ROHHAD

Last updated
ROHHAD
Other namesROHHADNET
Haven ROHHAD.jpg
A photograph of a child who has been diagnosed with ROHHAD
Symptoms rapid onset obesity, hypothalamic dysfunction, hypoventilation, autonomic dysfunction, neuroendocrine tumors, behavior problems
Usual onset1.5-11 years of age
Causesunknown
Prognosis Life Limiting
Frequency158 cases reported worldwide

Rapid-onset obesity with hypothalamic dysregulation, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare condition whose etiology is currently unknown. [1] ROHHAD mainly affects the endocrine system and autonomic nervous system, but patients can exhibit a variety of signs. Patients present with both alveolar hypoventilation along with hypothalamic dysfunction, which distinguishes ROHHAD from congenital central hypoventilation syndrome (CCHS). [2] ROHHAD is a rare disease, with only 100 reported cases worldwide thus far. [3]

Contents

The first sign of ROHHAD is a rapid weight gain between 1.5 and 11 years of age. [4] Typically, hypoventilation, or abnormally slow breathing, presents after the rapid onset obesity. [4] Symptoms of hypothalamic dysfunction and autonomic dysfunction present in a variety of ways, but in order for a diagnosis of ROHHAD they must be present in some form. [3] Approximately 40% of patients will develop neuroendocrine tumors. [1] There is also a possibility of behavioral disorders, but some children with ROHHAD have normal cognitive development and intelligence. [3]

Treatment plans for ROHHAD vary depending on each patient's symptoms. There is no cure, so treatment is geared toward managing the symptoms that each patient manifests. [5] ROHHAD is fatal in 50-60% of cases when undiagnosed and untreated, due to cardiopulmonary arrest secondary to untreated hypoventilation. [4] The earlier the disease is diagnosed and treatment starts, the better a child's prognosis is. [5]

Signs and symptoms

Rapid-onset Obesity

The rapid onset obesity aspect of ROHHAD is usually the first diagnostic indicator of the disease. Patients often present with hyperphagia and rapid weight gain. This rapid weight gain is defined as 20-30 pounds over a 6-12 month period, and typically occurs between the ages of 1.5 and 11. [4]

Hypothalamic dysfunction

Hypothalamic dysfunction refers to the hypothalamus, which is a structure within the brain which participates in regulating the pituitary gland, autonomic nervous system, and endocrine system. [6] Symptoms related to hypothalamic dysfunction may include abnormal sodium balance (hyponatremia or hypernatremia), high progestin levels, low cortisol levels, delayed or early-onset puberty, and low thyroid hormone. [3] Patients will also often experience a decelerated growth rate throughout childhood. [7]

Sodium imbalance within the body can have severe symptoms and be potentially life-threatening if not controlled. Hyponatremia, or low sodium levels, can cause symptoms such as nausea, headache, seizures, or even cause patients to become comatose. [8] Hypernatremia, or high sodium levels in the blood, can cause nausea, muscle weakness, altered mental status, or coma. [9] Irregular temperature regulation and diabetes insipidus are also possible symptoms of hypothalamic dysfunction. [10]

ROHHAD patients develop these symptoms at varying ages and in varying numbers, but all patients will develop some symptoms of hypothalamic dysfunction. [3]

Hypoventilation

Symptoms of hypoventilation and breathing malfunctions typically present after the rapid weight gain. Some patients may initially develop obstructive sleep apnea, which is common in obese children. [3] Obstructive sleep apnea is the most common form of sleep apnea, and causes breathing to abruptly stop and begin again during sleep. This is caused by throat muscles relaxing during sleep and blocking the airway, and is typically noticed as patients will snore loudly throughout the night. [11] Every patient diagnosed with ROHHAD develops alveolar hypoventilation, regardless of whether they presented with sleep apnea. [3] Alveolar hypoventilation is a condition in which patients have very low blood oxygen levels and shallow breathing. In healthy patients, when blood oxygen levels are low, the brain sends a signal to breathe and bring more oxygen to the blood. In ROHHAD patients, this reaction does not occur. [12] This condition is usually only present during sleep, however in more severely affected patients shallow breathing may continue throughout the day. Hypoventilation can go unnoticed until cardiopulmonary arrest, which is why ROHHAD has the potential to be a fatal disease. [3] Ventilatory support is required for patients during sleep, however it is only needed during waking hours for those most severely affected (about 50% of patients). [3] [10]

