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Table of Contents
CLINICAL ARTICLE
Year : 2021  |  Volume : 22  |  Issue : 1  |  Page : 10-15

Case presentation on ROHHAD syndrome


Associate Professor, Narayana Hrudayalaya College of Nursing, Bengaluru, Karnataka, India

Date of Submission14-Oct-2019
Date of Decision28-Sep-2020
Date of Acceptance26-Mar-2021
Date of Web Publication07-Jul-2021

Correspondence Address:
Mrs. Jeyasutha Chokkian
Narayana Hrudayalaya College of Nursing, Bengaluru, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijcn.ijcn_30_21

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  Abstract 


Rapid-onset obesity with hypothalamic dysregulation, hypoventilation and autonomic dysregulation (ROHHAD) is a rare, potentially life-threatening disorder of respiratory control and autonomic nervous system with endocrine system abnormalities. Aetiology is unknown, but some hypotheses suggest a genetic predisposition or an autoimmune reaction for the occurrence of the disorder. Patients with ROHHAD have impairment of respiratory centre in the brain stem which may cause respiratory depression. Children may experience the following symptoms such as rapid-onset obesity, hyperphagia and endocrine abnormalities. Along with these symptoms, children may experience central alveolar hypoventilation, intestinal abnormalities, body temperature irregularities, difficulty with mobility and eye abnormalities. Children should undergo many investigations to rule out the ROHHAD syndrome such as X-ray, magnetic resonance imaging, electroencephalography and gene analysis. There is no specific treatment for ROHHAD syndrome. Management of a child with ROHHAD syndrome is a multidisciplinary team approach based on the child's symptoms such as diet, exercise, hormone replacement, behavioural therapy, support with artificial ventilation and medication. Nurses have a vital role in supporting the children with ROHHAD syndrome and their families.

Keywords: Children, genetic disorder, rare disease, rapid-onset obesity with hypothalamic dysregulation, hypoventilation and autonomic dysregulation


How to cite this article:
Chokkian J. Case presentation on ROHHAD syndrome. Indian J Cont Nsg Edn 2021;22:10-5

How to cite this URL:
Chokkian J. Case presentation on ROHHAD syndrome. Indian J Cont Nsg Edn [serial online] 2021 [cited 2021 Sep 25];22:10-5. Available from: https://www.ijcne.org/text.asp?2021/22/1/10/320819




  Introduction Top


Rapid-onset obesity with hypothalamic dysregulation hypoventilation and autonomic dysregulation (ROHHAD) is a rare potentially life-threatening genetic disorder in children. ROHHAD affects the respiratory system, autonomic nervous system and endocrine system. Children with ROHHAD appear to have normal growth and development and general health prior to onset of symptoms. In 1965, Fishman was the first to describe the constellation of symptoms that he termed as the late onset of central hypoventilation syndrome with hypothalamic dysfunction.[1],[2] In 2007, Ize-Ludlow et al. renamed the disease using the acronym ROHHAD.[3] The disease is associated with a predisposition to tumours of neural crest origin, which is why the abbreviation ROHHAD-neural tumour syndrome is also found in literature.[4]

ACRONYM

ROHHAD & ROHHAD NET

  • R - Rapid Onset
  • O - Obesity
  • H - Hypoventilation
  • H - Hypothalamic dysregulation
  • AD - Autonomic dysregulation
  • >NET - Neural tumor syndrome


ROHHAD syndrome is a rare genetic disorder of respiratory control and autonomic nervous system with endocrine system abnormalities. The onset of disease is generally between 2 and 4 years of age[3] (median– 3 years), but the symptoms can manifest anytime during the 1st 10 years of life.[3] Both boys and girls are affected.[5] According to the Genetic Rare Disease Information Centre, there are 100 cases reported worldwide till date. The prevalence is <1/1 000 000.[5] Aetiology of ROHHAD is unknown. It is hypothesised that heterozygous mutations of the PHOX2B gene such as 20-alanine tract expansion (+5 to +13 alanines) and occasional frameshift or missense mutations cause central hypoventilation in congenital central hypoventilation syndrome and may be the same in ROHHAD;[6] however, it is now established that there is no PHOX2B mutation associated with ROHHAD syndrome.[4] It has been speculated that autoimmune processes could be an underlying factor for the disease, but it has not yet been possible to associate ROHHAD with the presence of specific autoantibodies. Reports of ROHHAD in siblings suggest a possible genetic component responsible for the disease.[7]


