Congenital central hypoventilation syndrome (Ondine's curse syndrome) in two siblings: Delayed diagnosis and successful noninvasive treatment

Congenital central hypoventilation syndrome (CCHS, Ondine's curse syndrome) is a rare respiratory disorder; less than 100 cases have been reported. Familiality of the disease has been discussed, but only few familial cases have been reported so far. In this report we describe the occurrence of CCHS in two male siblings. Diagnosis was established only at the age of 4 years in the first case, although the patient had disease related symptoms since early infancy. The second patient was one of dizygotic twins, he was diagnosed with CCHS at the age of 8 months. Up to that age only moderate desaturations had been observed. The other twin was unaffected by the disease. Both patients were successfully treated by nocturnal positive-pressure ventilation via a specially adapted face mask. They show satisfactory physical and neurologic development.     

Early use of Nasal-BiPAP in two infants with Congenital Central Hypoventilation syndrome

Aim: To reduce the problems caused by prolonged artificial ventilation in babies with Congenital Central Hypoventilation syndrome (CCHS). Methods: Two term infants with CCHS, weighing 4030 g and 3100 g, respectively, at the beginning of treatment and aged 53 and 31 d, respectively, were successfully ventilated with a Nasal Bilevel Positive Airway Pressure (N-BiPAP) device. Results: In the first patient the tcPO ₂ recordings (mean ± SD) during sleep were 46 ± 12 mmHg before using N-BiPAP and 58 ± 13 mmHg after using the device, while those for tcPCO ₂ were 75 ± 9 mmHg and 49 ± 11 mmHg, respectively. In the second patient tcPO ₂ during sleep was 42 ± 3 mmHg before, and 55 ± 5 after N-BiPAP, and for tcPCO ₂ the recordings were 119 ± 24 mmHg and 55 ± 6 mmHg, respectively, showing a significant improvement. One infant had persistent gastro-oesophageal reflux, and frontal skin abrasion caused by the face mask. Nevertheless, these complications did not necessitate the discontinuation of N-BiPAP ventilation, thus precluding prolonged use of intubation and tracheotomy.

Conclusion: In infants with CCHS, early use of non-invasive, positive-pressure ventilation with N-BiPAP, in association with careful monitoring, can decrease problems caused by prolonged intubation and tracheotomy.     

TOTAL AGANGLIONOSIS OF THE COLON (HIRSCHSPRUNG'S DISEASE) and CONGENITAL FAILURE OF AUTOMATIC CONTROL OF VENTILATION (ONDINE'S CURSE)

Abstract. Stern, M., Hellwege, H. H., Grävinghoff, L. and Lambrecht, W. (Department of Paediatrics and Department of Surgery, University Hospital Eppendorf, Hamburg, Federal Republic of Germany). Total aganglionosis of the colon (Hirschsprung's disease) and congenital failure of automatic control of ventilation (Ondine's curse). Acta Paediatr Scand, 70:121, 1981.–Total aganglionosis of the colon presenting with small intestinal obstruction in the neonatal period was observed in combination with congenital alveolar hypoventilation requiring continuous mechanical ventilation in a boy. The patient died aged 15 months from acute dehydration due to enteritis, long after total resection of the aganglionic bowel had been performed. Pulmonary hypertension was found in the newborn period. There was progressive right ventricular myocardial hypertrophy. This is the fourth case reported with a combination of defects involving nerve cell function of the brain stem and gastrointestinal tract.     

Heart block following propofol in a child

We present the case of a nine-year-old boy afflicted with Ondine's curse, who developed complete atrioventricular heart block after a single bolus of propofol for induction of anaesthesia for strabismus surgery. Ondine's curse, the other name for congenital central hypoventilation syndrome, is characterized by a generalized disorder of autonomic function. Propofol has no effect on the normal atrioventricular conduction system in humans but it reduces sympathetic activity and can highly potentiate other vagal stimulation factors. Heart block has been documented after propofol bolus use in adults but, to our knowledge, not in children. It would appear that propofol is not a good choice for anaesthesia in congenital central hypoventilation syndrome.     

Developments in autonomic research: a review of the latest literature

Congenital central hypoventilation syndrome (CCHS) is a developmental disorder of childhood, characterized by respiratory arrests during sleep. Initially referred to as Ondine’s Curse, children with CCHS show attenuated ventilatory responses to hypercapnia and hypoxia, develop life-threatening episodes of apnea with cyanosis, and require ventilatory support during sleep. In addition, there is evidence of other developmental disorders in these children. It is now widely accepted that the syndrome is due to a mutation in a single homeobox gene located on chromosome 4. PHOX2B is important for the normal development of the autonomic nervous system and is expressed in respiratory neurones in the parafacial region of the ventral medualla: mice with mutations in PHOX2B breathe irregularly, do not respond to hypercapnia and die shortly after birth from central apnea. Cardiovascular disturbances, including prolonged R-R intervals and sudden death, are directly related to the extent of the mutation in PHOX2B.     

