CHS is associated with respiratory arrests during sleep and, in some cases, to neuroblastoma (tumors of the sympathetic ganglia), Hirschsprung disease (partial agenesis of the enteric nervous system), dysphagia (difficulty swallowing) and anomalies of the pupilla. Other symptoms include darkening of skin color from inadequate amounts of oxygen, drowsiness, fatigue, headaches, and an inability to sleep at night. Those suffering from Ondine's curse also have a sensitivity to sedatives and narcotics, which makes respiration even more difficult. A low concentration of oxygen in the red blood cells also may cause hypoxia-induced pulmonary vasoconstriction and pulmonary hypertension, culminating in cor pulmonale or a failure of the right side of the heart. Associated complications may also include gastro-esophageal reflux, ophthalmologic issues, seizures, recurrent pneumonia, developmental delays, learning disabilities and episodes of fainting and temperature disregulation.

Children with CCHS develop life-threatening episodes of apnea with cyanosis, usually in the first months of life. Medical evaluation excludes lesions of the brain, heart, and lungs but demonstrates impaired responses to build-up of carbon dioxide (hypercapnia) and decreases of oxygen in the circulation (hypoxia), the two strongest stimuli to increase breathing rate.

Polysomnography shows that hypoventilation is most marked during slow-wave sleep. In the most severe cases, hypoventilation is present during other nonrapid eye movement sleep stages and even wakefulness. A subset of CCHS patients are at very high risk for developing malignant neural crest-derived tumors, such as neuroblastoma.

The sequence of "PHOX2B" reveals mutations in 91% of the cases.

As in many disorders that are very rare, an infant with this unusual form of sleep apnea suffers from the probability that their physician has most likely never seen another case and will not recognize the diagnosis. In some locations, such as France, optimal management of patients, once identified, has been aided by the creation of a national registry and the formation of a network of centers.

Obesity hypoventilation syndrome is a form of sleep disordered breathing. Two subtypes are recognized, depending on the nature of disordered breathing detected on further investigations. The first is OHS in the context of obstructive sleep apnea; this is confirmed by the occurrence of 5 or more episodes of apnea, hypopnea or respiratory-related arousals per hour (high apnea-hypopnea index) during sleep. The second is OHS primarily due to "sleep hypoventilation syndrome"; this requires a rise of CO levels by 10 mmHg (1.3 kPa) after sleep compared to awake measurements and overnight drops in oxygen levels without simultaneous apnea or hypopnea. Overall, 90% of all people with OHS fall into the first category, and 10% in the second.

Most people with obesity hypoventilation syndrome have concurrent obstructive sleep apnea, a condition characterized by snoring, brief episodes of apnea (cessation of breathing) during the night, interrupted sleep and excessive daytime sleepiness. In OHS, sleepiness may be worsened by elevated blood levels of carbon dioxide, which causes drowsiness ("CO narcosis"). Other symptoms present in both conditions are depression, and hypertension (high blood pressure) that is difficult to control with medication. The high carbon dioxide can also cause headaches, which tend to be worsening in the morning.

The low oxygen level leads to physiologic constriction of the pulmonary arteries to correct ventilation-perfusion mismatching, which puts excessive strain on the right side of the heart. When this leads to right sided heart failure, it is known as "cor pulmonale". Symptoms of this disorder occur because the heart has difficulty pumping blood from the body through the lungs. Fluid may, therefore, accumulate in the skin of the legs in the form of edema (swelling), and in the abdominal cavity in the form of ascites; decreased exercise tolerance and exertional chest pain may occur. On physical examination, characteristic findings are the presence of a raised jugular venous pressure, a palpable parasternal heave, a heart murmur due to blood leaking through the tricuspid valve, hepatomegaly (an enlarged liver), ascites and leg edema. Cor pulmonale occurs in about a third of all people with OHS.

The variable presentation of ROHHAD includes the following main symptoms:

- Hyperphagia and obesity by age of 10 years - (median age 3 years);

- Respiratory Manifestations:

- Alveolar Hypoventilation (median onset age 6.2 years);

- Cardiorespiratory arrest;

- Reduced Carbon Dioxide Ventilatory Response;

- Obstructive sleep apnea.

- Thermal or other hypothalamic dysregulations, with autonomic dysregulation by median age 3.6 years:

- Failed Growth Hormone Stimulation;

- Adipsic hypernatremia (inability to feel thirst to keep normal hydration);

- Hypernatremia;

- Hyperprolactinemia;

- Hyperphagia;

- Diabetes insipidus;

- Ophthalmologic Manifestations;

- Thermal Dysregulation;

- Gastrointestinal dysmotility;

- Altered Perception of Pain;

- Altered Sweating;

- Cold Hands and Feet.