Autonomic Dysfunction

Autonomic dysfunction refers to the autonomic nervous system, which is responsible for regulating internal processes without conscious intervention. [13] This may involve abnormalities in cardiac rhythm, temperature regulation, digestion, and eye movements. Not all ROHHAD patients will experience all of these symptoms, however they will have at least some of these issues. [3] Examples of autonomic dysfunction include hyperthermia, hypothermia, pupillary dysfunction, strabismus, chronic constipation, and chronic diarrhea. [7]

Neuroendocrine tumors

Approximately 40% of ROHHAD patients will develop tumors originating in the neural crest. [1] These tumors are typically classified as ganglioneuroma or ganglioneuroblastomas. [7] These tumors are not believed to significantly worsen or contribute to the prognosis of ROHHAD. [14] It was suggested that ROHHAD be renamed ROHHADNET in order to include these tumors in the diagnostic criteria, but this has only been adopted for patients who develop these tumors. [3] [15]

Behavioral issues

Some children diagnosed with ROHHAD may also present with behavioral disorders and/or intellectual disability, [16] however this is believed to be a result of low oxygen levels secondary to hypoventilation during childhood development. The later ROHHAD is diagnosed, the greater the risk for behavioral problems due to hypoxia from hypoventilation or during cardiopulmonary arrest. [3]

Cause

The etiology of ROHHAD is currently unknown, and the condition is diagnosed based on a set of clinical criteria. [1] It is believed that there may be a genetic component to ROHHAD, however there is no widely accepted gene linked to the disease. [3] There has been one ROHHAD patient identified to have a mutation in the retinoic acid-induced 1(RAI1) gene through Whole Exome Sequencing, but there has been no otherwise proven link between the RAI1 gene and ROHHAD. [17]

It is believed that ROHHAD originates from a combination of genetic and environmental or immunological factors. [1] As of yet, evidence of its etiology has not been discovered and is not well understood. [1]

In 2011, a case of monozygotic twins with divergent ROHHAD phenotypes was reported. One twin was affected with ROHHAD and developed symptoms, while the other twin developed normally. This report questioned the theory that ROHHAD is genetically inherited, and the authors suggest that the disease may have an autoimmune or epigenetic etiology. [18]

Pathophysiology

The pathophysiology of ROHHAD is not currently known or understood. [1]

Diagnosis

Rapid obesity is the first symptom to arise between the ages of 1.5 and 11. This is typically followed by hypoventilation, which if left untreated, can result in fatal cardiorespiratory arrest. [4] This is why early diagnosis has proven to be imperative for ROHHAD patients, and it has been suggested that ROHHAD be considered in every isolated case of early rapid-onset obesity. [7] Early diagnosis is also vital in maintaining electrolyte and hormone balances caused by hypothalamic dysfunction in order to promote healthy development and prevent further problems. [14]

As the symptoms of ROHHAD are so diverse and the condition is so rare, the disease is often misdiagnosed as Cushing's disease or Congenital Central Hypoventilation Syndrome when it first presents in patients. [7]

Prevention

As the cause of ROHHAD is unknown, there is no way to prevent onset of the disease. [16]

Management

There is no known cure for ROHHAD, therefore treatment for the disease involves managing symptoms as they manifest in the patient. As not all ROHHAD patients develop the same symptoms, treatment plans vary between patients. Proper treatment of hypothalamic dysfunction and hypoventilation is the most critical aspect of ROHHAD management, as these symptoms have the greatest ability to cause death or behavioral problems if left uncontrolled. [5]

