ROHHAD Syndrome

Rapid-onset Obesity with

Hypothalamic Dysfunction,

Hypoventilation and Autonomic

Dysregulation (ROHHAD)

Syndrome

Hari Krishnan Nair,

Visiting Medical Student,

Department of Neurology,

Boston Children’s Hospital.

A disorder of autonomic nervous system

regulation with endocrine abnormalities.

Epidemiology and Etiopathogenesis

Epidemiology

A rare condition

Approximately 100 cases reported in the

literature and clinically to date

Predominantly in patients of Caucasian

and Arabic descent

◦ One case each of Japanese, Indian and

Malaysian origin

Etiology and Pathogenesis

No specific cause has been found to date

PHOX2B mutations, which causes a

related disorder Congenital Central

Hypoventilation Syndrome, are absent in

ROHHAD

Clinical Presentation

Clinical Presentation

Children are apparently healthy until 1.5

years of age

Subsequently rapid-onset weight gain

(often 30 pounds in 6-12 months)

◦ Invariably the first symptom to appear

Hyperphagia

Hypersomnolence

Respiratory manifestations

(Median age: 6.2 years)

Alveolar hypoventilation

◦ Very shallow breathing during sleep

Cardiorespiratory arrest

Obstructive sleep apnea

Autonomic dysregulation

(Median age: 3.6 years)

Altered pupillary response to light

Strabismus

Altered GI motility

◦ Chronic constipation or diarrhea

Thermal dysregulation

◦ Hyperthermia or hypothermia

Altered pain perception

Autonomic dysregulation

Bradycardia

Altered sweating

Adipsic Hypernatremia

Hyperprolactinemia

Diabetes insipidus

Cardiac abnormalities

Arrhythmias

Blood pressure dysregulation

Right ventricular hypertrophy secondary

to cor pulmonale

Anatomic malformations of ANS

33-39%

Tumors of neural crest origin

◦ Ganglioneuromas

◦ Ganglioneuroblastomas

As late as 7-16 years

after the onset

of obesity

Neurobehavioral disorders

Behavioral, mood, and developmental

disorders

Seizures – may be related to episodes of

hypoxemia due to inadequate ventilator

support

Ataxia

Diagnostic Modalities

Clinical Testing

Overnight polysomnography

◦ For signs of obstructive sleep apnea and

central hypoventilation

Imaging of chest and abdomen

◦ To screen for evidence of neural crest tumors

Cardiac evaluation

Endocrine evaluation

◦ Water balance regulation

◦ Pituitary function

Sequential comprehensive

evaluation

Annual physiologic assessment during

spontaneous breathing awake and during

sleep

72-hour Holter recording annually to

evaluate for bradycardia

Echocardiogram annually

Neurocognitive testing annually

Management

Treatment

No specific treatment

Based on the clinical features and their

relative severity

Multidisciplinary care at a tertiary center

Obesity

Emphasis to avoid further weight gain

◦ In consultation with a nutritionist and

endocrinologist

◦ Recommend only modest exertion, with end

tidal carbon dioxide and pulse oximetry

(as patients do not increase their breathing

adequately during physical exertion)

Hypothalamic dysfunction

Hormone replacement

◦ Growth hormone administration, and

dopamine agonists to normalize prolactin

levels have not been shown to modify the

clinical course

Strict fluid intake regimen

Breathing deficit

Artificial ventilation

◦ Intially – during sleep only

◦ Later – continuous support

Most children – Mask ventilation and

BiPAP at night

Some – 24-hour mechanical ventilation

with tracheostomy

Autonomic dysregulation

Permanent pacemakers for bradycardia

Careful regulation of ambient

temperature

Neural crest tumors – surgical removal

◦ Has not interrupted the unfolding of the

ROHHAD phenotype nor induced recovery

from the ROHHAD phenotype

ROHHAD FIGHT Inc.

www.rohhadfight.org

Thank you