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{{Infobox medical condition (new)
{{Infobox medical condition
| name           = ROHHAD
| name = ROHHAD
| synonyms        = ROHHADNET
| image = <!-- No image available -->
| image           = Haven ROHHAD.jpg
| caption = <!-- No caption available -->
| alt            =  
| field = [[Endocrinology]], [[Pediatrics]]
| caption         = A photograph of a child who has been diagnosed with ROHHAD
| symptoms = Rapid-onset obesity, hypoventilation, hypothalamic dysfunction, autonomic dysregulation
| pronounce      =
| onset = Childhood
| field           =  
| duration = Chronic
| symptoms       = rapid onset obesity, hypothalamic and autonomic dysfunction, hypoventilation etc.
| causes = Unknown
| complications  =
| risks = Genetic predisposition
| onset           =1.5-11 years of age
| diagnosis = Clinical evaluation, genetic testing
| duration       =
| treatment = Symptomatic management
| types          =  
| prognosis = Variable
| causes         = unknown
| frequency = Rare
| risks           =  
| diagnosis       =
| differential    =
| prevention      =  
| treatment       =
| medication      =  
| prognosis       = Life Limiting
| frequency       = 100 cases reported worldwide
| deaths          =
}}
}}
'''Rapid-onset obesity with hypothalamic dysregulation, hypoventilation, and autonomic dysregulation''' '''(ROHHAD)''' is a rare condition whose etiology is currently unknown.<ref name=":5" /> 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).<ref name=":8" /> ROHHAD is a rare disease, with only 100 reported cases worldwide thus far.<ref name=":0" />


The first sign of ROHHAD is a rapid weight gain between 1.5 and 11 years of age.<ref name=":1" /> Typically, hypoventilation, or abnormally slow breathing, presents after the rapid onset obesity.<ref name=":1" /> 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.<ref name=":0" /> Approximately 40% of patients will develop neuroendocrine tumors.<ref name=":5" /> There is also a possibility of behavioral disorders, but some children with ROHHAD have normal cognitive development and intelligence.<ref name=":0" />
'''ROHHAD''' is an acronym for '''Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation'''. It is a rare and complex pediatric disorder characterized by a constellation of symptoms that typically begin in early childhood. The etiology of ROHHAD is currently unknown, and it presents significant challenges in diagnosis and management.


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.<ref name=":7" /> ROHHAD is fatal in 50-60% of cases when undiagnosed and untreated, due to cardiopulmonary arrest secondary to untreated hypoventilation.<ref name=":1" /> The earlier the disease is diagnosed and treatment starts, the better a child's prognosis is.<ref name=":7" />
==Clinical Features==
ROHHAD syndrome is marked by a distinct set of clinical features:


== Signs & symptoms ==
===Rapid-onset Obesity===
Children with ROHHAD experience a sudden and dramatic increase in weight, often over a period of 6 to 12 months. This rapid weight gain is not associated with changes in diet or physical activity levels and is one of the earliest signs of the disorder.


=== Rapid-onset Obesity ===
===Hypothalamic Dysfunction===
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.<ref name=":1">{{Cite journal|last=Reppucci|first=Diana|last2=Hamilton|first2=Jill|last3=Yeh|first3=E Ann|last4=Katz|first4=Sherri|last5=Al-Saleh|first5=Suhail|last6=Narang|first6=Indra|date=2016-07-30|title=ROHHAD syndrome and evolution of sleep disordered breathing|journal=Orphanet Journal of Rare Diseases|volume=11|issue=1|pages=106|doi=10.1186/s13023-016-0484-1|issn=1750-1172|pmc=4967322|pmid=27473663}}</ref>
The [[hypothalamus]] is a critical brain region involved in regulating various bodily functions, including hunger, thirst, sleep, and temperature. In ROHHAD, hypothalamic dysfunction can lead to:
* [[Hyperphagia]]
* [[Polydipsia]]
* [[Sleep disturbances]]
* [[Thermoregulatory instability]]


