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Table 2 Clinical Comparison Between ROHHAD & Prader-Willi Syndrome Phenotypes

From: ROHHAD and Prader-Willi syndrome (PWS): clinical and genetic comparison

Feature Present in ROHHAD Present in PWS
Main Features of ROHHAD
 Normal neonatal development Yes No
Rapid-onset obesity Yes
Over 3–12 months.
Yes
Less steep trajectory.
Hypoventilation Yes
Universal and severe - All ROHHAD patients eventually require, at a minimum, artificial ventilation during sleep, with as many as half requiring ventilation 24 h per day. If adequate ventilatory support is not provided, many ROHHAD patients suffer a cardiorespiratory arrest [1, 4, 5, 20,21,22,23,24,25].
Sometimes
Not universal, though at times severe, with some instances of cardiorespiratory arrest reported [33, 34].
Hypothalamic dysfunction Yes Yes
  Inability to maintain normal water balance Yes No
  Failed growth hormone stimulation test or growth hormone insufficiency Sometimes
Only rarely manifests as slowed growth rate or short stature.
Yes
Growth hormone deficiency results in the characteristic short stature of PWS patients.
  Hyperprolactinemia Yes No
  Hypothyroidism Sometimes Sometimes
  Adrenal insufficiency Sometimes Sometimes
  Early or late puberty Sometimes Sometimes
Autonomic dysregulation Yes Yes
  Bradycardia Sometimes
Typically temperature-related.
No
  Gastrointestinal dysmotility Yes Sometimes
  Neural crest tumors (typically benign) Yes
40–50% of cases
No
  Ophthalmologic manifestations Yes Yes
  Pain perception altered (elevated threshold) Yes Yes
  Sweating (profuse) Yes No
  Thermal dysregulation (reduced core temperature) Yes
Manifests most typically as hypothermia, despite a preference for light weight clothing regardless of ambient temperature.
Yes
PWS patients are seen to have unstable temperatures, becoming hyper- or hypothermic easily in hot or cold environments and responding poorly to fevers, with very high temperatures occurring when ill, and sometimes without explanation. PWS patients also have a higher threshold for thermal sensing.
  Vasomotor tone (ice cold hands and feet) Yes No
Main Features of PWS
 Decreased fetal movement No Yes
 Neonatal hypotonia No Yes
 Neonatal feeding problems No Yes
 Neonatal lethargy No Yes
 Delayed motor skills No Yes
 Hypogonadism No Yes
Early or delayed puberty, stalled puberty Sometimes Yes
 Intellectual disability or developmental delay preceding obesity No
Most ROHHAD patients have normal IQ. However, there are rare cases of developmental delay and one case of mild intellectual disability [1]. It has been hypothesized however, that these issues occur only after inadequate oxygenation due to undiagnosed or improperly managed hypoventilation [8].
Yes
Children with PWS are delayed in reaching cognitive, motor, and language milestones. Older PWS patients have IQ scores ranging from the high range for intellectual disability to the low range of normal, with most PWS patients showing mild intellectual disability. In addition, most PWS patients have learning disabilities.
 Autism spectrum disorder No Yes
Diagnosed in up to a quarter of PWS patients.
Maladaptive behavior (impulsive, compulsive, manipulative) Sometimes
It has been our experience that most ROHHAD patients, as long as their hypoventilation has been adequately managed, have no disordered behavior. However, there are case reports of severe behavioral issues including anxiety, depression, rage, aggressiveness, psychosis, and obsessive compulsive disorder [1, 23, 25, 35,36,37]. It has been hypothesized however, that these issues occur only after inadequate oxygenation due to undiagnosed or improperly managed hypoventilation, since these symptoms are not seen in patients who were diagnosed early and managed conservatively, and have not experienced a frank cardiopulmonary arrest [8]
Yes
There is a characteristic disordered behavioral pattern among PWS patients that includes temper tantrums, stubbornness, rigidity, compulsiveness, and controlling or manipulative behaviors. Psychosis is seen in a small number of PWS patients (5–10%).
Eye abnormalities (strabismus) Yes Yes
Growth hormone deficiency Sometimes Yes
 Short stature No Yes
Excessive weight gain independent of oral intake Yes Yes
 Hyperphagia-induced obesity No
Initial weight gain is accompanied by only mild hyperphagia. But while a restricted diet can usually slow weight gain in ROHHAD, weight gain cannot be halted completely, and weight loss is exceedingly difficult to achieve.
Yes
Weight gain initially occurs without noticeable hyperphagia, but then even greater weight gain occurs with extreme hyperphagia later in childhood.
 Excessive daytime sleepiness No Yes
 Sleep abnormalities No Yes
Central apnea Rarely
(hypoventilation is more characteristic)
Yes
Obstructive sleep apnea Sometimes
Initially, but resolves with intervention.
Yes
 Reduced activity No Yes
 Higher threshold for thermal sensing No Yes
 Decreased saliva flow No Yes
 High vomiting threshold No Yes
Scoliosis Sometimes
In ROHHAD, scoliosis is generally associated with thoracic neural crest tumors, whereas these tumors do not occur in PWS. However there is one reported case of a ROHHAD patient with scoliosis without a neural crest tumor [38].
Yes
Scoliosis is more common in PWS than in ROHHAD, and likely due to the PWS-related hypotonia.
Additional Features of PWS
 Small hands/feet No Sometimes
 Dysmorphic facial features No Sometimes
Central hypothyroidism Sometimes Sometimes
Central adrenal insufficiency Sometimes Sometimes
 Hip dysplasia No Sometimes
 Osteopenia and osteoporosis No Sometimes
 Skin picking No Sometimes
 Temperature instability No Sometimes
 Hypopigmentation No Sometimes
Seizures Sometimes
In ROHHAD, seizures are typically linked to episodes of hypoxemia.
Sometimes
A subset of PWS patients suffers from a generalized seizure disorder of ranging severity (from febrile seizures to generalized epilepsy) [39].
  1. ‘Yes’ indicates that the symptom is a typical finding among patients
  2. ‘No’ indicates that the symptom is not typically seen among patients
  3. ‘Sometimes’ indicates that the symptom does recur among patients, but not so often as to be called ‘typical’
  4. Bolded rows represent apparently overlapping symptoms
  5. ROHHAD data are primarily taken from references [1, 5], and from our own clinical experience, with additional references as listed in the table
  6. PWS data are primarily taken from references [9,10,11], and from our own clinical experience, with additional references as listed in this Table