Generalized linear univariate model analysis performed on the opiate-induced constipation-associated SNPs and a single CHRM3 SNP revealed an association between anticholinergic symptoms and a score of 8 SNPs (adjusted P = 0.038, permuted P = 0.002).
Larger numbers of patients need to be studied to investigate whether low SP is primarily associated with the constipation or RET mutation and if it is a common feature of MEN 2B.
Given that one putative FG locus (FGS2) is situated at Xq28, which is the location of the Filamin A gene (FLNA), and that a Filamin A mutation was reported in a boy with facial dysmorphism and constipation, it was hypothesized that Filamin A mutations could be one cause of FG syndrome.
The second positive AM case, a 69-year-old white man who presented with painless rectal bleeding and clinical symptoms of an intestinal constipation showed a novel missense mutation (C1327T leading to R443W conversion) in BRAF exon 11.
Rett syndrome (RTT), a progressive neurological disorder mainly caused by mutations in MeCP2 gene, is commonly associated with gastrointestinal dysfunctions and constipation, suggesting a link between RTT's gastrointestinal abnormalities and the gut microbiota.
Conclusions This exploratory study found low serum levels of 5-HT to be associated with constipation and the presence of TPH-1 and AADC Aabs, but not with symptoms of depression.
Recommended management options aimed toward maximizing safety and optimizing neurocognitive outcome include: (1) biannual then annual in-hospital comprehensive evaluation with (i) physiologic studies during awake and asleep states to assess ventilatory needs during varying levels of activity and concentration, in all stages of sleep, with spontaneous breathing, and with artificial ventilation, and to assess ventilatory responsiveness to physiologic challenges while awake and asleep, (ii) 72-hour Holter monitoring, (iii) echocardiogram, (iv) evaluation of ANS dysregulation across all organ systems affected by the ANS, and (v) formal neurocognitive assessment; (2) barium enema or manometry and/or full thickness rectal biopsy for patients with a history of constipation; and (3) imaging for neural crest tumors in individuals at greatest risk based on PHOX2B mutation.