Rapid onset obesity treatment

Attempting to control weight through diet and exercise can be exceedingly difficult in patients with ROHHAD due to a number of factors. Encouraging ROHHAD patients to exercise vigorously can be dangerous, as their breathing will not increase with exertion and this can cause hypoxia. Therefore, it is important for ROHHAD patients to exercise at a moderate intensity and for their oxygen levels to be monitored throughout. Typically, the obesity associated with ROHHAD is managed by preventing further weight gain as the child grows. [3]

Hypothalamic dysfunction treatment

Treatment for hypothalamic dysfunction is tailored to each patient's needs, as there is no set of hypothalamic symptoms that all ROHHAD patients will manifest. All ROHHAD patients should be evaluated by a pediatric endocrinologist in order to determine a treatment plan for hypothalamic dysfunction.[ citation needed ]

Patients may be given human growth hormone to treat stunted growth, or hormone replacement to treat any hormone deficiencies. Often patients are placed on a strict fluid regimen to treat for imbalances such as hyponatremia or hypernatremia. [3] Patients who present with diabetes insipidus may also be treated with desmopressin, a synthetic replacement for anti-diuretic hormone. [19]

Hypoventilation treatment

Every ROHHAD patient requires some form of ventilatory support, ranging from non-invasive BiPAP machines to tracheostomy procedures. Approximately 50% of ROHHAD patients will require ventilatory support day and night, whereas the other half only require night-time support. [1]

A bilevel positive airway pressure machine, or BiPAP, is a ventilator mask worn at night. The BiPAP pushes air into the lungs, therefore breathing for the patient. [20] This is helpful for ROHHAD patients, as hypoventilation causes the mechanism that controls breathing in oxygen to slow and sometimes stop during sleep.[ citation needed ]

A tracheostomy is the result of a surgical procedure to create a hole in the trachea in order to give access to ventilatory tubing. This procedure is performed to create an airway in situations when long term continuous use of a ventilator is needed. [21] ROHHAD patients whose hypoventilation is so severe that they require support during the day and night will often undergo tracheostomies. [10]

Autonomic dysfunction treatment

Treatment for autonomic dysfunction varies greatly on the severity of the dysfunction and the type. Many patients with ROHHAD experience strabismus, which is a weakness in eye muscle causing a "cross-eyed" effect. This can be treated with glasses, eye muscle exercises, or even surgery. [22] ROHHAD patients also often experience bradycardia, or low heart rate. This may require a cardiac pacemaker be placed in order to regulate heartbeat. [23] Gastrointestinal problems, such as constipation or diarrhea, are often treated on an as-needed basis with laxatives or dietary changes. It is also important that ambient temperatures are monitored in patients who have temperature regulation issues such as hyperthermia or hypothermia. [3]

Neuroendocrine tumor treatment

Tumors of neural crest origin develop in approximately 40% of patients. These are typically ganglioneuromas or ganglioneuroblastomas. Neural crest tumors have the ability to form in multiple organs tissues throughout the body, typically in the chest or abdomen. [24] It is therefore important for ROHHAD patients to have regular MRI and CT scans to screen for tumor growth. [7] It is believed that these tumors do not significantly affect the prognosis for ROHHAD patients. [14] Neuroendocrine tumors can arise 7–16 years after the initial onset of symptoms, therefore the name ROHHADNET (which includes these tumors) has not been widely accepted as it is believed this name would lead to further misdiagnosis. Treatment for these neuroendocrine tumors requires surgical removal, typically performed by a pediatric oncologist. [3]

Prognosis

The most dangerous and fatal aspect of ROHHAD is the potential for cardiopulmonary arrest if hypoventilation is not found and treated in a timely manner. Approximately 50 to 60% of ROHHAD patients die due to cardiopulmonary arrest. [4] The earlier symptoms are identified and patients are diagnosed, the more positive their outcomes are. [1]

