which can have a significant impact on the clinical course of the affected individuals.

Primary Ciliary Dyskinesia.

Primary ciliary dyskinesia (PCD) is a rare, genetic disease characterized by dysfunctional motile cilia and abnormal mucociliary clearance, resulting in chronic sino-oto-pulmonary disease, neonatal respiratory distress, subfertility, and organ laterality defects. Over the past 2 decades, research and international collaborations have led to an improved understanding of disease prevalence, classic and variable phenotypes, novel diagnostics, genotype-phenotype correlations, long term morbidity, and innovative therapeutics. However, PCD is often underrecognized in clinical settings and the recent analyses of genetic databases suggest that only a fraction of these patients are being accurately diagnosed. Knowledge of significant advancements, from pathophysiology to the expanded range of clinical manifestations, will have important clinical impacts. These may include increasing disease recognition, improving diagnostic testing and management, and establishing an adequate pool of affected patients to enroll in upcoming clinical therapeutic trials. The objective of this state-of-the-art review is for readers to gain a greater understanding of the clinical spectrum of motile ciliopathies, cutting-edge diagnostic practices, emerging genotype-phenotype associations, and currently accepted management of people with PCD.

Practical guide for the diagnosis and management of primary ciliary dyskinesia.

OBJECTIVE: Primary ciliary dyskinesia (PCD) is a relatively rare genetic disorder that affects approximately 1 in 20,000 people. Approximately 50 genes are currently known to cause PCD. In light of differences in causative genes and the medical system in Japan compared with other countries, a practical guide was needed for the diagnosis and management of Japanese PCD patients. METHODS: An ad hoc academic committee was organized under the Japanese Rhinologic Society to produce a practical guide, with participation by committee members from several academic societies in Japan. The practical guide including diagnostic criteria for PCD was approved by the Japanese Rhinologic Society, Japanese Society of Otolaryngology-Head and Neck Surgery, Japanese Respiratory Society, and Japanese Society of Pediatric Pulmonology. RESULTS: The diagnostic criteria for PCD consist of six clinical features, six laboratory findings, differential diagnosis, and genetic testing. The diagnosis of PCD is categorized as definite, probable, or possible PCD based on a combination of the four items above. Diagnosis of definite PCD requires exclusion of cystic fibrosis and primary immunodeficiency, at least one of the six clinical features, and a positive result for at least one of the following: (1) Class 1 defect on electron microscopy of cilia, (2) pathogenic or likely pathogenic variants in a PCD-related gene, or (3) impairment of ciliary motility that can be repaired by correcting the causative gene variants in iPS cells established from the patient's peripheral blood cells. CONCLUSION: This practical guide provides clinicians with useful information for the diagnosis and management of PCD in Japan.

Fertility care among people with primary ciliary dyskinesia.

INTRODUCTION: Fertility care is important for people living with primary ciliary dyskinesia (PCD) who are at increased risk of fertility problems. We investigated fertility care in an international participatory study. METHODS: Participants of the COVID-PCD study completed an online questionnaire addressing fertility issues. We used logistic regression to study factors associated with fertility specialist visits. RESULTS: Among 384 respondents (response rate 53%), 266 were adults (median age 44 years, interquartile range [IQR]: 33-54, 68% female), 16 adolescents, and 102 parents of children with PCD. Only half of adult participants (128; 48%) received care from fertility specialists at a median age of 30 years (IQR: 27-33)-a median of 10 years after PCD diagnosis. Only 12% were referred to fertility specialists by their PCD physician. Fertility specialist visits were reported more often by adults with pregnancy attempts (odds ratio [OR]: 9.1, 95% confidence interval [CI]: 3.8-23.6) and among people who reported fertility as important for them (OR: 5.9, 95% CI: 2.6-14.6) and less often by females (OR: 0.4, 95% CI: 0.2-0.8). Only 56% of participants who talked with healthcare professionals about fertility were satisfied with information they received. They expressed needs for more comprehensive fertility information and reported dissatisfaction with physician knowledge about PCD and fertility. CONCLUSION: People with PCD are inconsistently referred to fertility specialists. We recommend care from fertility specialists become standard in routine PCD care, and that PCD physicians provide initial fertility information either at diagnosis or no later than transition to adult care.

Successful ART outcome with donor oocytes in female Kartagener's syndrome: a case report and follow-up.