=== Hypothalamic dysfunction ===
===Hypoventilation===
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]].<ref>{{Cite news|url=https://www.britannica.com/science/hypothalamus|title=hypothalamus {{!}} Definition, Anatomy, & Function|work=Encyclopedia Britannica|access-date=2018-06-03}}</ref> 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.<ref name=":0">{{Cite news|url=https://rarediseases.org/rare-diseases/rapid-onset-obesity-with-hypothalamic-dysfunction-hypoventilation-and-autonomic-dysregulation/|title=Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation - NORD (National Organization for Rare Disorders)|work=NORD (National Organization for Rare Disorders)|access-date=2018-06-03}}</ref> Patients will also often experience a decelerated growth rate throughout childhood.<ref name=":4" />
Hypoventilation refers to inadequate ventilation leading to elevated levels of carbon dioxide in the blood. In ROHHAD, this can manifest as:
* [[Sleep apnea]]
* Daytime hypoventilation
* Respiratory failure


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.<ref>{{Cite news|url=https://www.mayoclinic.org/diseases-conditions/hyponatremia/symptoms-causes/syc-20373711|title=Hyponatremia - Symptoms and causes|work=Mayo Clinic|access-date=2018-06-08}}</ref> Hypernatremia, or high sodium levels in the blood, can cause nausea, muscle weakness, altered mental status, or coma.<ref>{{Cite journal|last=Reynolds|first=Rebecca M|last2=Padfield|first2=Paul L|last3=Seckl|first3=Jonathan R|date=2006-03-25|title=Disorders of sodium balance|journal=BMJ : British Medical Journal|volume=332|issue=7543|pages=702–705|issn=0959-8138|pmc=1410848|pmid=16565125|doi=10.1136/bmj.332.7543.702}}</ref> Irregular temperature regulation and [[diabetes insipidus]] are also possible symptoms of hypothalamic dysfunction.<ref name=":3">{{Cite web|url=http://www.chop.edu/news/rohhad-rapid-onset-obesity-breathing-and-behavioral-issues-indicate-very-sick-patient|title=ROHHAD: Rapid-onset Obesity, Breathing and Behavioral Issues Indicate a Very Sick Patient|last=Philadelphia|first=The Children's Hospital of|date=2016-08-24|website=www.chop.edu|access-date=2018-06-03}}</ref>
===Autonomic Dysregulation===
The [[autonomic nervous system]] controls involuntary bodily functions. In ROHHAD, autonomic dysregulation may present as:
* [[Bradycardia]] or [[tachycardia]]
* [[Blood pressure]] instability
* [[Gastrointestinal dysmotility]]
* [[Pupillary abnormalities]]


ROHHAD patients develop these symptoms at varying ages and in varying numbers, but all patients will develop some symptoms of hypothalamic dysfunction.<ref name=":0" />
==Diagnosis==
Diagnosing ROHHAD is challenging due to its rarity and the overlap of symptoms with other conditions. A comprehensive clinical evaluation is essential, including:
* Detailed medical history and physical examination
* [[Polysomnography]] to assess sleep-related breathing disorders
* [[Magnetic resonance imaging]] (MRI) of the brain to evaluate hypothalamic abnormalities
* Genetic testing to rule out other syndromes, such as [[Congenital Central Hypoventilation Syndrome]] (CCHS)


=== Hypoventilation ===
==Etiology==
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.<ref name=":0" /> Obstructive sleep apena 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.<ref>{{Cite news|url=https://www.mayoclinic.org/diseases-conditions/obstructive-sleep-apnea/symptoms-causes/syc-20352090|title=Obstructive sleep apnea - Symptoms and causes|work=Mayo Clinic|access-date=2018-06-06}}</ref> Every patient diagnosed with ROHHAD develops [[Central hypoventilation syndrome|alveolar hypoventilation]], regardless of whether they presented with sleep apnea.<ref name=":0" /> 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.<ref>{{Cite news|url=https://www.scripps.org/articles/2743-primary-alveolar-hypoventilation|title=Primary alveolar hypoventilation|date=2008-08-28|work=Scripps Health|access-date=2018-06-06}}</ref> 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 [[Cardiac arrest|cardiopulmonary arrest]], which is why ROHHAD has the potential to be a fatal disease.<ref name=":0" /> 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).<ref name=":0" /><ref name=":3" />
The exact cause of ROHHAD remains unknown. Current research suggests a possible genetic component, although no specific genetic mutations have been consistently identified. Some studies have proposed an autoimmune mechanism, but further research is needed to confirm these hypotheses.