It has been found that children who are diagnosed earlier in life and received treatment for hypoventilation and hypothalamic dysfunction (fluid imbalances, etc.) are less likely to develop behavioral issues or experience sudden cardiorespiratory arrest later in life. [5]

Research

A group at Ann & Robert H. Lurie Children's Hospital of Chicago has an international repository for patients with ROHHAD, which is available to researchers who are interested in the disease. [25]

As of June 2018, there are 3 clinical trials currently recruiting patients with ROHHAD being performed respectively at Lurie Children's Hospital, Sidney Kimmel Cancer Center, and Boston Children's Hospital. [26]

Epidemiology

There have been at least 158 documented cases of ROHHAD worldwide. [27]

History

ROHHAD was first described in 1965, and this was believed to be the first reported instance of hypoventilation presenting alongside hypothalamic dysfunction. [2]

ROHHAD had often been mistaken for congenital central hypoventilation syndrome, until the distinction was made by Ize-Ludlow et al. in 2007. These conditions are now permanently differentiated from one other, as patients with CCHS have mutations in the PHOX2B gene, whereas ROHHAD patients do not. [28]

Society and culture

The ROHHAD Association is an organization that aims to increase awareness for ROHHAD and promote research opportunities. They also organized fundraisers and events in order to give to researchers and promote visibility of ROHHAD. [29] ROHHAD Fight Inc is a charity that was created for Marisa, a child who was diagnosed with ROHHAD, with the goal of raising awareness for the condition. [30]

See also

Related Research Articles

<span class="mw-page-title-main">Sleep apnea</span> Disorder involving pauses in breathing during sleep

Sleep apnea, also spelled sleep apnoea, is a sleep disorder in which pauses in breathing or periods of shallow breathing during sleep occur more often than normal. Each pause can last for a few seconds to a few minutes and they happen many times a night. In the most common form, this follows loud snoring. A choking or snorting sound may occur as breathing resumes. Because the disorder disrupts normal sleep, those affected may experience sleepiness or feel tired during the day. In children, it may cause hyperactivity or problems in school.

<span class="mw-page-title-main">Sleep disorder</span> Medical disorder of a persons sleep patterns

A sleep disorder, or somnipathy, is a medical disorder of an individual's sleep patterns. Some sleep disorders are severe enough to interfere with normal physical, mental, social and emotional functioning. Sleep disorders are frequent and can have serious consequences on patients’ health and quality of life. Polysomnography and actigraphy are tests commonly ordered for diagnosing sleep disorders.

<span class="mw-page-title-main">Autonomic neuropathy</span> Medical condition

Autonomic neuropathy is a form of polyneuropathy that affects the non-voluntary, non-sensory nervous system, affecting mostly the internal organs such as the bladder muscles, the cardiovascular system, the digestive tract, and the genital organs. These nerves are not under a person's conscious control and function automatically. Autonomic nerve fibers form large collections in the thorax, abdomen, and pelvis outside the spinal cord. They have connections with the spinal cord and ultimately the brain, however. Most commonly autonomic neuropathy is seen in persons with long-standing diabetes mellitus type 1 and 2. In most—but not all—cases, autonomic neuropathy occurs alongside other forms of neuropathy, such as sensory neuropathy.

<span class="mw-page-title-main">Obesity hypoventilation syndrome</span> Condition in which severely overweight people fail to breathe rapidly or deeply enough

Obesity hypoventilation syndrome (OHS) is a condition in which severely overweight people fail to breathe rapidly or deeply enough, resulting in low oxygen levels and high blood carbon dioxide (CO2) levels. The syndrome is often associated with obstructive sleep apnea (OSA), which causes periods of absent or reduced breathing in sleep, resulting in many partial awakenings during the night and sleepiness during the day. The disease puts strain on the heart, which may lead to heart failure and leg swelling.