  Pathophysiology Top


There is a diversity of neurons that are present in the hypothalamic and peripheral neuroendocrine system and the respective populations differ with regard to their development, gene expression and antigenic characteristics. There are two neurosecretory systems involved in hypothalamic hormone secretion, namely magnocellular and parvocellular systems [Figure 1]. The magnocellular system consists of specialised large neurons, the hypothalamo-neurohypophysial tract and the neurohypophysis. The main products are antidiuretic hormone and oxytocin. The parvocellular system is composed of smaller neurons that produce hypophysiotrophic hormone. The clinical manifestations in ROHHAD patients resemble symptoms due to deficiencies of magnocellular and parvocellular systems [Figure 1].[7] The respiratory depression is due to the impairment of the respiratory system in the brain stem.[4]
Figure 1: Magnocellular and parvocellular pathways in the brain

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Activities of daily living such as exercise, rest and sleep moderate the autonomic function of breathing. The autonomic nervous system also regulates many involuntary body functions such as heart rate, blood pressure, temperature regulation, bowel and bladder control. The endocrine system is regulated by hypothalamus and the hormones produced influence an individual's growth, energy, water balance, sexual maturation, fertility and response to stress. The combination of hypothalamic, autonomic nervous system and endocrine systems dysfunction produces the various manifestations seen in ROHHAD disease[8] [Figure 2].
Figure 2: Pathophysiology in rapid-onset obesity with hypothalamic dysregulation, hypoventilation and autonomic dysregulation syndrome

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  Clinical Manifestations Top


Children with ROHHAD are apparently normal before the onset of symptoms. The manifestations usually start around the age of 3 years and the first and most common manifestation is the rapid and dramatic increase in weight (about 10 kg) in 6 months to 12 months.[4],[9] Children manifest increased hunger (hyperphagia), especially during the initial months of weight gain. Other hypothalamic endocrine dysfunctions usually are seen within <1 year of the onset of weight gain and include.[8]

  • Inability to maintain normal water balance in the body (abnormally high or low sodium levels and diabetes insipidus) leading to diminished or excess thirst and polyuria
  • high prolactin levels
  • central hypothyroidism
  • growth hormone deficiency
  • Early or late puberty.


Hypoventilation is the key symptoms which is helpful in confirming the diagnosis. Obstructive sleep apnoea is a common manifestation in many children with ROHHAD.[10] Children with sleep apnoea may have complaints of snoring, teeth grinding, etc., Irregular breathing pattern during wake hours also is common. Cardiorespiratory arrest due to hypoventilation/respiratory insufficiency is a common cause of death if undiagnosed.[8] Cyanotic episodes are also a common feature in children with ROHHAD.[4]

The autonomic dysregulation can cause: [7]

  • Decreased heart rate or increased heart rate
  • Diarrhoea or constipation
  • Imbalanced coordination of body movement
  • Dysautonomia
  • Early or delayed puberty
  • Sweating
  • Decreased or increased body temperature
  • Eye abnormalities – strabismus astigmatism.


Altered perception of pain was also seen in many children.[4]

Seizures approximately 40% of children develop tumours in neural crest cells such as ganglioneuromas and ganglioneuroblastomas.[4]

Children with ROHHAD were also found to have developmental delay behavioural disorders such as aggressiveness and hyperactivity and psychiatric problems such as anxiety, depression, hallucinations and psychosis.[6],[9]


  Diagnostic Evaluation Top


History collection – History of weight gain (10–15 kg in 6–12 months) and history of breathing difficulty, or snoring suggestive of sleep apnoea, history polydipsia, polyphagia, aggressiveness and mood disorders were taken.

Blood sample – High levels of prolactin, low level of TSH, low to very low levels of growth hormones, low or high levels of sodium, abnormal levels of vasopressin will be observed.

Chest X-ray – It was used to identify the pulmonary abnormalities.

Polysomnography – It was used to identify obstructive sleep apnoea and central hypoventilation.

