China
Africa
Explore chapters and articles related to this topic
Pathophysiology of Sleep-Disordered Breathing in Children and Neonates
Published in Susmita Chowdhuri, M Safwan Badr, James A Rowley, Control of Breathing during Sleep, 2022
Sofia Konstantinopoulou, Ignacio E Tapia
This is a rare disorder of respiratory and autonomic regulation, usually presenting in newborns and occasionally in older children and adults due to PHOX2B gene mutation (67). The neonatal presentation is typically associated with larger polyalanine repeat mutation of the PHOX2B gene. Patients with CCHS have intact voluntary control of ventilation but lack automatic control; and hypoventilation occurs either only during sleep or while awake and asleep. Patients usually have a decreased tidal volume and respiratory rate during sleep, thus requiring ventilatory support (68, 69). Although most patients breathe adequately during wakefulness, a subset requires ventilatory support 24 hr/day. However, even those who breathe adequately awake have been shown to have mild hypoventilation in association with increased metabolic demands such as exercise (70). CCHS may be associated with Hirschsprung's disease, autonomic dysfunction (decreased heart rate, hypotension) (71), neural tumors (ganglioneuromas, ganglioneuroblastomas), swallowing dysfunction when young (72), and minor ocular abnormalities (73).
Congenital Central Hypoventilation Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Expressed during neural development in the nuclei of brainstem areas that contain pathways controlling breathing and auditory functions [5], PHOX2B is regulated transcriptionally by itself, as well as E2a and Hand2 at specific sympathetic and enteric nervous system developmental stages. Other proteins that may play a possible role in the regulation of PHOX2B are SOX10, PHOX2A, and HASH1. Further, by forming trimer with Pbx1 and Meis1, Hoxb1 and Hoxb2 also contribute to the regulation of PHOX2B transcription.
Nonobstructive Sleep Patterns in Children
Published in Mark A. Richardson, Norman R. Friedman, Clinician’s Guide to Pediatric Sleep Disorders, 2016
Researchers examining the genetics of CCHS have concentrated on genes involved in the development and regulation of the ANS. The homeobox domain transcription factor PHOX2b appears to play a key role in the formation of the ANS pathways, and mutations in this gene have been found in the majority of CCHS patients. In a CCHS cohort from the United States, 65 of 67 patients (97%) had a polyalanine expansion of exon 3 within PHOX2b (18). The frequency of this mutation was lower in studies conducted outside the United States, but still accounted for a significant portion of the patients. PHOX2b mutation analysis should be considered in the diagnosis of CCHS. Chapter 16 discusses CCHS in greater detail.
The expression of PHOX2B in bone marrow and peripheral blood predicts adverse clinical outcome in non-high-risk neuroblastoma
Published in Pediatric Hematology and Oncology, 2022
Hongjun Fan, Tianyu Xing, Huimin Hong, Chao Duan, Wen Zhao, Qian Zhao, Xisi Wang, Cheng Huang, Shuai Zhu, Mei Jin, Yan Su, Chao Gao, Xiaoli Ma
The 2-year EFS and OS rates of the 132 patients were 94.7 ± 2.0%, and 97.7 ± 1.3%, respectively, with a median follow-up time of 28.5 months (range, 3–44 months). As shown in Figure 2 and 3, patients with a positive PHOX2B expression in BM and PB samples at diagnosis had lower EFS and OS rates than those with no PHOX2B expression (p < 0.001). The 2-year EFS rates were 76.9 ± 8.3% and 63.6 ± 14.5% in patients with a positive PHOX2B expression in BM and PB samples, respectively, at diagnosis. The patients with INRGSS stages M and MS, 1p LOH, and high levels of LDH, SF and NSE had significantly decreased 2-year EFS rates (p < 0.05). The expression of PHOX2B in BM and PB samples at diagnosis also affected the 2-year OS (88.5 ± 6.3% and 81.8 ± 11.6%). The 2-year OS rates were poorer in patients with high levels of LDH and SF, and 11q LOH (p < 0.05) (Table 3). Multivariate analysis showed that the positive PHOX2B expression in BM [hazard ratio (HR): 22.28, 95% confidence interval: 2.45–202.49, P = 0.006], and PB (HR: 4.41, 95% confidence interval: 1.08–18.02, P = 0.039) samples at diagnosis were both significant predictors of a low EFS. The number of event occurrences in patients with different clinical characteristics is also shown in Table 3. The details of all the 9 patients experiencing relapse or progression during the follow-up are shown in Table 4. There were 18 patients for whom the expression of PHOX2B was detected in the BM while demonstrating no evidence of involvement with neuroblastoma by BM cytology/immunocytology. The clinical characteristics of these patients are shown in Table 5. The 2-year EFS and OS of the 18 patients were both 94.4 ± 5.4%.
Advances in the molecular biology and pathogenesis of congenital central hypoventilation syndrome—implications for new therapeutic targets
Published in Expert Opinion on Orphan Drugs, 2018
Simona Di Lascio, Roberta Benfante, Silvia Cardani, Diego Fornasari
The discovery that PHOX2B is the CCHS-causing gene has shed light on the role of this transcription factor in the development of a subset of neurons that are crucial for respiratory functions. Over the last 20 years, intensive research has revealed its normal function and the molecular effects of its mutations and aberrant function. The generation of animal and cellular models has helped to clarify various aspects of the molecular mechanisms of PHOX2B mutations and the pathogenesis of CCHS, and histopathological findings have recently provided new insights into the pathological processes of the disease.
Congenital central hypoventilation syndrome: diagnosis and management
Published in Expert Review of Respiratory Medicine, 2018
Melissa A. Maloney, Sheila S. Kun, Thomas G. Keens, Iris A. Perez
Confirmation of the PHOX2B gene mutation is highly important not only in establishing the diagnosis but also in providing anticipatory care. Although it is generally considered that patients with 20/27 and longer PARMs and NPARMs will have a more severe phenotype, recent reports point to a variable phenotypic presentation. For example, patients with these genotypes generally require full-time ventilatory support, but we have reported cases who are ventilator dependent only during sleep. Thus, approach to each patient must be individualized.