Cushing's disease is one cause of Cushing's syndrome characterised by increased secretion of adrenocorticotropic hormone (ACTH) from the anterior pituitary. This is most often as a result of a pituitary adenoma or due to excess production of hypothalamus CRH that stimulates the synthesis of cortisol by the adrenal glands. Pituitary adenomas are responsible for 80% of endogenous Cushing's syndrome, when excluding Cushing's syndrome from exogenously administered corticosteroids. The equine version of this disease is Pituitary pars intermedia dysfunction.

<span class="mw-page-title-main">Dysautonomia</span> Any disease or malfunction of the autonomic nervous system

Dysautonomia, autonomic failure, or autonomic dysfunction is a condition in which the autonomic nervous system (ANS) does not work properly. This may affect the functioning of the heart, bladder, intestines, sweat glands, pupils, and blood vessels. Dysautonomia has many causes, not all of which may be classified as neuropathic. A number of conditions can feature dysautonomia, such as Parkinson's disease, multiple system atrophy, dementia with Lewy bodies, Ehlers–Danlos syndromes, autoimmune autonomic ganglionopathy and autonomic neuropathy, HIV/AIDS, mitochondrial cytopathy, pure autonomic failure, autism, and postural orthostatic tachycardia syndrome.

Hypoventilation occurs when ventilation is inadequate to perform needed respiratory gas exchange. By definition it causes an increased concentration of carbon dioxide (hypercapnia) and respiratory acidosis. Hypoventilation is not synonymous with respiratory arrest, in which breathing ceases entirely and death occurs within minutes due to hypoxia and leads rapidly into complete anoxia, although both are medical emergencies. Hypoventilation can be considered a precursor to hypoxia and its lethality is attributed to hypoxia with carbon dioxide toxicity.

Anovulation is when the ovaries do not release an oocyte during a menstrual cycle. Therefore, ovulation does not take place. However, a woman who does not ovulate at each menstrual cycle is not necessarily going through menopause. Chronic anovulation is a common cause of infertility.

Hypersomnia is a neurological disorder of excessive time spent sleeping or excessive sleepiness. It can have many possible causes and can cause distress and problems with functioning. In the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), hypersomnolence, of which there are several subtypes, appears under sleep-wake disorders.

<span class="mw-page-title-main">Central hypoventilation syndrome</span> Medical condition

Central hypoventilation syndrome (CHS) is a sleep-related breathing disorder that causes ineffective breathing, apnea, or respiratory arrest during sleep. CHS can either be congenital (CCHS) or acquired (ACHS) later in life. The condition can be fatal if untreated. CCHS was once known as Ondine's curse.

<span class="mw-page-title-main">Hyperandrogenism</span> Medical condition

Hyperandrogenism is a medical condition characterized by high levels of androgens. It is more common in women than men. Symptoms of hyperandrogenism may include acne, seborrhea, hair loss on the scalp, increased body or facial hair, and infrequent or absent menstruation. Complications may include high blood cholesterol and diabetes. It occurs in approximately 5% of women of reproductive age.

<span class="mw-page-title-main">Obstructive sleep apnea</span> Sleeping and breathing disorder

Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder and is characterized by recurrent episodes of complete or partial obstruction of the upper airway leading to reduced or absent breathing during sleep. These episodes are termed "apneas" with complete or near-complete cessation of breathing, or "hypopneas" when the reduction in breathing is partial. In either case, a fall in blood oxygen saturation, a disruption in sleep, or both, may result. A high frequency of apneas or hypopneas during sleep may interfere with the quality of sleep, which – in combination with disturbances in blood oxygenation – is thought to contribute to negative consequences to health and quality of life. The terms obstructive sleep apnea syndrome (OSAS) or obstructive sleep apnea–hypopnea syndrome (OSAHS) may be used to refer to OSA when it is associated with symptoms during the daytime.

