ROHHAD-syndrome is a very rare pathology, the essence of which is obesity on the background of hypothalamic dysfunction and hypoventilation of the central type. The trigger of the disease is gene mutations and immune disorders. Since obesity is directly related to leptin, which is responsible for human eating behavior through hypothalamic centers, the involvement of the hormone in the development of the pathology can be considered proven. You will learn about how the disease is diagnosed and treated in this article.


  1. General information.
  2. Triggers.
  3. Mechanism of development.
  4. Symptomatology.
  5. Diagnosis.
  6. Syndrome therapy.
  7. Prognosis.

General information

ROHHAD-syndrome has been known in medicine since the middle of the last century. The abbreviation of the disease, ROHHAD, translates from English as “rapidly progressing obesity with hypothalamic dysregulation, hypoventilation and autonomic dysfunction”. Today, there are about 100 patients worldwide with this syndrome. Many endocrinologists emphasize the role of neuroendocrine neoplasms in the development of the syndrome. That is why the abbreviation is now supplemented with the term NET (Neural Endocrinological Tumor).


The cause of the pathology is unknown. This is due to the rarity of the disease and the short duration of clinical observations.

Today, there are three theories of the origin of ROCKHAD-syndrome:

  1. Hereditary, based on gene mutations (PHOX2B gene). Presumably, 11 other genes are involved in the transcription information, which are responsible for the normal functioning of the nervous and endocrine system.
  2. Epigenetic, according to which monozygotic twins do not both inherit the syndrome, it may occur in only one child. It is associated with a change in the activity of certain genes without disturbing their sequence, which is formed under the influence of the environment – epigenetically.
  3. Immunological, which is diagnosed in a proportion of patients. In this case, antihypophysial and antihypothalamic antibodies are found in the cerebrospinal fluid, which can potentially damage cerebral structures and become a trigger of disorders. There is an assumption that the syndrome is associated with celiac disease and other autoimmune pathologies.

Developmental Mechanism

Mutations of the PHOX2B gene alter neural crest migration, that is, the development of the autonomic nervous system. The lost control of vital functions provokes inadequate ventilation as a compensatory reaction in response to excess carbon dioxide in blood and hypoxia. The situation is exacerbated by impaired breathing, slowed transmission of nerve impulses, which prevents the movement of the diaphragm and other components of the respiratory muscles.

Prevalent in ROCKHAD-syndrome is the symptomatology associated with the lesion of the hypothalamus, which is the key in maintaining homeostasis. It is its centers that control hunger and satiety, thermoregulation, thirst, and diuresis. Dysfunction of the hypothalamic system provokes significant metabolic shifts, which eventually leads to weight gain, water-salt metabolism disorders and endocrine imbalance. Leptin and its affiliated ghrelin become one of the tools of dysfunction development.


The clinical symptomatology of ROHHAD-syndrome first occurs from birth to 9 years of age, with the pathology most often debuting at 2-4 years of age. Until then, children’s physical and mental development is age-appropriate and no signs of pathology are observed. ROCKHAD-syndrome begins to announce itself by increasing appetite (it is the work of leptin) up to bulimia and rapid recruitment of extra pounds. Babies are obese and acquire a characteristic appearance: a moon-shaped face with puffy cheeks halfway down the face, a short thick neck, hypertelorism – increased distance between the inner corners of the eyes and pupils.

Autonomic disorders in ROCKHAD-syndrome are manifested by digestive disorders with dyspeptic disorders, strabismus, changes in the threshold of pain sensitivity. After some time, disorders of water-salt metabolism join, daily diuresis decreases, and enuresis develops.

Children with the pathology are more susceptible to respiratory infections. Respiratory disorders are considered the main symptoms of the disease. They debut in the 6th year of life with nocturnal apnea, snoring, alveolar hypoventilation.