- Neurobehavioral disorders;

- Tumors of neural crest origin.

Clinically overlapping cases exist because CCHS phenotype can also include autonomic nervous system dysregulation, or tumors of neural crest origin.

Acute respiratory acidosis occurs when an abrupt failure of ventilation occurs. This failure in ventilation may be caused by depression of the central respiratory center by cerebral disease or drugs, inability to ventilate adequately due to neuromuscular disease (e.g., myasthenia gravis, amyotrophic lateral sclerosis, Guillain–Barré syndrome, muscular dystrophy), or airway obstruction related to asthma or chronic obstructive pulmonary disease (COPD) exacerbation.

Respiratory acidosis can be acute or chronic.

- In "acute respiratory acidosis", the "Pa"CO is elevated above the upper limit of the reference range (over 6.3 kPa or 45 mm Hg) with an accompanying acidemia (pH <7.36).

- In "chronic respiratory acidosis", the "Pa"CO is elevated above the upper limit of the reference range, with a normal blood pH (7.35 to 7.45) or near-normal pH secondary to renal compensation and an elevated serum bicarbonate (HCO >30 mm Hg).

Disorders like congenital central hypoventilation syndrome (CCHS) and ROHHAD (rapid-onset obesity, hypothalamic dysfunction, hypoventilation, with autonomic dysregulation) are recognized as conditions that are associated with hypoventilation. CCHS may be a significant factor in some cases of sudden infant death syndrome (SIDS), often termed "cot death" or "crib death".

The opposite condition is hyperventilation (too much ventilation), resulting in low carbon dioxide levels (hypocapnia), rather than hypercapnia.

Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation and Autonomic Dysregulation (ROHHAD syndrome) is a very rare disease affecting approximately 75 people worldwide. Patients with ROHHAD, as well as patients with congenital central hypoventilation syndrome (CCHS) have damage to the mechanism governing proper breathing. ROHHAD syndrome is a disease that is potentially lethal and incurable. Fifteen patients with ROHHAD were evaluated by Diego Ize-Ludlow et al. work published in 2007.

Symptoms and signs of early hypercapnia include flushed skin, full pulse, tachypnea, dyspnea, extrasystoles, muscle twitches, hand flaps, reduced neural activity, and possibly a raised blood pressure. According to other sources, symptoms of mild hypercapnia might include headache, confusion and lethargy. Hypercapnia can induce increased cardiac output, an elevation in arterial blood pressure, and a propensity toward arrhythmias. Hypercapnia may increase pulmonary capillary resistance. In severe hypercapnia (generally PaCO greater than 10 kPa or 75 mmHg), symptomatology progresses to disorientation, panic, hyperventilation, convulsions, unconsciousness, and eventually death.

The word "hypopnea" uses combining forms of "" + "", from the Greek roots "hypo-" (meaning "low", "under", "beneath", "down", "below normal") and "pnoia" (meaning "breathing"). See pronunciation information at "dyspnea".

Hypopnea or hypopnoea is overly shallow breathing or an abnormally low respiratory rate. Hypopnea is defined by some to be less severe than apnea (the complete cessation of breathing), while other researchers have discovered hypopnea to have a "similar if not indistinguishable impact" on the negative outcomes of sleep breathing disorders. In sleep clinics, obstructive sleep apnea syndrome or obstructive sleep apnea–hypopnea syndrome is normally diagnosed based on the frequent presence of apneas and/or hypopneas rather than differentiating between the two phenomena. Hypopnea is typically defined by a decreased amount of air movement into the lungs and can cause oxygen levels in the blood to drop. It commonly is due to partial obstruction of the upper airway.

Hypopnea during sleep is classed as a sleep disorder. With moderate to severe hypopnea, sleep is disturbed such that patients may get a full night's sleep but still not feel rested because they did not get the right kind of sleep. The disruption in breathing causes a drop in blood oxygen level, which may in turn disrupt the stages of sleep.

Daytime hypopnea events, however, are mostly limited to those with severely compromised respiratory muscles, as occurs in certain neuromuscular diseases or compromised central respiratory drive, as occurs in conditions such as acquired or congenital central hypoventilation syndrome (ACHS or CCHS). Daytime hypopnea can also cause a drop in blood oxygen level.