Kleine–Levin syndrome (KLS) is a rare neurological disorder characterized by persistent episodic hypersomnia accompanied by cognitive and behavioral changes. These changes may include disinhibition, sometimes manifested through hypersexuality, hyperphagia or emotional lability, and other symptoms, such as derealization. Patients generally experience recurrent episodes of the condition for more than a decade, which may return at a later age. Individual episodes generally last more than a week, sometimes lasting for months. The condition greatly affects the personal, professional, and social lives of those with KLS. The severity of symptoms and the course of the syndrome vary between those with KLS. Patients commonly have about 20 episodes over about a decade. Several months may elapse between episodes.

Hypopnea is overly shallow breathing or an abnormally low respiratory rate. Hypopnea is defined by some to be less severe than apnea, 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.

The International Classification of Sleep Disorders (ICSD) is "a primary diagnostic, epidemiological and coding resource for clinicians and researchers in the field of sleep and sleep medicine". The ICSD was produced by the American Academy of Sleep Medicine (AASM) in association with the European Sleep Research Society, the Japanese Society of Sleep Research, and the Latin American Sleep Society. The classification was developed as a revision and update of the Diagnostic Classification of Sleep and Arousal Disorders (DCSAD) that was produced by both the Association of Sleep Disorders Centers (ASDC) and the Association for the Psychophysiological Study of Sleep and was published in the journal Sleep in 1979. A second edition, called ICSD-2, was published by the AASM in 2005. The third edition, ICSD-3, was released by the AASM in 2014. A text revision of the third edition (ICSD-3-TR) was published in 2023 by the AASM.

Paroxysmal nocturnal dyspnea or paroxysmal nocturnal dyspnoea (PND) is an attack of severe shortness of breath and coughing that generally occurs at night. It usually awakens the person from sleep, and may be quite frightening. PND, as well as simple orthopnea, may be relieved by sitting upright at the side of the bed with legs dangling, as symptoms typically occur when the person is recumbent, or lying down.

Central sleep apnea (CSA) or central sleep apnea syndrome (CSAS) is a sleep-related disorder in which the effort to breathe is diminished or absent, typically for 10 to 30 seconds either intermittently or in cycles, and is usually associated with a reduction in blood oxygen saturation. CSA is usually due to an instability in the body's feedback mechanisms that control respiration. Central sleep apnea can also be an indicator of Arnold–Chiari malformation.

A sleep-related breathing disorder is a sleep disorder in which abnormalities in breathing occur during sleep that may or may not be present while awake. According to the International Classification of Sleep Disorders, sleep-related breathing disorders are classified as follows:

Classification of sleep disorders comprises systems for classifying medical disorders associated with sleep. Systems have changed, increasingly using technological discoveries to advance the understanding of sleep and recognition of sleep disorders.

Infantile apnea is a rare disease that is characterized by cessation of breathing in an infant for at least 20 seconds or a shorter respiratory pause that is associated with a slow heart rate, bluish discolouration of the skin, extreme paleness, gagging, choking and/or decreased muscle tone. Infantile apnea occurs in children under the age of one and it is more common in premature infants. Symptoms of infantile apnea occur most frequently during the rapid eye movement (REM) stage of sleep. The nature and severity of breathing problems in patients can be detected in a sleep study called a polysomnography which measures the brain waves, heartbeat, body movements and breathing of a patient overnight. Infantile apnea can be caused by developmental problems that result in an immature brainstem or it can be caused other medical conditions. As children grow and develop, infantile apnea usually does not persist. Infantile apnea may be related to some cases of sudden infant death syndrome (SIDS) however, the relationship between infantile apnea and SIDS is not known.