A 30-year-old woman presented with history of primary infertility of 8 years and multiple failed intrauterine insemination (IUI) attempts. She had the classic symptoms of Kartagener's syndrome-situs inversus, chronic sinusitis, and bronchiectasis. She had polycystic ovarian disease (PCOD) with regular menstrual cycles. Her karyotyping was normal. There was no other significant history including surgeries and the marriage was non-consanguineous. Her partner was 34 years old with normal semen and hormonal parameters. Her first intra-cytoplasmic sperm injection (ICSI) cycle with her own oocytes and husband's sperm resulted in a pregnancy but she suffered a miscarriage at 11 weeks. Her second attempt with donor oocytes and husband's sperm resulted in a pregnancy again but she miscarried at 9 weeks. The third attempt with a frozen embryo transfer with supernumerary embryos resulted in a pregnancy and she delivered a live female baby who was followed up for 8 years. This is the first report of a patient with KS undergoing assisted reproduction technologies (ART) treatment with donor oocytes. This is also the first Indian report of a female KS patient undergoing ART treatment with donor oocytes. IUI may not be the ideal treatment option in female patients with KS.

Primary ciliary dyskinesia: A multicenter survey on clinical practice and patient management in Italy.

INTRODUCTION: There are no recent data on primary ciliary dyskinesia (PCD) distribution, diagnosis and treatment in Italy. METHODS: A descriptive study based on a survey questionnaire. It consisted of three sections (patients, diagnosis, and treatment), and sent to all the Italian PCD Centers. RESULTS: Questionnaires obtained from 20/22 centers in 12/20 regions showed that the total number of PCD patients treated at the participating centers was of 416. Out of all centers, 55% follow <20 patients, two centers have >40 patients, and 75% follow both pediatric and adults. Age at diagnosis was between 4 and 8 years in 45% of the centers, <3 years in three centers. Nasal nitric oxide, transmission electron microscopy and ciliary high-speed video microscopy are performed in 75%, 90%, and 40% of centers, respectively. Immunofluorescence is available in five centers. Genetic analysis is offered in 55% of the centers, and in seven centers >50% of the patients have a known genetic profile. Patients treated at all centers receive inhaled saline solutions, corticosteroids and chest physiotherapy. Prophylactic antibiotics and mucolytics are prescribed in 95% and 50% of the centers, respectively. Pseudomonas infection is treated with oral or inhaled antibiotics. CONCLUSIONS: Many Italian centers care for a small number of pediatric and adult patients, and diagnosis is often delayed. We found a great variability in the available diagnostic procedures, as well in the prescribed therapies. Our study will help to uniform diagnostic algorithm and share treatments protocols for PCD in Italy and allowed to set specific national goals.

Active video gaming in primary ciliary dyskinesia: a randomized controlled trial.

Primary ciliary dyskinesia (PCD) impairs pulmonary function, respiratory and peripheral muscle strength, and exercise capacity. We aimed to investigate the effects of active video games (AVGs) on pulmonary function, respiratory and peripheral muscle strength, exercise capacity, muscle oxygenation (SMO2), physical activity, activities of daily living (ADL), and quality of life (QOL) in PCD. Thirty-two PCD patients were randomly assigned to AVG group (n = 16) and the control group (n = 16). AVG group underwent AVGs using Xbox-Kinect-360 device for 40 min/day, 3 days/week for 8 weeks plus airway clearance techniques (ACT), and the control group was applied ACT only. Pulmonary function, respiratory and quadriceps muscle strength, exercise capacity (6-min walk test [6MWT], incremental shuttle walk test [ISWT]), and ADL (Glittre ADL test) were assessed. SMO2 during ISWT and ADL test was also recorded. Physical activity and QOL (PCD-QOL) were evaluated. Pulmonary function; respiratory and quadriceps muscle strength; 6MWT and ISWT distance; physical activity; ADL performance; SMO2; physical, emotional, and social functioning; treatment burden; and upper and lower symptom parameters of PCD-QOL significantly improved after 8 weeks in the AVG group (p < 0.05). There were no significant differences in measured parameters except emotional function and upper respiratory symptom scores of PCD-QOL in the control group (p > 0.05).    Conclusion: The AVGs positively affect pulmonary (pulmonary function, respiratory muscle strength) and extrapulmonary (peripheral muscle strength, exercise capacity, SMO2, physical activity, ADL, and QOL) characteristics in children with PCD. The AVGs may be added to the pulmonary rehabilitation program as an exercise training modality in patients with PCD.   Trial registration: This study registered at ClinicalTrials.gov with NCT03832491 on February 6, 2019. What is Known: • It is indicated that exercise capacity is increased with traditional exercise-training in a case report of Kartagener Syndrome. What is New: • No randomized controlled study investigated the effects of exercise-training in PCD. • 8-week moderate-intensity active video gaming (AVGs) improves pulmonary and extrapulmonary features in children with PCD. AVGs may be preferable due to being enjoyable, providing visual and audial feedback in the pulmonary rehabilitation programs of PCD.

