Rett syndrome is a
neurodevelopmental disorder, which occurs in about 1:15,000 females and presents with neurologic and communication defects. It is transmitted as an X-linked dominant linked to mutations of the methyl-CpG-
binding protein (MeCP2), a gene transcription suppressor, but its definitive pathogenesis is unknown thus hindering development of effective treatments. Almost half of children with
Rett syndrome also have behavioral symptoms consistent with those of
autism spectrum disorders (ASDs). PubMed was searched (2005-2014) using the terms:
allergy, atopy, brain,
brain-derived neurotrophic factor (
BDNF),
corticotropin-releasing hormone (CRH),
cytokines, gene mutations,
inflammation, mast cells (MCs), microglia, mitochondria,
neurotensin (NT),
neurotrophins,
seizures, stress, and treatment. There are a number of intriguing differences and similarities between
Rett syndrome and ASDs.
Rett syndrome occurs in females, while ASDs more often in males, and the former has neurologic disabilities unlike ASDs. There is evidence of dysregulated immune system early in life in both conditions. Lack of microglial phagocytosis and decreased levels of
BDNF appear to distinguish
Rett syndrome from ASDs, in which there is instead microglia activation and/or proliferation and possibly defective
BDNF signaling. Moreover, brain mast cell (MC) activation and focal
inflammation may be more prominent in ASDs than
Rett syndrome. The
flavonoid luteolin blocks microglia and MC activation, provides
BDNF-like activity, reverses Rett phenotype in mouse models, and has a significant benefit in children with ASDs. Appropriate formulations of
luteolin or other natural molecules may be useful in the treatment of
Rett syndrome.