scholarly journals Research Advances on Therapeutic Approaches to Congenital Central Hypoventilation Syndrome (CCHS)

2021 ◽  
Vol 14 ◽  
Author(s):  
Simona Di Lascio ◽  
Roberta Benfante ◽  
Silvia Cardani ◽  
Diego Fornasari
Keyword(s):  
Protein Misfolding ◽  
Current Knowledge ◽  
Genetic Disorder ◽  
Congenital Central Hypoventilation Syndrome ◽  
Therapeutic Approaches ◽  
Transcriptional Dysregulation ◽  
Central Hypoventilation ◽  
Hypoventilation Syndrome

Congenital central hypoventilation syndrome (CCHS) is a genetic disorder of neurodevelopment, with an autosomal dominant transmission, caused by heterozygous mutations in the PHOX2B gene. CCHS is a rare disorder characterized by hypoventilation due to the failure of autonomic control of breathing. Until now no curative treatment has been found. PHOX2B is a transcription factor that plays a crucial role in the development (and maintenance) of the autonomic nervous system, and in particular the neuronal structures involved in respiratory reflexes. The underlying pathogenetic mechanism is still unclear, although studies in vivo and in CCHS patients indicate that some neuronal structures may be damaged. Moreover, in vitro experimental data suggest that transcriptional dysregulation and protein misfolding may be key pathogenic mechanisms. This review summarizes latest researches that improved the comprehension of the molecular pathogenetic mechanisms responsible for CCHS and discusses the search for therapeutic intervention in light of the current knowledge about PHOX2B function.

scholarly journals Presentation and Treatment of Monozygotic Twins with Congenital Central Hypoventilation Syndrome

2011 ◽  
Vol 18 (2) ◽  
pp. 87-89 ◽  
Author(s):  
Reshma Amin ◽  
Andrea Riekstins ◽  
Suhail Al-Saleh ◽  
Colin Massicotte ◽  
Allan L Coates ◽  
...  
Keyword(s):  
Genetic Disorder ◽  
Noninvasive Positive Pressure Ventilation ◽  
Monozygotic Twins ◽  
Monozygotic Twin ◽  
Clinical Severity ◽  
Positive Pressure ◽  
Congenital Central Hypoventilation Syndrome ◽  
Current Case ◽  
Central Hypoventilation ◽  
Hypoventilation Syndrome

Congenital central hypoventilation syndrome is a rare genetic disorder characterized by hypoventilation during sleep secondary to a blunted response to hypercapnia and hypoxia. The current case report describes developmentally normal four-year-old monozygotic twin boys who presented in infancy with variable presentations and clinical severity of congenital central hypoventilation syndrome. Both were managed with noninvasive positive pressure ventilation.

Congenital Central Hypoventilation Syndrome in Neonates: Report of Fourteen New Cases and A Review of the Literature

2020 ◽  
Author(s):  
Mei Mei ◽  
Lin Yang ◽  
Yulan Lu ◽  
Laishuan Wang ◽  
Guoqiang Cheng ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Molecular Testing ◽  
Congenital Central Hypoventilation Syndrome ◽  
Phenotype Correlation ◽  
Mild Phenotype ◽  
Pathogenic Variants ◽  
Neonatal Onset ◽  
Genotype Phenotype Correlation ◽  
Central Hypoventilation ◽  
Hypoventilation Syndrome