Primary Ciliary Dyskinesia: A Rare and Often Underdiagnosed Disease.

Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disease with clinical features of ear, sinus, and pulmonary infections that overlap with common respiratory illnesses of childhood. It is a progressive disorder that has significant influence on quality of life, lung function, and survival. Given the considerable overlap of symptoms between common illnesses and PCD, a high index of suspicion by primary care providers is needed to consider the diagnosis. There is not a single "gold standard" diagnostic test for PCD and multiple diagnostic methods coupled with specialized expertise is often needed to make the diagnosis. Patients with PCD also have comorbidities requiring a multidisciplinary approach for optimal clinical management. It is important for primary care physicians to recognize the PCD clinical phenotype and have a diagnostic framework for these patients. [Pediatr Ann. 2022;51(2):e82-e85.].

Variations in infection control practices suggest a need for guidelines in primary ciliary dyskinesia patient care.

Primary ciliary dyskinesis (PCD) is an autosomal recessive disorder associated with impaired mucociliary clearance caused by defects in ciliary structure and function. The major clinical feature of PCD is recurring or persistent respiratory tract infection. Respiratory tract colonization with drug-resistant organisms impacts the frequency of infections and lung function decline. Protective gear has been employed by caregivers in an attempt to control respiratory tract bacterial spread between patients with cystic fibrosis, but use in PCD is not known. We conducted a web-based survey to investigate infection control and prevention practices of PCD centers in North America, and how practices have been influenced by the COVID-19 pandemic. The response rate was 87.0%. Before the COVID-19 pandemic, glove, gown, and mask use were variable, and only 3.7% of centers used masks during encounters with PCD outpatients. After COVID-19 mandates are lifted, 48.1% of centers plan to continue to use masks during outpatient care, while the practice regarding the use of gloves and gowns was not influenced by the current pandemic. There is no uniform practice for infection control in PCD care indicating the need for practice guidelines. Mitigation of respiratory virus transmission learned during the COVID-19 pandemic may impact future infection control approaches used for patients with PCD and other lung diseases.

[Primary ciliary dyskinesia in children. Role of electron microscopy in countries with medium economic resources]. / Discinesia ciliar primaria en niños. Rol de la microscopia electrónica en países de medianos recursos económicos.

Primary ciliary dyskinesia (PCD) is a rare genetic disease that produces functional and structural de fects in the cilia. In Peru, no cases of this disease have been reported in the pediatric population. OBJECTIVE: To describe the clinical, radiological and ciliary ultrastructure characteristics in children with PCD, in a country with medium economic resources. CLINICAL CASE: We report 5 patients with PCD treated at the Instituto Nacional de Salud del Niño-Breña (Peru). Age range 1 to 5 years (median 3 years). Three patients were male. The most frequent clinical manifestations were chronic wet cough, rhonchi, coarse crackles, recurrent bronchial obstructive syndrome, and recurrent pneumonia. All patients had atelectasis, three had bronchiectasis, and two had dextrocardia with situs inversus. Two patients had undergone lobectomy. Other causes of recurrent pneumonias were ruled out with im munodeficiency study, chlorine test and pulmonary aspiration The electron microscopy showed ab sence of the inner arm of dynein as the most frequent pattern. All patients received treatment with antibiotics, nebulization with hypertonic saline, and respiratory physiotherapy with good adherence. CONCLUSION: In medium incomes countries, electron microscopy associated with clinical and radio logical characteristics plays an important role in the early diagnosis of this disease. This is the first Peruvian report that contributes to the casuistry and epidemiology of this rare pathology.

[Dyspnea and situs inversus in a boy aged 3 days].

A boy was admitted on day 3 after birth due to shortness of breath for 2 days and cyanosis for 1 day. He had clinical manifestations of dyspnea in the early postnatal period and situs inversus, and was finally diagnosed with Kartagener syndrome. His condition was improved after oxygen therapy, anti-infective therapy, and aerosol therapy. The genetic testing showed that there was a large-fragment loss of heterozygosity, exon 48_50, and a hemizygous mutation, c.7915C > T(p.R2639X), in the DNAH5 gene. Kartagener syndrome is a rare autosomal recessive disease, and this is the first case of Kartagener syndrome diagnosed in the neonatal period in China.

Nasopharyngeal carcinoma in a child with Kartagener`s syndrome.