Diaphragmatic pacing for the treatment of congenital central alveolar hypoventilation syndrome

Purpose

The congenital central alveolar hypoventilation syndrome (CCAHS), also known as Ondine curse, is characterized by the absence of adequate autonomic control of respiration.The purpose of our study is to review our 20-year experience with diaphragmatic pacing as a treatment modality for CCAHS.

Methods

After obtaining institutional review board approval, the medical records of all 6 patients who currently are in the diaphragmatic pacing program at the Montreal Children's Hospital, Montreal, QC, Canada were reviewed. In addition to demographic details, associated anomalies were noted. Data regarding age at surgery, technical approach, and short- and long-term complications, including equipment failure and replacement, were noted. We were interested in the long-term outcome for this group of patients, particularly their quality of life.

Results

Our group of patients is composed of 4 females and 2 males. Their age ranges between 4 and 23 years. They were operated on at an average age of 47.8 months. The surgical approach used was mainly bilateral axillary thoracotomy. Internal component failure is the most common complication. All patients are ventilator free during the day. They all are active and productive, either attending school or working full time.

Conclusion

Diaphragmatic pacing is an effective treatment of Ondine disease. As equipment improved, there is much less need for replacement of components. Patients can lead a much more normal existence by being ventilator free at least during the day, enabling them to participate in normal daily activities.     

Congenital central hypoventilation syndrome associated with Hirschsprung's disease and neuroblastoma: Case of multiple neurocristopathies

We report on a male infant with the rare combined occurrence of congenital central hypoventilation syndrome (CCHS or Ondine's curse), Hirschsprung's disease (HD), and neuroblastoma. Current therapeutical options leave no doubt that children with isolated forms of CCHS, HD, or neuroblastoma must be treated, but management decisions and the ethical dilemma become more difficult with the presence of multiple neurocristopathies. Our patient was dependent on mechanical ventilation and total parenteral nutrition, when a neuroblastoma was diagnosed at age 5 months. We initiated an attempt at curative chemotherapy. The tumor failed to respond to recommended chemotherapeutic regimens, and the patient died at 11 months of age. We emphasize the importance of screening CCHS patients for associated illnesses such as neuroblastoma and ganglioneuroblastoma at time of diagnosis. Pediatr Pulmonol. 2002; 33:71–76. © 2002 Wiley‐Liss, Inc.     

延髓梗死继发Ondine's curse综合征2例报道及文献复习

延髓血供丰富,侧支循环较多,临床上延髓梗死患者少见,仅占脑干梗死的7%左右.但延髓梗死临床表现复杂多变,尤其是弥散加权成像(diffusion weighted imaging,DWI)阴性者,临床很难鉴别.此外,延髓梗死后继发Ondine's curse综合征,死亡率高,预后差.因此,对延髓梗死后易继发中枢性睡眠呼吸暂停的患者早期识别、诊断及防治尤为重要.现报告两例延髓梗死后继发Ondine's curse综合征如下,以期能为该病的临床诊断及治疗提供帮助.     

延脑梗死继发Ondine''''s curse综合征

目的　总结延脑梗死继发Ondine scurse综合征的临床特点及救治经验。方法　收集近年来观察的资料较完整经MR证实延脑梗死并继发中枢性呼吸衰竭共 5例 ,进行整理分析。结果　患者 5 6～ 73岁 ,均有多年高血压病及睡眠打鼾史 ;突发眩晕 ,以一侧Horner综合征及对侧痛觉减退为主的神经体征 ,安静的渐进性加重的中枢性呼吸衰竭及意识障碍 ;动脉血气分析呈明显的PaCO2 升高及PaO2 降低 ,MR示延脑梗死 ;经机械通气一定时间后恢复自主呼吸 ,快速停机再次陷入呼吸衰竭及昏迷 ,4例用逐渐延长停机间歇时间 ,最终达到脱机正常呼吸。结论　延脑梗死继发Ondine scurse综合征的主要临床特点是安静地渐进性加重的中枢性呼吸衰竭及意识障碍 ,基本救治措施是气管内机械通气 ,须逐渐延长间歇停机时间 ,才能达到脱机正常呼吸。