Abstract Background: Congenital central hypoventilation syndrome (CCHS) is a rare autosomal dominant disorder caused by pathogenic variants in PHOX2B gene. Characteristics of neonatal-onset CCHS cases have not been well assessed. Our study aimed to expand current knowledge of clinical and genetic features of neonates with CCHS and provide data on the genotype-phenotype correlation.Methods: We made a retrospective analysis of 14 neonates carrying PHOX2B pathogenic variants from 2014 to 2019 and we reviewed previously published neonatal-onset cases. Clinical and genetic data were analyzed. Moreover, genotype-phenotype correlation analysis was performed.Results: We identified a total of 60 cases with neonatal-onset CCHS including 14 novel cases from our local cohort. Nearly 20% (18.2%, 10/55) of the patients were born prematurely. Nearly half (46.2%, 18/39) of the patients had abnormal family history. Polyhydramnios was observed in 21.3% (10/47) of the patients. About 90% of the patients manifested hypoventilation in the first week. Forty-six (76.7%) patients were classified as severer-CCHS. Gastrointestinal manifestations were observed in 71.7% of the patients. Approximately twofold more males than females were affected by Hirschprung disease (HSCR)/variant HSCR (75.8% vs 35%, P=0.003). Neural crest tumor occurred in 9.1% (4/44) patients. Half patients had PARMs in PHOX2B and the left had 23 distinct non-PARMs (NPARMs) with one novel variant (c.684dup). The prevalence of HSCR and mild-CCHS among patients with NPARMs was significantly greater than that of the patients with PARMs.Conclusions: This report provides a large cohort of neonatal-onset CCHS cases. The results indicate that severe hypoventilation and HSCR are frequently observed in this group. NPARMs accounted for half of the cohort with some genotypes tend to be associated with mild phenotype. Molecular testing in suspicious neonates and genetic counseling for CCHS families are highly recommended.

scholarly journals Genetic study of apatient with congenital central hypoventilation syndrome in Iran: a case report

2021 ◽  
Author(s):  
Reihaneh Khorasanian ◽  
Marzieh Mojbafan ◽  
Nastaran Khosravi
Keyword(s):  
Genetic Analysis ◽  
Genetic Study ◽  
Genetic Disorder ◽  
Repeat Expansion ◽  
Congenital Central Hypoventilation Syndrome ◽  
The Family ◽  
Central Hypoventilation ◽  
Genetics And Genomics ◽  
Hypoventilation Syndrome ◽  
Expansion Mutation

Abstract I. Background: Congenital central hypoventilation syndrome (CCHS) is an extremely rare genetic disorder characterized by autonomic nervous system (ANS) dysregulation caused by mutations in the PHOX2B gene. Here we introduce the first genetic analysis of a CCHS patient in Iran.II. Methods and Results: Genetic analysis of the PHOX2B gene was performed by Sanger sequencing and interpreted using the American College of Medical Genetics and Genomics (ACMG) guideline. The results showed a heterozygous duplication in the exon 3 causing a polyalanine repeat expansion mutation (PARMs) to 27 repeats in the PHOX2B gene (20/27 genotype). The patient’s parents were normal for this mutation.III. Conclusions: According to the ACMG guideline, the mutation is a pathogenic one, and it was a denovo mutation in the family. The genetic study can help the family for prenatal diagnosis or pre-implantation diagnosis if the parents have gonadal mosaicism.

scholarly journals Adolescent Congenital Central Hypoventilation Syndrome: An Easily Overlooked Diagnosis

2021 ◽  
Vol 18 (24) ◽  
pp. 13402
Author(s):  
Marta Ditmer ◽  
Szymon Turkiewicz ◽  
Agata Gabryelska ◽  
Marcin Sochal ◽  
Piotr Białasiewicz
Keyword(s):  
Genetic Disease ◽  
Pediatric Patients ◽  
Late Onset ◽  
Current Knowledge ◽  
Adolescent Female ◽  
Congenital Central Hypoventilation Syndrome ◽  
Respiratory Drive ◽  
Central Hypoventilation ◽  
Hypoventilation Syndrome ◽  
Made In

Congenital central hypoventilation syndrome (CCHS), also known as Ondine’s curse, is a rare, potentially fatal genetic disease, manifesting as a lack of respiratory drive. Most diagnoses are made in pediatric patients, however late-onset cases have been rarely reported. Due to the milder symptoms at presentation that might easily go overlooked, these late-onset cases can result in serious health consequences later in life. Here, we present a case report of late-onset CCHS in an adolescent female patient. In this review we summarize the current knowledge about symptoms, as well as clinical management of CCHS, and describe in detail the molecular mechanism responsible for this disorder.