BACKGROUND: Kartagener`s syndrome, a subgroup of primary ciliary dyskinesia, is characterized by situs inversus totalis, chronic sinusitis and bronchiectasis. To date, the association of malignant diseases and Kartagener`s syndrome has been reported and all cases except angioimmunoblastic T cell lymphoma in a child have been seen in adulthood. CASE: A 10-year-old boy who was followed with the diagnosis of Katagener`s syndrome, presented with a progressive mass in the cervical region for 6 months. Physical examination revealed mental retardation, multiple lymphadenopathies, the largest in the left cervical region (4x4 cm), and pectus carinatum. Also, on cardiovascular examination, apex beat was felt on the right fifth intercostal space along midclavicular line. Magnetic resonance imaging of nasopharynx showed narrowing of the nasopharyngeal airway with an increase in wall thickness up to 2.5 cm on the posterior wall of the nasopharynx. Also, bilateral multiple cervical lymphadenopathies were noted. The pathological examination of the biopsy from cervical lymphadenopathy revealed a diagnosis of undifferentiated nasopharyngeal carcinoma. Chemotherapy was started for nasopharyngeal carcinoma chemotherapy regimen including cisplatin, docetaxel, and 5-fluorouracil. After four cycles of chemotherapy there was a significant regression in nasopharyngeal mass and lymphadenopathies. The patient underwent radiotherapy to the nasopharynx and bilaterally cervical regions. The patient has been in follow-up for 6 years well and tumor free. However, he is still under the supervision of the pediatric immunology and allergy departments due to recurrent respiratory infections and sinusitis. CONCLUSION: We present a case of nasopharyngeal carcinoma which developed in a child with Kartagener`s syndrome. To our knowledge, this is the first report of nasopharyngeal carcinoma in a child with Kartagener`s Syndrome.

[Management of Primary Ciliary Dyskinesia]. / Management der Primären Ciliären Dyskinesie.

Primary Ciliary Dyskinesia (PCD, MIM 242650) is a rare, hereditary multiorgan disease characterized by malfunction of motile cilia. Hallmark symptom is a chronic airway infection due to mucostasis leading to irreversible lung damage that may progress to respiratory failure. There is no cure for this genetic disease and evidence-based treatment is limited. Until recently, there were no randomized controlled trials performed in PCD, but this year, data of the first placebo-controlled trial on pharmacotherapy in PCD were published. This cornerstone in the management of PCD was decisive for reviewing currently used treatment strategies. This article is a consensus of patient representatives and clinicians, which are highly experienced in care of PCD-patients and provides an overview of the management of PCD. Treatments are mainly based on expert opinions, personal experiences, or are deduced from other lung diseases, notably cystic fibrosis (CF), COPD or bronchiectasis. Most strategies focus on routine airway clearance and treatment of recurrent respiratory tract infections. Non-respiratory symptoms are treated organ specific. To generate further evidence-based knowledge, other projects are under way, e. g. the International PCD-Registry. Participating in patient registries facilitates access to clinical and research studies and strengthens networks between centers. In addition, knowledge of genotype-specific course of the disease will offer the opportunity to further improve and individualize patient care.

[Primary Ciliary Dyskinesia - Interdisciplinary Diagnostics and Therapy]. / Primäre Ziliendyskinesie (PCD) ­ interdisziplinäre Diagnostik und Therapie.

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disease. First respiratory symptoms already occur within the first hours after birth. Major symptoms are an unexplained neonatal respiratory distress syndrome, situs inversus, persistant cough, and chronic nasal congestion, recurrent paranasal sinus disorders with or without polyps, bronchiectasis as well as male infertility. Diagnostics is complex and includes transmission electron microscopy, nasal NO assessment, high-speed video microscopy and genetic evaluations. This review gives an overview over the current diagnostic procedures and therapeutic options. The management of PCD is a multidisciplinary approach, which should be reserved to in highly specialized centers.

Diagnóstico de la discinecia ciliar primaria / Diagnosis of the primary ciliary dyskinesia

Primary ciliary dyskinesia is a congenital disorder due to abnormal motile ciliary function, especially in the airway epithelium. The mucociliary clearance is impaired, producing reoccurring respiratory tract infections, usually resulting in bronchiectasis as an adult. Patients also have frequent ear and sinus infections and almost 50% of them have situs inversus. Diagnosis of primary ciliary dyskinesia is difficult because there is not a single gold standard test, resulting in the need of a multi-test approach. Until recently in our country we only had transmission electron microscopy, but nasal nitric oxide and high speed video microscopy are now available. In this article we will detail the most important clinical characteristics that make us suspect the presence of primary ciliary dyskinesia at different ages and the methods available for its diagnosis.