Hypoventilation may be caused by:

- A medical condition such as stroke affecting the brainstem

- Voluntary breath-holding or underbreathing, for example, hypoventilation training or Buteyko

- Medication or drugs, typically when taken in accidental or intentional overdose. Opioids in particular are known to cause respiratory depression. Examples of opioids include pharmaceuticals such as oxycodone and hydromorphone.

- Hypocapnia, which stimulates hypoventilation

- Chronic mountain sickness, a mechanism to conserve energy.

Hypercapnia, also known as hypercarbia and CO retention, is a condition of abnormally elevated carbon dioxide (CO) levels in the blood. Carbon dioxide is a gaseous product of the body's metabolism and is normally expelled through the lungs.

Hypercapnia normally triggers a reflex which increases breathing and access to oxygen (O), such as arousal and turning the head during sleep. A failure of this reflex can be fatal, for example as a contributory factor in sudden infant death syndrome.

Hypercapnia is the opposite of hypocapnia, the state of having abnormally reduced levels of carbon dioxide in the blood. Hypercapnia is from the Greek "hyper" = "above" or "too much" and "kapnos" = "smoke".

Orofaciodigital syndrome type 1 is diagnosed through genetic testing. Some symptoms of Orofaciodigital syndrome type 1 are oral features such as, split tongue, benign tumors on the tongue, cleft palate, hypodontia and other dental abnormalities. Other symptoms of the face include hypertelorism and micrognathia. Bodily abnormalities such as webbed, short, joined, or abnormally curved fingers and toes are also symptoms of Orofaciodigital syndrome type 1. The most frequent symptoms are accessory oral frenulum, broad alveolar ridges, frontal bossing, high palate, hypertelorism, lobulated tongue, median cleft lip, and wide nasal bridge. Genetic screening of the OFD1 gene is used to officially diagnose a patient who has the syndrome, this is detected in 85% of individuals who are suspected to have Orofaciodigital syndrome type 1.

Hypoxemia (PaO2 6.0kPa).

The basic defect in type 2 respiratory failure is characterized by:

Type 2 respiratory failure is caused by inadequate alveolar ventilation; both oxygen and carbon dioxide are affected. Defined as the buildup of carbon dioxide levels (PCO) that has been generated by the body but cannot be eliminated. The underlying causes include:

- Increased airways resistance (chronic obstructive pulmonary disease, asthma, suffocation)

- Reduced breathing effort (drug effects, brain stem lesion, extreme obesity)

- A decrease in the area of the lung available for gas exchange (such as in chronic bronchitis)

- Neuromuscular problems (Guillain–Barré syndrome, motor neuron disease)

- Deformed (kyphoscoliosis), rigid (ankylosing spondylitis), or flail chest.

Respiratory failure results from inadequate gas exchange by the respiratory system, meaning that the arterial oxygen, carbon dioxide or both cannot be kept at normal levels. A drop in the oxygen carried in blood is known as hypoxemia; a rise in arterial carbon dioxide levels is called hypercapnia. Respiratory failure is classified as either Type I or Type II, based on whether there is a high carbon dioxide level. The definition of respiratory failure in clinical trials usually includes increased respiratory rate, abnormal blood gases (hypoxemia, hypercapnia, or both), and evidence of increased work of breathing.

The normal partial pressure reference values are: oxygen PaO more than , and carbon dioxide PaCO lesser than .

Orofaciodigital syndrome 1 (OFD1), also called Papillon-League and Psaume syndrome, is an X-linked congenital disorder characterized by malformations of the face, oral cavity, and digits with polycystic kidney disease and variable involvement of the central nervous system.

The symptoms of Sly syndrome are similar to those of Hurler syndrome (MPS I). The symptoms include:

- in the head, neck, and face: coarse (Hurler-like) facies and macrocephaly, frontal prominence, premature closure of sagittal lambdoid sutures, and J-shaped sella turcica

- in the eyes: corneal opacity and iris coloboma

- in the nose: anteverted nostrils and a depressed nostril bridge

- in the mouth and oral areas: prominent alveolar processes and cleft palate

- in the thorax: usually pectus carinatum or exacavatum and oar-shaped ribs; also a protruding abdomen and inguinal or umbilical hernia

- in the extremities: talipes, an underdeveloped ilium, aseptic necrosis of femoral head, and shortness of tubular bones occurs

- in the spine: kyphosis or scoliosis and hook-like deformities in thoracic and lumbar vertebrate

- in the bones: dysostosis multiplex

In addition recurrent pulmonary infections occur. Hepatomegaly occurs in the gastrointestinal system. Splenomegaly occurs in the hematopoietic system. Inborn mucopolysaccharide metabolic disorders due to β-glucuronidase deficiency with granular inclusions in granulocytes occurs in the biochemical and metabolic systems. Growth and motor skills are affected, and mental retardation also occurs.