=== Autonomic Dysfunction ===
==Management==
Autonomic dysfunction refers to the [[autonomic nervous system]], which is responsible for regulating internal processes without conscious intervention.<ref>{{Cite news|url=https://www.britannica.com/science/autonomic-nervous-system|title=autonomic nervous system {{!}} Divisions & Functions|work=Encyclopedia Britannica|access-date=2018-06-06}}</ref> 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.<ref name=":0" /> Examples of autonomic dysfunction include [[hyperthermia]], [[hypothermia]], pupillary dysfunction, [[strabismus]], chronic constipation, and chronic diarrhea.<ref name=":4">{{Cite journal|last=Bougnères|first=Pierre|last2=Pantalone|first2=Letitia|last3=Linglart|first3=Agnès|last4=Rothenbühler|first4=Anya|last5=Le Stunff|first5=Catherine|date=October 2008|title=Endocrine Manifestations of the Rapid-Onset Obesity with Hypoventilation, Hypothalamic, Autonomic Dysregulation, and Neural Tumor Syndrome in Childhood|journal=The Journal of Clinical Endocrinology & Metabolism|volume=93|issue=10|pages=3971–3980|doi=10.1210/jc.2008-0238|pmid=18628522|issn=0021-972X}}</ref>
There is no cure for ROHHAD, and treatment focuses on managing symptoms and preventing complications. A multidisciplinary approach is often required, involving:
* [[Endocrinologists]] for hormonal imbalances
* [[Pulmonologists]] for respiratory support
* [[Neurologists]] for autonomic dysfunction
* [[Psychologists]] for behavioral and emotional support


=== Neuroendocrine tumors ===
Specific interventions may include:
Approximately 40% of ROHHAD patients will develop tumors originating in the [[neural crest]].<ref name=":5">{{Cite journal|date=2017-11-01|title=Rapid-onset obesity with hypothalamic dysregulation, hypoventilation, and autonomic dysregulation (ROHHAD syndrome): A case report and literature review|journal=Neurología (English Edition)|volume=32|issue=9|pages=616–622|doi=10.1016/j.nrleng.2016.04.003|issn=2173-5808|last1=Ibáñez-Micó|first1=S.|last2=Marcos Oltra|first2=A.M.|last3=De Murcia Lemauviel|first3=S.|last4=Ruiz Pruneda|first4=R.|last5=Martínez Ferrández|first5=C.|last6=Domingo Jiménez|first6=R.}}</ref> These tumors are typically classified as [[ganglioneuroma]] or [[ganglioneuroblastoma]]s.<ref name=":4" /> These tumors are not believed to significantly worsen or contribute to the prognosis of ROHHAD.<ref name=":6">{{Cite journal|last=Pontual|first=Loic De|last2=Trochet|first2=Delphine|last3=Caillat-Zucman|first3=Sophie|last4=Shenab|first4=Othman A Abou|last5=Bougneres|first5=Pierre|last6=Crow|first6=Yanick|last7=Cunningham|first7=Steve|last8=Esteva|first8=Blandine|last9=Heberle|first9=Lada Cindro|date=December 2008|title=Delineation of Late Onset Hypoventilation Associated with Hypothalamic Dysfunction Syndrome|journal=Pediatric Research|volume=64|issue=6|pages=689–694|doi=10.1203/PDR.0b013e318187dd0e|pmid=18670370|issn=0031-3998}}</ref> 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.<ref name=":0" /><ref>{{Cite journal|last=Kocaay|first=Pınar|last2=Şıklar|first2=Zeynep|last3=Çamtosun|first3=Emine|last4=Kendirli|first4=Tanıl|last5=Berberoğlu|first5=Merih|date=December 2014|title=ROHHAD Syndrome: Reasons for Diagnostic Difficulties in Obesity|journal=Journal of Clinical Research in Pediatric Endocrinology|volume=6|issue=4|pages=254–257|doi=10.4274/jcrpe.1432|issn=1308-5727|pmc=4293662|pmid=25541898}}</ref>
* [[Ventilatory support]] such as [[non-invasive ventilation]] or [[tracheostomy]]
* [[Hormone replacement therapy]] for endocrine abnormalities
* [[Behavioral therapy]] and [[dietary management]] for obesity


=== Behavioral issues ===
==Prognosis==
Some children diagnosed with ROHHAD may also prevent with behavioral disorders and/or intellectual disability,<ref name=":2">{{Cite web|url=https://rarediseases.info.nih.gov/diseases/10407/rohhad|title=ROHHAD {{!}} Genetic and Rare Diseases Information Center (GARD) – an NCATS Program|website=rarediseases.info.nih.gov|access-date=2018-06-03}}</ref> 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 (medical)|hypoxia]] from hypoventilation or during cardiopulmonary arrest.<ref name=":0" />
The prognosis for individuals with ROHHAD varies. Early diagnosis and comprehensive management can improve quality of life and reduce the risk of life-threatening complications. However, the disorder is chronic, and ongoing medical care is typically required.


