ROHHAD AND ROHHAD NET

2. • 2 years old boy case of :
• Microcephaly, mental retardation, SZ disorder,
resolved hypernatremia, sleep apnea ,morbid
obesity refered to endocrinlogy as possible
case of ROHHAD syndrome.
• Wt:>97th BMI:>97th Ht:10-25th
• On oxygen, No goitre , no purple straie.
• ACTH , cortisol: WNL. TSH:8.5 Ft4:13

3. • 9 year old girl case of ROHHADNET with :
• Rapid onset of obesity, hypoventilation on
biPAP, adipsic hypernatremia, hypothyrodisim,
S/P removal of ganglioneuroma.

4. • In 1965, Dr. Fishman was the first to describe a
constellation of symptoms which he termed
Late Onset Central Hypoventilation Syndrome
with Hypothalamic Dysfunction (LO-CHS/ HD).
• In 2007, Dr. Diego Ize-Ludlow renamed the
disease using the acronym ROHHAD.

5. • Rapid-Onset.
• Obesity.
• Hypoventilation.
• Hypothalamic.
• Autonomic Dysregulation.
• Neural tumor syndrome

6. • ROHHAD syndrome is a heterogeneous
medical condition .
• Despite increased recognition of the disorder,
its incidence is rare with fewer than 100
reported cases in the literature.
• The etiology of this syndrome is still unknown.

7. • life-threatening medical condition with death
occurring around the average chronological
age of 10.
• ROHHAD syndrome shares many clinical
similarities with congenital central alveolar
hypoventilation syndrome or Ondine’s curse.

8. • no specific genetic marker has been
implicated .
• Nevertheless, familial cases have been
reported, suggesting that it may be a
monogenic condition.
• The PHOX2B mutations implicated in CCHS are
absent in children with ROHHAD.

9. • The most common presenting symptom of
ROHHAD syndrome is hyperphagia and
obesity secondary to hypothalamic
dysfunction.
• The typical age of onset is between 2 and 4
years.

10. sudden rapid weight gain and
concomitant growth failure
(median age at onset: 3 years)
Hypothalmic and autonomic
dysregulation (median age at
onset: 3.6 years)
behavior and alveolar
hypoventilation (median age at
onset: 6.2 years).

11. • Hyperphagia
• Obesity.
• alveolar hypoventilation
• altered respiratory control or thermal or other
hypothalamic dysregulations,
• neurobehavioral disorders
• tumors of neural crest origin

12. • Growth failure GH deficiency or unresponsiveness.
• excessive secretion of ACTH, hypercortisolism
• glucocorticoid deficiency.
• hypogonadotropic hypogonadism.
• Hyperprolactinemia.
• Hypernatremia. Adipsic or Diabetes insipidus.
• hypogonadism
• precocious puberty,
• central hypothyroidism and Hyperthyrotropinemia.

13. manifestation %
Rapid-onset obesity 100 %
Failed growth hormone 60 %
stimulation test
Hyperphagia 53%
Polydipsia 53%
Hypernatremia 46-100%
Hyperprolactinemia 46%
Hypothyroidism 30%
Adrenal insufficiency 26%
Polyuria 26%
Short stature 20%
Delayed puberty 13%
Hyponatremia 13%
Low IGF-1 and IGFBP-3 13%
Precocious puberty 13%
Premature adrenarche 13%
manifestation %
Transient diabetes 13%
insipidus
Transient SIADH 13%
Hypogonadotropic 6%
hypogonadism
Irregular menses 6%
manifestation %
Alveolar hypoventilation 100%
Cardiorespiratory arrest 60%
Obstructive sleep apnea 53%

14. • rapid-onset obesity is initial manifestation of
ROHHAD (20–40 lb over 6 –12months).
• Almost simultaneously, height velocity will
decrease.
• This lead to increase in BMI.
• By 6 yr of age, all children had massive obesity.
• marked adipomastia ,chubby face and slight
buffalo neck.

16. EXOGENOUS OBESITY ROHHAD
Sleep apnea increased increased
GH unresponsiveness increased increased
TSH levels High High
height velocity increased decreased
IGF-I high low
Autonomic dysfunction absent present
Alveolar hypoventilation absent present
tumors of the sympathetic absent present
nervous system

17. • Approximately 40% of the patients may
develop neural crest tumors (ganglioneuro-blastomas,
ganglioneuromas,
• usually orginated in the posterior
mediastinum or adrenal gland.
• Neural crest tumors are composed of ganglion
cells (some of which may be immature) and
mature Schwann cells (mature stroma)
• Calcification in CT is common.

18. • Respiratory signs and symptoms may include
obstructive sleep apnea and central
hypoventilation,
• which may result in hypoxemia, hypercarbia,
cyanosis, or even cardiorespiratory arrest with
sudden death.
• median onset age 6 years
• ventilatory support is a mainstay of care

19. • The most common was thermal dysregulation,
manifest as episodes of hyperthermia or
hypothermia .
• pupillary dysfunction and Strabismus.
• Gastrointestinal dysmotility with constipation
and chronic diarrhea.

20. • mild mental retardation.
• developmental regression
• obsessive-compulsive disorder.
• personality changes, irritability, and physical
aggression.
• severe avoidance behaviors.
• Anxiety .
• sleep symptoms. insomnia, and nighttime.
• psychosis.
• seizures.

21. • irregular heart rate,
• profound bradycardia that required a cardiac
pacemaker
• Cardiomyopathy.
• heart failure.

22. • 1. rapid onset obesity after a 2 year period of
normal development both in terms of height and
weight.
• 2. hypothalamic-pituitary endocrine dysfunctions
(hypercortisolism, slow growth, low IGFI,
hyperprolactinemia, severe hypernatremia without
diabetes insipidus);
• 3. hypothalamic autonomic dysregulation (thermal
dysregulation, cold hands and feet, excessive
sweating, etc).
• 4. alveolar hypoventilation (obstructive sleep
apnea and 2 episodes of respiratory arrest post
minimal sedation).

23. Other DDx
• Prader-Willi syndrome.
• Bardet-Biedl syndrome.
• leptin receptor deficiency.
• Cushing’s syndrome.
• GH deficiency

24. • Currently there are no definitive tests or
treatments for ROHHAD.
• serial pulmonary studies at 3- to 6-month
intervals.
• screening for tumors of neural crest origin
every 12 to 18 months.
• multi-disciplinary approach is needed in any
potential case of ROHHADNET syndrome.