pecific mutations were identified.

The observation of monozygotic twins discordant for the ROHHAD

phenotype could be consistent with a somatic genetic mutation, but

could also suggest an alternative, nongenetic etiology. For example,

epigenetic variation can account for some discordance between mono-

zygotic twins and also can play a role in diseases involving respiratory

and autonomic function, such as Prader-Willi syndrome (see later) and

Rett syndrome.

Paraneoplastic/Autoimmune Hypothesis

Paraneoplastic syndromes are rare disorders caused by a neoplasm trig-

gering an altered immune response that aberrantly attacks and destroys

neurons, leading to the nervous system symptoms. An autoimmune

or paraneoplastic basis for ROHHAD has been suggested based on

neural crest tumors occurring in 40% of ROHHAD patients and 2 early

cases with autopsies revealing low-density lesions in the basal ganglia

and neuronal loss from lymphocytic infiltration of the hypotha