== Etiology ==
==Research Directions==
The etiology of ROHHAD is currently unknown, and the condition is diagnosed based on a set of clinical criteria.<ref name=":5" /> It is believed that there may be a genetic component to ROHHAD, however there is no widely accepted gene linked to the disease.<ref name=":0" /> 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.<ref>{{Cite journal|last=Thaker|first=Vidhu V.|last2=Esteves|first2=Kristyn M.|last3=Towne|first3=Meghan C.|last4=Brownstein|first4=Catherine A.|last5=James|first5=Philip M.|last6=Crowley|first6=Laura|last7=Hirschhorn|first7=Joel N.|last8=Elsea|first8=Sarah H.|last9=Beggs|first9=Alan H.|date=May 2015|title=Whole exome sequencing identifies RAI1 mutation in a morbidly obese child diagnosed with ROHHAD syndrome|journal=The Journal of Clinical Endocrinology and Metabolism|volume=100|issue=5|pages=1723–1730|doi=10.1210/jc.2014-4215|issn=1945-7197|pmc=4422892|pmid=25781356}}</ref>
Ongoing research aims to better understand the pathophysiology of ROHHAD and to identify potential genetic or environmental factors contributing to the disorder. Collaborative efforts are needed to develop targeted therapies and improve outcomes for affected individuals.


It is believed that ROHHAD originates from a combination of genetic and environmental or immunological factors.<ref name=":5" /> As of yet, evidence of its etiology has not been discovered and is not well understood.<ref name=":5" />
==See Also==
* [[Congenital Central Hypoventilation Syndrome]]
* [[Prader-Willi Syndrome]]
* [[Obesity hypoventilation syndrome]]


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 [[Epigenetics|epigenetic]] etiology.<ref>{{Cite journal|last=Patwari|first=Pallavi P.|last2=Rand|first2=Casey M.|last3=Berry-Kravis|first3=Elizabeth M.|last4=Ize-Ludlow|first4=Diego|last5=Weese-Mayer|first5=Debra E.|date=2011-09-01|title=Monozygotic Twins Discordant for ROHHAD Phenotype|url=http://pediatrics.aappublications.org/content/128/3/e711|journal=Pediatrics|volume=128|issue=3|pages=e711–e715|doi=10.1542/peds.2011-0155|issn=0031-4005|pmid=21807698}}</ref>
==References==
 
<references />
== Pathophysiology ==
The pathophysiology of ROHHAD is not currently known or understood.<ref name=":5" />
 
== 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.<ref name=":1" /> 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.<ref name=":4" /> 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.<ref name=":6" />
 
As the symptoms of ROHHAD are so diverse and the condition is so rare, the disease is often misdiagnosed as [[Cushing's syndrome|Cushing's disease]] or [[Central hypoventilation syndrome|Congenital Central Hypoventilation Syndrom]]<nowiki/>e when it first presents in patients.<ref name=":4" />
 
== Prevention ==
As the cause of ROHHAD is unknown, there is no way to prevent onset of the disease.<ref name=":2" />
 
== 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.<ref name=":7" />
 
=== 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.<ref name=":0" />
 
=== 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.


