Table 2.

Clinical Comparison Between ROHHAD & Prader-Willi Syndrome Phenotypes

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, 20–25].	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, 35–37]. 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].

‘Yes’ indicates that the symptom is a typical finding among patients

‘No’ indicates that the symptom is not typically seen among patients

‘Sometimes’ indicates that the symptom does recur among patients, but not so often as to be called ‘typical’

Bolded rows represent apparently overlapping symptoms

ROHHAD data are primarily taken from references [1, 5], and from our own clinical experience, with additional references as listed in the table

PWS data are primarily taken from references [9–11], and from our own clinical experience, with additional references as listed in this Table