Typical development of symptoms at night, but in severe cases the symptoms remain during the day, plus – constantly join respiratory pathologies. Parents notice cyanosis of the baby’s skin, weakness and apathy to everything that happens during the day.


Life-threatening for a child with ROHHAD-syndrome are cardiorespiratory crises, which end fatally without timely assistance: cardiac arrest is recorded.

In addition, children develop:

  • autism;
  • mental retardation;
  • behavioral disorders of the baby;
  • neurological disorders in the form of seizures;
  • ganglioneuroma formation (in more than half of all cases of pathology).

Separately, we want to emphasize that obesity syndrome is accompanied by other endocrine pathologies. The adipose tissue hormone leptin contributes here as well. For example, it has been described that ROCKHAD-syndrome is affiliated with insulin resistance, which, in turn, is directly related to leptin resistance. This provokes diabetes mellitus, hypertriglyceridemia. Such changes form fatty liver dystrophy in children, secondary hypothyroidism, dwarfism, hypogonadotropic hypogonadism.


The rarity yet versatility of the clinical manifestations of ROHHAD-syndrome makes diagnosis difficult. Young patients are examined by a pediatrician, endocrinologist, neurologist, and other narrow specialists.

Significant assistance in the correct diagnosis is provided by:

  1. Polysomnography, which allows you to determine the number and duration of nocturnal apnea attacks. The technique also records ECG, EEG, electro-oculogram, and other parameters that are important in assessing the severity of the baby’s condition.
  2. Neuroimaging, necessary to rule out tumors and congenital malformations of the central nervous system that resemble the symptomatology of ROCKHAD-syndrome. A CT or MRI scan of the brain is performed. Seizures require electroencephalography.
  3. Blood gas analysis to determine the degree of hypoventilation. An oxygen saturation of less than 95% with an increase in carbon dioxide concentration of more than 50 mm Hg while awake indicates a drop in pulmonary ventilation. Pulse oximetry is used to quickly assess the condition.
  4. Hormonal profile in ROHHAD-syndrome involves an extended study that includes tests for hormones of the pituitary-hypothalamic system, thyroid, and adrenal glands. When indicated, blood insulin concentration and glycemic profile are evaluated.

Differential diagnosis

To be confident in the exact diagnosis of the pathology, it is necessary to exclude Prader-Willi syndrome, constitutional obesity of exogenous genesis, and adiposogenital dystrophy. The neurological situation dictates the need to differentiate the syndrome with obesity, which is provoked by brain tumors, with other variants of central hypoventilation.

Therapy of the syndrome

ROCKHAD-syndrome requires comprehensive and multidisciplinary therapy involving child psychotherapists and psychologists, remedial educators and family members. To correct obesity, which is associated with eating behavior, a diet with a minimum of calories against a high content of easily digestible foods and vitamins is prescribed. Physical therapy to prevent weight gain is also necessary.

Symptomatic treatment is carried out with:

  1. Respiratory support, taking into account the severity of the syndrome and the patient’s age. It can be: face mask, nasal cannulas, noninvasive ventilation with positive pressure. In cardiorespiratory crises – classic ventilatory ventilation is used.
  2. Hormone therapy, which consists of substitution correction by thyroid and steroid hormones, and is used in concomitant endocrine pathologies.
  3. Control of water-salt metabolism is provided by limiting fluid intake and adding diuretics to the complex of measures.
  4. Additional prescription of drugs is supposed in case of digestive system disorders (enzymes, laxatives, anti-diarrheal drugs), in case of the development of neuropsychiatric disorders (anticonvulsants, antipsychotics, neurometabolic agents).


The prognosis is unfavorable, because in half of the cases cardiopulmonary failure progresses and death occurs. However, with early treatment, the prognosis improves. The disease is still poorly understood, but further in-depth study of the triggers of the disease and the mechanism of its development gives hope for the soon appearance of new methods of correction of the syndrome. For families with a sick child, genetic counseling is mandatory when planning the next pregnancy.



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