  • Echocardiogram – To identify the cardiac abnormalities
  • Endocrine investigation – To identify pituitary function and water balance regulation (hyponatraemia or hypernatraemia and low thyroid level)
  • Magnetic resonance imaging (MRI) – To identify the abnormalities in the brain such as tumour in the neural crest cells
  • Electroencephalography (EEG) – To identify the electrical function of the brain
  • Gene analysis – Absence of PHOX2B gene mutations.[4]



  Management of Child with Rapid-Onset Obesity with Hypothalamic Dysregulation, Hypoventilation and Autonomic Dysregulation Syndrome Top


There is no specific management to treat ROHHAD syndrome. Management of a child with ROHHAD syndrome is a multidisciplinary team approach and management based on the child's manifestations [Figure 3].
Figure 3: Multidisciplinary approach in rapid-onset obesity with hypothalamic dysregulation, hypoventilation and autonomic dysregulation [11]

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  • Obesity management
  • Exercise – Vigorous exercise is dangerous as their breathing will increase with exertion which causes hypoxia. Children with ROHHAD syndrome should exercise with moderate intensity and their oxygen levels to be monitored throughout the activity[10]
  • Diet management with consultation of nutrition therapist based on individual needs of children and strict adherence to diet control to reduce weight gain.[4]
  • Hypothalamic dysfunction


    • Hormone replacement for diabetes insipidus
    • Administration of growth hormone
    • Strict fluid intake.


  • Behavioural problem


    • Behavioural therapy.


  • Eye problem treated with glasses, eye muscle exercises or even surgery
  • Gastrointestinal problems are treated with laxatives
  • Seizures.


    • Anti-epileptic medication such as eptoin and phenytoin.


  • Immunosupportive drugs.


High-dose cyclophosphamide is found to be useful in improvement in symptoms in children with ROHHAD.[12]

(Doses may vary according to the symptoms of the children).

  • Severe bradycardia


    • Cardiac pacemaker.


  • Central hypoventilation


    • Support with artificial ventilation. Noninvasive ventilation is very useful[10]
    • Support of sleep medicine (if needed)
    • Tracheostomy may be needed.[4]


  • Tumour of neuro crest cells to be removed by surgery.


Prognosis

The prognosis of ROHHAD syndrome is based on earlier symptom identification. Children who are diagnosed early and appropriately managed have a good quality of life. Approximately 50% to 60% of patients will die due to cardiopulmonary arrest.


  Case Report Top


Child X was normal up to 3 years of age. At 3 years and 1 month of age, child X presented with the symptoms of a gradual increase of body weight around 8 kg within 6 months. A day prior to admission, the child suddenly developed the symptoms of breathing difficulty during sleeping. Hypoventilation during sleeping was identified in the hospital and the child underwent tracheostomy and was started on bilevel positive airway pressure (BiPAP) support at the age of 3 years 1 month. During the assessment, the child had strabismus, decreased range of motion, imbalanced co-ordination and the presence of crackle sound on auscultation of the lung. Blood investigations, MRI, chest X-ray and polysomnography were performed. The serum thyroxin value was found to be 1.36 mu/IU (normal – 4.6–12 ug/dl) and TSH level was 2.215 mu/IU (Normal-0.5–5.0 mIU/L). The MRI reported multiple hyperintense foci on T2 images suppressed on FLAIR with peripheral hyperintensity in the subcortical and periventricular white matter on the parietal, frontal, temporal and occipital lobes bilaterally. The chest X-ray showed an ill-defined mass lesion in the presacral region. The polysomnography showed evidence of poor sleep quality and inadequate thorax and abdomen respiratory efforts with an oxygen saturation of 80%. The child was sleeping supine position most of the time. A diagnosis of ROHHAD syndrome was confirmed for the child.

At the present admission, the child came with BIPAP mode (O2 8 l/min) during sleeping for the last 1 year 5 months. Child X was admitted presently with complaints of vomiting and loose stool for 5 times in the past 1 h. The child manifested with severe dehydration. In a hospital, the child developed with one episode of seizure. The child's sodium level was 130 mmol/l; calcium level was 8.8 mg/dl which indicated electrolyte imbalance. The EEG done reported a mild degree of diffuse nonspecific disturbances of electrical function and no epileptic abnormalities. The MRI repeated on this admission showed multiple hyperintense foci on T2 images suppressed on FLAIR with peripheral hyperintensity in the subcortical and periventricular white matter on the parietal, frontal, temporal and occipital lobes bilaterally which have significantly increased in number and extension compared to previous MRI study and internal increase signal abnormalities in some areas of the brain. The polysomnography showed evidence of moderate sleep quality and there were normal thorax and abdominal efforts. The oxygen saturation was 96% with BIBAP mode support (O2 8 l/min). The child received tablet eptoin 25 mg twice a day for 5 days.