References

  1. 1 2 3 4 5 6 7 8 9 Ibáñez-Micó, S.; Marcos Oltra, A.M.; De Murcia Lemauviel, S.; Ruiz Pruneda, R.; Martínez Ferrández, C.; Domingo Jiménez, R. (2017-11-01). "Rapid-onset obesity with hypothalamic dysregulation, hypoventilation, and autonomic dysregulation (ROHHAD syndrome): A case report and literature review". Neurología (English Edition). 32 (9): 616–622. doi: 10.1016/j.nrleng.2016.04.003 . ISSN   2173-5808. PMID   27340018.
  2. 1 2 FISHMAN, L. S. (1965-08-01). "Primary Alveolar Hypoventilation Syndrome (Ondine's Curse)". American Journal of Diseases of Children. 110 (2): 155–61. doi:10.1001/archpedi.1965.02090030165011. ISSN   0002-922X. PMID   14320765.
  3. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 "Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation - NORD (National Organization for Rare Disorders)". NORD (National Organization for Rare Disorders). Retrieved 2018-06-03.
  4. 1 2 3 4 5 6 Reppucci, Diana; Hamilton, Jill; Yeh, E Ann; Katz, Sherri; Al-Saleh, Suhail; Narang, Indra (2016-07-30). "ROHHAD syndrome and evolution of sleep disordered breathing". Orphanet Journal of Rare Diseases. 11 (1): 106. doi: 10.1186/s13023-016-0484-1 . ISSN   1750-1172. PMC   4967322 . PMID   27473663.
  5. 1 2 3 4 Weese-Mayer, Debra E.; Rand, Casey M.; Ize-Ludlow, Diego (August 2013). "Commentary: Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD): Remember Your ABCs (Airway, Breathing, Circulation)". Journal of the Canadian Academy of Child and Adolescent Psychiatry. 22 (3): 238–239. ISSN   1719-8429. PMC   3749899 . PMID   23970914.
  6. ↑ "hypothalamus | Definition, Anatomy, & Function". Encyclopedia Britannica. Retrieved 2018-06-03.
  7. 1 2 3 4 5 6 Bougnères, Pierre; Pantalone, Letitia; Linglart, Agnès; Rothenbühler, Anya; Le Stunff, Catherine (October 2008). "Endocrine Manifestations of the Rapid-Onset Obesity with Hypoventilation, Hypothalamic, Autonomic Dysregulation, and Neural Tumor Syndrome in Childhood". The Journal of Clinical Endocrinology & Metabolism. 93 (10): 3971–3980. doi: 10.1210/jc.2008-0238 . ISSN   0021-972X. PMID   18628522.
  8. ↑ "Hyponatremia - Symptoms and causes". Mayo Clinic. Retrieved 2018-06-08.
  9. ↑ Reynolds, Rebecca M; Padfield, Paul L; Seckl, Jonathan R (2006-03-25). "Disorders of sodium balance". BMJ: British Medical Journal. 332 (7543): 702–705. doi:10.1136/bmj.332.7543.702. ISSN   0959-8138. PMC   1410848 . PMID   16565125.
  10. 1 2 3 Philadelphia, The Children's Hospital of (2016-08-24). "ROHHAD: Rapid-onset Obesity, Breathing and Behavioral Issues Indicate a Very Sick Patient". www.chop.edu. Retrieved 2018-06-03.
  11. ↑ "Obstructive sleep apnea - Symptoms and causes". Mayo Clinic. Retrieved 2018-06-06.
  12. ↑ "Primary alveolar hypoventilation". Scripps Health. 2008-08-28. Retrieved 2018-06-06.
  13. ↑ "autonomic nervous system | Divisions & Functions". Encyclopedia Britannica. Retrieved 2018-06-06.
  14. 1 2 3 Pontual, Loic De; Trochet, Delphine; Caillat-Zucman, Sophie; Shenab, Othman A Abou; Bougneres, Pierre; Crow, Yanick; Cunningham, Steve; Esteva, Blandine; Heberle, Lada Cindro (December 2008). "Delineation of Late Onset Hypoventilation Associated with Hypothalamic Dysfunction Syndrome". Pediatric Research. 64 (6): 689–694. doi: 10.1203/PDR.0b013e318187dd0e . ISSN   0031-3998. PMID   18670370.
