LESS SENSITIVE TO PAIN,LESS ANXIETY-MAY BE CCHS(ONDINE CURSE)-DR.D.K.JHA,M.D
Congenital hypoventilation syndrome(CCHS) is a rare disorder.
It has myriad clinical presentations,affecting various systems.
It may present at birth or in adulthood depending on mutations.
If it presents in neonatal period,the person becomes ventilator dependent but lator on,may require ventilator only during sleep.
If it presents in adulthood,the person remains asymtomatic during entire childhood period.
Some affected individual becomes symptomatic only during respiratory infections,sedations or during anesthesia due to other surgical reasons.
Some individuals get detected only when there is great difficulties in weaning from ventilator due to any cause.
Some children get detected when they have abnormally high capacity to hold breath for a prolonged period.
Some adults and adolescents have been diagnosed only after they showed abnormally high capacity for a prolonged period to swim underwater.
Some affected individuals may have excessive episodic perspirations(sweating).
Affected individuals may be less sensitive to pain or less anxious in situations where normal individuals have symptoms of anxiety.
There is no sign of respiratory distress even when they are severly hypoxic or hypercapneic.
Following are the clinical manifestations from different systems/Organs:
RESPIRATORY SYSTEM; Alveolar hypoventilation,decreased perception of dyspnea
CARDIOVASCULAR SYSTEM:Increased sinus pause(more than 3 seconds),low day time blood pressure
orthostatic hypotension,bradycardia,less increase in BP after exercise,syncope
NERVOUS SYSTEM:less perception of pain,less anxiety,neurocognitive defect,sizure
GASTROINTESTINAL:Oesophageal dismotility,constipation,in 20%cases may Hirschprungs disease
ENDOCRINE:Hyperglycemia,hypoglycemia,hyperinsulinism
SKIN:Sporadic excessive swaeting
TUMOURS:Neuroblastoma,ganglioneuroma
OTHERS:Low baseline body temperature,heat tolerance may be poor.
CLINICAL PRESENTATIONS:In most of the cases it presents in neonatal period with apnea,hypoventilation of central origin with hypoxemia,hypercapnea and cyanosis.They require assisted ventilation,invasive or non invasive to survive.Once put on ventilator,they are unable to be weaned off from ventilator.As they grow and mature,some require assisted ventilation only during sleep.
Children and adults present with unexplained apnea,respiratory failure during respiratory infections or sedation requiring assisted ventilation.There is no sign of respiratory distress even they are severly hypoxemic or hypercapneic.They may present with unexplained seizure due to undetected hypoxemiaand/or hypercapnea for a prolonged period.
They may show unusual capacity to hold breath for a long time and unusually high capacity for underwater swimming. They may present with features of right heart failure confusing with congenital heart disease.
Older children and adults may present with features of pulmonary hypertension,or cor pulmonale
CAUSES: Respiration is initiated by peripheral chemreceptors located in aortic and carotid bodies, which mainly sense changes in Po2 and to a lesser extent Pco2 and PH ,and central chemreceptors located in medulla, which sense changes in Pc02 and PH.Respiration is controlled by the centre located in medulla and pons which integrate the inputs from chemoreceptors and send signal to the respiratory muscles to perform the process of breathing.
PHOX2B gene, located on chromosome 4p12, is a protein comprising 314 amino acids with two short and stable polyalanine repeats of 9 and 20 residues in the C terminus. It encodes for highly conserved homeodomain transcription factor that is essential in the development of Respiratory control NEURONS and ANS.
CCHS is a result of mutational defect in PHOX2B gene.Normal PHOX2B gene has 20 alanine repeats (20/20 genotype). The majority of CCHS patients have polyalanine repeat mutations(PARM).
Variable clinical manifestations are the results of variable mutations.
DIAGNOSIS: After ruling out other cause of hypoventilations,by approriate investigations,all suspected cases should be confirmed by gene mutatin analysis for PHOX2B gene.There 3 methods available currently.
1.PHOX2B targeted mutation analysis
2.PHOX2B sequence analysis
3. Deletion/duplication test
MANAGEMENT: Goal of management is to provide adequate ventilatory support during both sleep and awake states to maintain pco2 at near to 35mmhg and aeterial saturation above 95%.For asymptomatic patients,it is important to remember that they may go intrespiratory decompensation while in stress,infections or sedations.
As these patients are unable to sense hypoxia as well as hypercarbia,spo2 monitoring and tco2 monitoring particularly during sleep is important.
MODES OF VENTILATORY SUPPORT:Invasive positive pressure ventilation through tracheostomy
Non invasive positive pressure ventilation
Diaphragmatic pacing
GENETIC COUNCELLING:PHOX2B gene mutation has autosomal pattern of inheritance with variable penetrance.
Genetic counseling is important as there is 50% chance of recurrence with each
child.So if a parent is affected,there is 50% chance for siblings to get
affected
It is important to test parents of affected child even if they are asymptomatic.
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Tags: central hypoventilation, n, Ondine curse