La discinesia ciliar primaria es una enfermedad congénita debida a una alteración del movimiento normal de los cilios, especialmente a nivel del epitelio respiratorio. Esto se traduce en una alteración del clearance mucociliar lo que predispone al paciente a tener infecciones respiratorias repetidas, terminando en la aparición de bronquiectasias en la edad adulta. También son frecuentes las infecciones repetidas de oídos y cavidades perinasales. La presencia de situs inverso puede verse en hasta en 50% de los pacientes con esta enfermedad. El diagnóstico de discinesia ciliar primaria es difícil ya que no existe un examen que sea considerado patrón de oro, por lo que se requiere la realización de distintos exámenes. En nuestro país hasta hace poco tiempo solo contábamos con la microscopía electrónica, pero recientemente se ha sumado la medición de óxido nítrico nasal y la videomicroscopía de alta velocidad. En el presente artículo se detallarán las características clínicas más importantes que hacen sospechar la presencia de DCP en las distintas edades y los métodos disponibles para su diagnóstico.

Tratamiento de la discinecia ciliar primaria / Treatmen of ciliary primary discinesia

At present, there is no specific treatment for primary ciliary dyskinesia, nor controlled and randomized clinical trials to determine how the management and monitoring of these patients should be considered. The therapeutic options are extrapolated from other diseases, such as cystic fibrosis, or non-cystic fibrosis bronchiectasis. However, the implementation of specific groups of experts, both in the USA (PDC-foundation) and in Europe (BESTCILIA or BEAT-PD), are helping to increase knowledge of the disease, opening research channels and seeking new treatments. Until we have therapies capable of correcting the basic defect of the disease, the pillars of treatment are the daily cleansing of the airways and aggressive antibiotherapy against respiratory infections. Multidisciplinary care in specialized centers where pulmonary function is monitored and the infection is prevented and treated will improve, as in cystic fibrosis, the results of patients.

En la actualidad no existe un tratamiento específico para la discinesia ciliar primaria, ni se cuenta con ensayos clínicos controlados y randomizados que permitan determinar cómo debe plantearse el manejo y seguimiento de estos pacientes. Las opciones terapéuticas son extrapoladas de otras enfermedades, como la fibrosis quística, o las bronquiectasias no fibrosis quística. Sin embargo, la puesta en marcha de grupos específicos de expertos, tanto en USA (PDC-foundation) como en Europa (BESTCILIA o BEAT-PD), están permitiendo incrementar el conocimiento de la enfermedad, abriendo vías de investigación y buscando nuevos tratamientos. Hasta contar con terapias capaces de corregir el defecto básico de la enfermedad, los pilares del tratamiento son la limpieza diaria de las vías aéreas y la antibioterapia agresiva frente a las infecciones respiratorias. La atención multidisciplinar en centros especializados donde se monitorice la función pulmonar y se prevengan y traten las infecciones mejorará, como en la fibrosis quística, los resultados de los pacientes.

Primary ciliary dyskinesia among Arabs: Where do we go from here?

Primary ciliary dyskinesia (PCD), also known as immotile-cilia syndrome, is a rare genetic disease that is inherited in an autosomal recessive manner. Several studies have explored certain aspects of PCD in the Arab world, yet much is still lacking in terms of identifying the different characteristics of this disease. In this paper, we aim to briefly cover those studies published about PCD in Arab countries, as well as to provide recommendations and guidelines for future studies.

Kartagener's syndrome: a case report.

BACKGROUND: Kartagener's syndrome is a subset of primary ciliary dyskinesia, an autosomal recessive inherited disorder characterized by the clinical triad of chronic sinusitis, bronchiectasis, and situs inversus. Abnormal ciliary structure or function leading to impaired ciliary motility is the main pathophysiologic problem in Kartagener's syndrome. CASE PRESENTATION: A 24-year-old man from Gondar town, North-West Ethiopia, presented to University of Gondar Hospital with recurrent episodes of nasal congestion with itching and paranasal discomfort, and productive cough for more than a decade. Clinical and imaging findings revealed chronic sinusitis, bronchiectasis, dextrocardia, and situs inversus. He was treated with orally administered antibiotics, mucolytic, and chest physiotherapy. He was symptomatically better with the above therapy, and started on a long-term low-dose prophylactic antibiotic. CONCLUSIONS: Patients with Kartagener's syndrome exist in Ethiopia as cases of chronic recurrent sinopulmonary infections. As there is no easy, reliable non-invasive diagnostic test for Kartagener's syndrome and the correct diagnosis is often delayed by years, it may cause chronic respiratory problems with reduced quality of life. Genetic counseling and fertility issues should be addressed once Kartagener's syndrome is diagnosed.