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.<ref name=":0" /> Patients who present with diabetes insipidus may also be treated with desmopressin, a synthetic replacement for anti-diuretic hormone.<ref>{{Cite web|url=https://www.mayoclinic.org/diseases-conditions/diabetes-insipidus/diagnosis-treatment/drc-20351274|title=Diabetes insipidus - Diagnosis and treatment - Mayo Clinic|website=www.mayoclinic.org|access-date=2018-06-10}}</ref>
==External Links==
* [ROHHAD Association](https://www.rohhadassociation.com/)
* [National Organization for Rare Disorders (NORD) - ROHHAD](https://rarediseases.org/rare-diseases/rohhad/)


=== Hypoventilation treatment ===
Every ROHHAD patient requires some form of ventilatory support, ranging from non-invasive [[Non-invasive ventilation|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.<ref name=":5" />
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.<ref>{{Cite web|url=https://www.hopkinsmedicine.org/healthlibrary/test_procedures/neurological/bipap_135,314|title=BiPap {{!}} Johns Hopkins Medicine Health Library|website=www.hopkinsmedicine.org|access-date=2018-06-08}}</ref> This is helpful for ROHHAD patients, as hypoventilation causes the mechanism that controls breathing in oxygen to slow and sometimes stop during sleep.
A [[Tracheotomy|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.<ref>{{Cite web|url=https://www.mayoclinic.org/tests-procedures/tracheostomy/about/pac-20384673|title=Tracheostomy - Mayo Clinic|website=www.mayoclinic.org|access-date=2018-06-08}}</ref> ROHHAD patients whose hypoventilation is so severe that they require support during the day and night will often undergo tracheostomies.<ref name=":3" />
=== 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.<ref>{{Cite web|url=https://www.aapos.org/terms/conditions/100|title=Strabismus — AAPOS|website=www.aapos.org|access-date=2018-06-08}}</ref> ROHHAD patients also often experience [[bradycardia]], or low heart rate. This may require a cardiac pacemaker be placed in order to regulate heartbeat.<ref>{{Cite news|url=https://www.mayoclinic.org/diseases-conditions/bradycardia/symptoms-causes/syc-20355474|title=Bradycardia - Symptoms and causes|work=Mayo Clinic|access-date=2018-06-08}}</ref>  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.<ref name=":0" />
=== 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.<ref>{{Cite journal|last=Maguire|first=Lillias H.|last2=Thomas|first2=Alyssa R.|last3=Goldstein|first3=Allan M.|date=March 2015|title=Tumors of the neural crest: Common themes in development and cancer|journal=Developmental Dynamics|volume=244|issue=3|pages=311–322|doi=10.1002/dvdy.24226|issn=1097-0177|pmid=25382669}}</ref> It is therefore important for ROHHAD patients to have regular MRI and CT scans to screen for tumor growth.<ref name=":4" /> It is believed that these tumors do not significantly affect the prognosis for ROHHAD patients.<ref name=":6" /> 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.<ref name=":0" />
== Outcomes/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.<ref name=":1" /> The earlier symptoms are identified and patients are diagnosed, the more positive their outcomes are.<ref name=":5" />
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.<ref name=":7">{{Cite journal|last=Weese-Mayer|first=Debra E.|last2=Rand|first2=Casey M.|last3=Ize-Ludlow|first3=Diego|date=August 2013|title=Commentary: Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD): Remember Your ABCs (Airway, Breathing, Circulation)|journal=Journal of the Canadian Academy of Child and Adolescent Psychiatry|volume=22|issue=3|pages=238–239|issn=1719-8429|pmc=3749899|pmid=23970914}}</ref>
== Research ==
A group at [[Lurie Children's Hospital|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.<ref>{{Cite news|url=http://www.rohhadassociation.com/?page_id=513|title=ROHHAD Research - ROHHAD Association|work=ROHHAD Association|access-date=2018-06-19}}</ref>
As of June 2018, there are 3 clinical trials currently recruiting patients with ROHHAD being performed respectively at Lurie Children's Hospital, [https://www.hopkinsmedicine.org/kimmel_cancer_center/index.html Sidney Kimmel Cancer Center], and [[Boston Children's Hospital]].<ref>{{Cite news|url=https://www.clinicaltrials.gov/ct2/results?term=ROHHAD&Search=Search|title=Search of: ROHHAD - List Results - ClinicalTrials.gov|access-date=2018-06-19}}</ref>
== Epidemiology ==
There have been at least 100 documented cases of ROHHAD worldwide.<ref name=":0" />
== History ==
ROHHAD was first described in 1965, and this was believed to be the first reported instance of hypoventilation presenting alongside hypothalamic dysfunction.<ref name=":8">{{Cite journal|last=FISHMAN|first=L. S.|date=1965-08-01|title=Primary Alveolar Hypoventilation Syndrome (Ondine's Curse)|url=https://jamanetwork.com/journals/jamapediatrics/article-abstract/501457|journal=American Journal of Diseases of Children|volume=110|issue=2|pages=155–61|doi=10.1001/archpedi.1965.02090030165011|pmid=14320765|issn=0002-922X}}</ref>
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.<ref>{{Cite journal|last=Ize-Ludlow|first=Diego|last2=Gray|first2=Juliette A.|last3=Sperling|first3=Mark A.|last4=Berry-Kravis|first4=Elizabeth M.|last5=Milunsky|first5=Jeff M.|last6=Farooqi|first6=I. Sadaf|last7=Rand|first7=Casey M.|last8=Weese-Mayer|first8=Debra E.|date=July 2007|title=Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation presenting in childhood|journal=Pediatrics|volume=120|issue=1|pages=e179–188|doi=10.1542/peds.2006-3324|issn=1098-4275|pmid=17606542}}</ref>
== Organizations ==
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.<ref>{{Cite news|url=http://www.rohhadassociation.com/?page_id=149|title=About Us - ROHHAD Association|work=ROHHAD Association|access-date=2018-06-19}}</ref> 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.
== See also ==
* [[Central hypoventilation syndrome]]
* [[Obesity hypoventilation syndrome]]
* [[Hypoventilation]]
* [[Hypothalamus]]
* [[Rare disease]]
== References ==
<references />
{{adapted}}
[[Category:Idiopathic diseases]]
[[Category:Rare diseases]]
[[Category:Rare diseases]]
[[Category:Endocrine diseases]]
[[Category:Pediatric endocrinology]]
[[Category:Respiratory diseases]]
[[Category:Neurological disorders]]