  15. ↑ Kocaay, Pınar; Şıklar, Zeynep; Çamtosun, Emine; Kendirli, Tanıl; Berberoğlu, Merih (December 2014). "ROHHAD Syndrome: Reasons for Diagnostic Difficulties in Obesity". Journal of Clinical Research in Pediatric Endocrinology. 6 (4): 254–257. doi:10.4274/jcrpe.1432. ISSN   1308-5727. PMC   4293662 . PMID   25541898.
  16. 1 2 "ROHHAD | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2018-06-03.
  17. ↑ Thaker, Vidhu V.; Esteves, Kristyn M.; Towne, Meghan C.; Brownstein, Catherine A.; James, Philip M.; Crowley, Laura; Hirschhorn, Joel N.; Elsea, Sarah H.; Beggs, Alan H. (May 2015). "Whole exome sequencing identifies RAI1 mutation in a morbidly obese child diagnosed with ROHHAD syndrome". The Journal of Clinical Endocrinology and Metabolism. 100 (5): 1723–1730. doi:10.1210/jc.2014-4215. ISSN   1945-7197. PMC   4422892 . PMID   25781356.
  18. ↑ Patwari, Pallavi P.; Rand, Casey M.; Berry-Kravis, Elizabeth M.; Ize-Ludlow, Diego; Weese-Mayer, Debra E. (2011-09-01). "Monozygotic Twins Discordant for ROHHAD Phenotype". Pediatrics. 128 (3): e711–e715. doi:10.1542/peds.2011-0155. ISSN   0031-4005. PMID   21807698. S2CID   21582413.
  19. ↑ "Diabetes insipidus - Diagnosis and treatment - Mayo Clinic". www.mayoclinic.org. Retrieved 2018-06-10.
  20. ↑ "BiPap | Johns Hopkins Medicine Health Library". www.hopkinsmedicine.org. Retrieved 2018-06-08.
  21. ↑ "Tracheostomy - Mayo Clinic". www.mayoclinic.org. Retrieved 2018-06-08.
  22. ↑ "Strabismus — AAPOS". www.aapos.org. Retrieved 2018-06-08.
  23. ↑ "Bradycardia - Symptoms and causes". Mayo Clinic. Retrieved 2018-06-08.
  24. ↑ Maguire, Lillias H.; Thomas, Alyssa R.; Goldstein, Allan M. (March 2015). "Tumors of the neural crest: Common themes in development and cancer". Developmental Dynamics. 244 (3): 311–322. doi: 10.1002/dvdy.24226 . ISSN   1097-0177. PMID   25382669. S2CID   28061889.
  25. ↑ "ROHHAD Research - ROHHAD Association". ROHHAD Association. Retrieved 2018-06-19.
  26. ↑ "Search of: ROHHAD - List Results - ClinicalTrials.gov" . Retrieved 2018-06-19.
  27. ↑ Harvengt J, Gernay C, Mastouri M, Farhat N, Lebrethon MC, Seghaye MC, Bours V (July 2020). "ROHHAD(NET) Syndrome: Systematic Review of the Clinical Timeline and Recommendations for Diagnosis and Prognosis". J. Clin. Endocrinol. Metab. 105 (7): 2119–2131. doi: 10.1210/clinem/dgaa247 . hdl: 2268/247972 . PMID   32407531.
  28. ↑ Ize-Ludlow, Diego; Gray, Juliette A.; Sperling, Mark A.; Berry-Kravis, Elizabeth M.; Milunsky, Jeff M.; Farooqi, I. Sadaf; Rand, Casey M.; Weese-Mayer, Debra E. (July 2007). "Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation presenting in childhood". Pediatrics. 120 (1): e179–188. doi:10.1542/peds.2006-3324. ISSN   1098-4275. PMID   17606542. S2CID   6244907.
  29. ↑ "About Us - ROHHAD Association". ROHHAD Association. Retrieved 2018-06-19.
  30. ↑ "Home". www.rohhadfight.org. Retrieved 2018-06-19.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.