  Nursing Management Top


Nursing management of child X with ROHHAD is presented below using the nursing process approach.

1.Nursing Diagnosis

Impaired breathing pattern (dyspnoea) is related to tracheobronchial obstruction as evidenced by hypoventilation during sleep.

Expected outcome

The child will maintain a normal breathing pattern with the support of artificial ventilation.

Nursing intervention

  • Provide respiratory support with the help of artificial ventilation (BiPAP)
  • Maintain the alarm for sleep apnoea which helps to monitor the hypoventilation
  • Administer oxygen 8 l via BIPAP mode
  • Provide semi–Fowler's position
  • Teach the parents regarding cardiac pulmonary resuscitation (in case of emergency apnoeas and respiratory arrest)
  • Enhance parent's monitoring abilities and teach on manifestations of respiratory insufficiency.


Evaluation

The child maintained an effective breathing pattern with BIPAP mode support (O2 8 l/min).

2. Nursing Diagnosis

Impaired gas exchange pattern is related to more tracheobronchial secretions as evidenced by the presence of crackle sound during auscultation.

Expected outcome

The child will maintain an effective gas exchange pattern.

Nursing intervention

  • Provide chest physiotherapy with postural drainage
  • Perform suctioning every second hourly
  • Teach deep breathing exercise
  • Administer antibiotics as prescribed for respiratory infection.


Evaluation

The child maintained an effective gas exchange pattern as evidenced by continuous oxygen saturation up to 96% with BIBAP mode support (O2 8 l/min).

3. Nursing Diagnosis

Imbalanced nutrition more than body requirement is related to excessive intake of food as evidenced by a sudden increase of body weight (Increase of 8 kg Body weight within 6 months).

Expected outcome

The child will maintain normal nutritional status.

Nursing intervention

  • Encourage the child to perform a moderate amount of exercise through play ensuring that the exercise does not cause breathing difficulty
  • Provide more time for the child to play
  • Diet management – Avoid more calorie rich foods, provide more fruits and vegetables. Refer to a dietitian for calorie restriction
  • Provide small and frequent foods.


Evaluation

The child maintained normal nutritional status as evidenced by maintaining ideal body weight of 14 kg and reduced weight gain.

4. Nursing Diagnosis

Activity intolerance is related to imbalanced coordination as evidenced by decreased range of motion.

Expected outcome

The child will maintain normal activity within the limitation of ventilation issues.

Nursing intervention

  • Teach parents about active and passive exercises
  • Assist the child for activity of daily living
  • Allow the child to perform a small physical activity such as playing indoor games.


Evaluation

The child maintained normal activity as evidenced by doing activities of daily living.

5. Nursing Diagnosis

Fluid volume deficit related to vomiting and diarrhoea as evidenced by dry mucous membrane.

Expected outcome

The child will maintain normal fluid volume.

Nursing intervention

  • Encourage the child to drink the prescribed level of fluid
  • Administer IV fluids – 20 ml Ringer lactate/h to treat severe dehydration on the first day
  • Administer anti-emetics
  • Administer sodium supplements.


Evaluation

The child maintained normal fluid volume as evidenced by the absence of dry mucous membrane and reversal of dehydration.

6. Nursing Diagnosis

Impaired bowel movement is related to abnormalities of autonomic regulation as evidenced by diarrhoea or constipation.

Expected outcome

The child will have normal bowel movements.

Nursing intervention

  • Administer high-fibre diet to prevent constipation
  • Monitor for loose stools and provided fluids to continuously hydrate the child
  • In case of severe dehydration, IV Fluids may have to be initiated.


Evaluation

The child's diarrhoea settled within 2 days.

7. Nursing Diagnosis

Potential impairment in thermoregulation is related to abnormalities of autonomic regulation as evidenced by hypothermia or hyperthermia.

Expected outcome

The child will have normal body temperature.