Feeding problems are common in infants with BPD, often due to prolonged intubation. Such infants often display oral-tactile hypersensitivity (also known as oral aversion).

Physical findings:

- hypoxemia;

- hypercapnia;

- crackles, wheezing, & decreased breath sounds;

- increased bronchial secretions;

- hyperinflation;

- frequent lower respiratory infections;

- delayed growth & development;

- cor pulmonale;

- CXR shows with hyperinflation, low diaphragm, atelectasis, cystic changes.

The newer National Institute of Health (US) criteria for BPD (for neonates treated with more than 21% oxygen for at least 28 days) is as follows:,

- Mild

- Breathing room air at 36 weeks post-menstrual age or discharge (whichever comes first) for babies born before 32 weeks, or

- breathing room air by 56 days postnatal age, or discharge (whichever comes first) for babies born after 32 weeks gestation.

- Moderate

- Need for <30% oxygen at 36 weeks postmenstrual age, or discharge (whichever comes first) for babies born before 32 weeks, or

- need for <30% oxygen to 56 days postnatal age, or discharge (whichever comes first) for babies born after 32 weeks gestation.

- Severe

- Need for >30% oxygen, with or without positive pressure ventilation or continuous positive pressure at 36 weeks postmenstrual age, or discharge (whichever comes first) for babies born before 32 weeks, or

- need for >30% oxygen with or without positive pressure ventilation or continuous positive pressure at 56 days postnatal age, or discharge (whichever comes first) for babies born after 32 weeks' gestation.

In an acute context, hypoxemia can cause symptoms such as those in respiratory distress. These include breathlessness, an increased rate of breathing, use of the chest and abdominal muscles to breathe, and lip pursing.

Chronic hypoxemia may be compensated or uncompensated. The compensation may cause symptoms to be overlooked initially, however, further disease or a stress such as any increase in oxygen demand may finally unmask the existing hypoxemia. In a compensated state, blood vessels supplying less-ventilated areas of the lung may selectively contract, to redirect the blood to areas of the lungs which are better ventilated. However, in a chronic context, and if the lungs are not well ventilated generally, this mechanism can result in pulmonary hypertension, overloading the right ventricle of the heart and causing cor pulmonale and right sided heart failure. Polycythemia can also occur. In children, chronic hypoxemia may manifest as delayed growth, neurological development and motor development and decreased sleep quality with frequent sleep arousals.

Other symptoms of hypoxemia may include cyanosis, digital clubbing, and symptoms that may relate to the cause of the hypoxemia, including cough and hemoptysis.

Serious hypoxemia occurs (1) when the partial pressure of oxygen in blood is less than 60 mm Hg, (the beginning of the steep portion of the oxygen–haemoglobin dissociation curve, where a small decrease in the partial pressure of oxygen results in a large decrease in the oxygen content of the blood); or (2) when hemoglobin oxygen saturation is less than 90%. Severe hypoxia can lead to respiratory failure

A variety of conditions that physically limit airflow can lead to hypoxemia.

- Suffocation, including temporary interruption temporary cessation of breathing as in obstructive sleep apnea, or bedclothes may interfere with breathing in infants, a putative cause of SIDS.

- Structural deformities of the chest, such as scoliosis and kyphosis, which can restrict breathing and lead to hypoxia.

- Muscle weakness, which may limit the ability of the diaphragm, the primary muscle for drawing new air into lungs, to function. This may be a result of a congenital disease, such as motor neuron disease, or an acquired condition, such as fatigue in severe cases of COPD.

Ventilation Perfusion mismatch or "V/Q defects" are defects in total lung ventilation perfusion ratio. It is a condition in which one or more areas of the lung receive oxygen but no blood flow, or they receive blood flow but no oxygen due to some diseases and disorders.

The V/Q ratio of a healthy lung is approximately equal to 0.8, as normal lungs are not perfectly matched., which means the rate of alveolar ventilation to the rate of pulmonary blood flow is roughly equal.

The ventilation perfusion ratio can be measured by measuring the A-a gradient i.e. the alveolar-arterial gradient.

The signs and symptoms of ARDS often begin within two hours of an inciting event, but can occur after 1–3 days. Signs and symptoms may include shortness of breath, fast breathing, and a low oxygen level in the blood due to abnormal ventilation.