CONGENITAL CENTRAL HYPOVENTILATION SYNDROME ASSOCIATED WITH HIRSCHSPRUNG’S DISEASE

2018 ◽  
Vol 5 (3) ◽  
pp. 32-36
Author(s):  
Daniel Jhonatas Silvério De Lima ◽  
Nadine Nair De Pina Tavares ◽  
Lucas dos Santos Alcantara ◽  
Lúcia Caetano Pereira ◽  
Andrea Silva Do Amaral
Keyword(s):  
Sleep Apnea ◽  
Hirschsprung's Disease ◽  
Hirschsprung’S Disease ◽  
Life Support ◽  
Genetic Disorder ◽  
Central Sleep Apnea ◽  
Clinical Aspects ◽  
Congenital Central Hypoventilation Syndrome ◽  
Central Hypoventilation ◽  
Hypoventilation Syndrome

RESUMO A síndrome de hipoventilação central congênita (SHCC) é uma desordem genética rara, associada a mutações no gene paired-like homeobox 2B (PHOX2B), caracterizada por disautonomia e apneia central. A doença de Hirschsprung (DH) está presente em cerca de 20% dos casos de SHCC. Este estudo objetiva relatar o caso de um neonato que apresentou apneia central recorrente, eliminação tardia de mecônio e distensão abdominal diagnosticado com DH associada a SHCC, comparando-se os aspectos clínicos esperados e os encontrados pela equipe que assistiu a criança. Nota-se um retardo no diagnóstico principalmente pela raridade da síndrome e ao seu desconhecimento por parte dos profissionais da saúde. Sendo assim, conclui-se ser imprescindível medidas de suporte, diagnóstico e tratamento precoces pelo risco de complicações graves que ambas as doenças podem acarretar ao recém nascido.   Palavras-chave: Síndrome de hipoventilação central congênita, síndrome de Ondine, gene PHOX2B, doença de Hirschsprung,  síndrome de Haddad. ABSTRACT Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder associated with mutations in paired-like homeobox 2B gene (PHOX2B), characterized by dysautonomia and central sleep apnea. Hirschsprung's disease (HD) is present in about 20% of CCHS cases. This study aims to report the case of a neonate who presented with sleep apnea, late elimination of meconium and abdominal distension diagnosed with CCHS associated with HD, comparing the clinical aspects expected and those found by the medical team that attended the child. There was a delay in the diagnosis, mainly due to the rarity of the syndrome and the lack of knowledge about the disease by health professionals. Therefore, it is concluded that life support, early diagnosis, and treatment are essential due to the risk of serious complications that both diseases can cause to the newborn. Keywords: Congenital central hypoventilation syndrome, Ondine’s curse, PHOX2B gene, Hirschsprung's disease, Haddad syndrome.

Modulation of Matrix Metalloproteinases by Plant-Derived Products

2020 ◽  
Vol 20 ◽  
Author(s):  
Nur Najmi Mohamad Anuar ◽  
Nurul Iman Natasya Zulkafali ◽  
Azizah Ugusman
Keyword(s):  
Clinical Trials ◽  
Natural Products ◽  
Matrix Metalloproteinases ◽  
Animal Studies ◽  
Current Knowledge ◽  
In Vitro Models ◽  
In Vivo Studies ◽  
Extracellular Matrix Components

: Matrix metalloproteinases (MMPs) are a group of zinc-dependent metallo-endopeptidase that are responsible towards the degradation, repair and remodelling of extracellular matrix components. MMPs play an important role in maintaining a normal physiological function and preventing diseases such as cancer and cardiovascular diseases. Natural products derived from plants have been used as traditional medicine for centuries. Its active compounds, such as catechin, resveratrol and quercetin, are suggested to play an important role as MMPs inhibitors, thereby opening new insights into their applications in many fields, such as pharmaceutical, cosmetic and food industries. This review summarises the current knowledge on plant-derived natural products with MMP-modulating activities. Most of the reviewed plant-derived products exhibit an inhibitory activity on MMPs. Amongst MMPs, MMP-2 and MMP-9 are the most studied. The expression of MMPs is inhibited through respective signalling pathways, such as MAPK, NF-κB and PI3 kinase pathways, which contribute to the reduction in cancer cell behaviours, such as proliferation and migration. Most studies have employed in vitro models, but a limited number of animal studies and clinical trials have been conducted. Even though plant-derived products show promising results in modulating MMPs, more in vivo studies and clinical trials are needed to support their therapeutic applications in the future.

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