Nursing intervention

  • Maintain normal room temperature (room temperature should not be low or high)
  • Teach parents to monitor body temperature regularly
  • Maintain adequate ventilation to prevent hypo- and hyperthermia
  • Teach about cold applications and administering paracetamol to treat hyperthermia
  • Cover the child with a blanket to prevent hypothermia when necessary.


Evaluation

The child maintained normal body temperature as evidenced by a body temperature of 98.6°F.


  Conclusion Top


Child X continued to be on tracheostomy with BIPAP mode (O2 8 l/min). ROHHAD is a rare disease and is often missed in the initial stages. If treated and supported adequately by continuous monitoring of ventilator needs and addressing the prognosis, the quality of life is better for these children. When the diagnosis is delayed and the condition is not adequately treated, they are more likely to have significant behaviour problems and increased risk for sudden death. Nurses play a vital role in assessing the hospitalised child at risk and help their families to cope with this rare disease.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Fishman LS, Samson JH, Sperling DR. Primary alveolar hypoventilation syndrome (Ondine's Curse): Association with manifestations of hypothalmic disease. Am J Dis Child 1965;110:155-61.  Back to cited text no. 1
    
2.
Katz ES, McGrath S, Marcus CL. Late-onset central hypoventilation with hypothalamic dysfunction: A distinct clinical syndrome. Pediatr Pulmonol 2000;29:62-8.  Back to cited text no. 2
    
3.
Ize-Ludlow D, Gray JA, Sperling MA, Berry-Kravis EM, Milunsky JM, Farooqi IS, et al. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation presenting in childhood. Pediatrics 2007;120:e179-88.  Back to cited text no. 3
    
4.
Harvengt J, Gernay C, Mastouri M, Farhat N, Lebrethon MC, Seghaye MC, et al. ROHHAD (NET) syndrome: Systematic review of the clinical timeline and recommendations for diagnosis and prognosis. J Clin Endocrinol Metab 2020;105:2119-31.  Back to cited text no. 4
    
5.
Genetic and Rare Diseases Information Center. ROHHAD Syndrome; 2018. Available from: https://rarediseases.info.nih.gov/diseases/10407/rohhad. [Last accessed on 2021 Apr 13].  Back to cited text no. 5
    
6.
Ize-Ludlow D, Vitez SF, Casey M. Rand CM, Weese-Mayer DE. Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation; 2018. Available from: https://rarediseases.org/rare-diseases/rapid-onset-obesity-with-hypothalamic-dysfunction-hypoventilation-and-autonomic-dysregulation/.-[Last accessed on 2021 Apr 13].  Back to cited text no. 6
    
7.
ROHHAD Syndrome; 2018. Available from: https://www.symptoma.com/en/info/rohhad-syndrome#info. [Last accessed on 2021 Apr 13].  Back to cited text no. 7
    
8.
Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation; 2018. Available from: https://rarediseases.org/rare-diseases/rapid-onset-obesity-with-hypothalamic-dysfunction-hypoventilation-and-autonomic-dysregulation/. [Last accessed on 2021 Apr 13].  Back to cited text no. 8
    
9.
Aljabban L, Kassab L, Bakoura NA, Alsalka MF, Maksoud I. Rapid-onset obesity, hypoventilation, hypothalamic dysfunction, autonomic dysregulation and neuroendocrine tumor syndrome with a homogenous enlargement of the pituitary gland: A case report. J Med Case Rep 2016;10:1-9.  Back to cited text no. 9
    
10.
Reppucci D, Hamilton J, Yeh EA, Katz S, Al-Saleh S, Narang I. ROHHAD syndrome and evolution of sleep disordered breathing. Orphanet J Rare Dis 2016;11:1-8.  Back to cited text no. 10
    
11.
Patwari PP, Rand CM, Berry-Kravis EM, Ize-Ludlow D, Weese-Mayer DE. Monozygotic twins discordant for ROHHAD phenotype. Pediatrics 2011;128:e711-5.  Back to cited text no. 11
    
12.
Jacobson LA, Rane S, McReynolds LJ, Steppan DA, Chen AR, Paz-Priel I. Improved Behavior and neuropsychological function in children with ROHHAD after high-dose cyclophosphamide. Pediatrics 2016;138:e20151080.  Back to cited text no. 12
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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