Revision as of 02:12, 2 January 2025

ROHHAD
Synonyms N/A
Pronounce N/A
Specialty N/A
Symptoms Rapid-onset obesity, hypoventilation, hypothalamic dysfunction, autonomic dysregulation
Complications N/A
Onset Childhood
Duration Chronic
Types N/A
Causes Unknown
Risks Genetic predisposition
Diagnosis Clinical evaluation, genetic testing
Differential diagnosis N/A
Prevention N/A
Treatment Symptomatic management
Medication N/A
Prognosis Variable
Frequency Rare
Deaths N/A


ROHHAD is an acronym for Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation. It is a rare and complex pediatric disorder characterized by a constellation of symptoms that typically begin in early childhood. The etiology of ROHHAD is currently unknown, and it presents significant challenges in diagnosis and management.

Clinical Features

ROHHAD syndrome is marked by a distinct set of clinical features:

Rapid-onset Obesity

Children with ROHHAD experience a sudden and dramatic increase in weight, often over a period of 6 to 12 months. This rapid weight gain is not associated with changes in diet or physical activity levels and is one of the earliest signs of the disorder.

Hypothalamic Dysfunction

The hypothalamus is a critical brain region involved in regulating various bodily functions, including hunger, thirst, sleep, and temperature. In ROHHAD, hypothalamic dysfunction can lead to:

Hypoventilation

Hypoventilation refers to inadequate ventilation leading to elevated levels of carbon dioxide in the blood. In ROHHAD, this can manifest as:

  • Sleep apnea
  • Daytime hypoventilation
  • Respiratory failure

Autonomic Dysregulation

The autonomic nervous system controls involuntary bodily functions. In ROHHAD, autonomic dysregulation may present as:

Diagnosis

Diagnosing ROHHAD is challenging due to its rarity and the overlap of symptoms with other conditions. A comprehensive clinical evaluation is essential, including:

Etiology

The exact cause of ROHHAD remains unknown. Current research suggests a possible genetic component, although no specific genetic mutations have been consistently identified. Some studies have proposed an autoimmune mechanism, but further research is needed to confirm these hypotheses.

Management

There is no cure for ROHHAD, and treatment focuses on managing symptoms and preventing complications. A multidisciplinary approach is often required, involving:

Specific interventions may include:

Prognosis

The prognosis for individuals with ROHHAD varies. Early diagnosis and comprehensive management can improve quality of life and reduce the risk of life-threatening complications. However, the disorder is chronic, and ongoing medical care is typically required.

Research Directions

Ongoing research aims to better understand the pathophysiology of ROHHAD and to identify potential genetic or environmental factors contributing to the disorder. Collaborative efforts are needed to develop targeted therapies and improve outcomes for affected individuals.

See Also

References

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External Links

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