Four new loci associations discovered by pathway-based and network analyses of the genome-wide variability profile of Hirschsprung’s disease

Migraine is a common, chronic neurovascular disorder caused by a complex interaction between genetic and environmental risk factors. In the last two decades, molecular genetics of migraine have been intensively investigated. In a few cases, migraine is transmitted as a monogenic disorder, and the disease phenotype cosegregates with mutations in different genes like CACNA1A, ATP1A2, SCN1A, KCNK18, and NOTCH3. In the common forms of migraine, candidate genes as well as genome-wide association studies have shown that a large number of genetic variants may increase the risk of developing migraine. At present, few studies investigated the genotype-phenotype correlation in patients with migraine. The purpose of this review was to discuss recent studies investigating the relationship between different genetic variants and the clinical characteristics of migraine. Analysis of genotype-phenotype correlations in migraineurs is complicated by several confounding factors and, to date, only polymorphisms of the MTHFR gene have been shown to have an effect on migraine phenotype. Additional genomic studies and network analyses are needed to clarify the complex pathways underlying migraine and its clinical phenotypes.

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Outcomes in Hirschsprung’s disease with coexisting learning disability

European Journal of Pediatrics ◽

10.1007/s00431-021-04129-5 ◽

2021 ◽

Author(s):

Joseph R. Davidson ◽

Kristiina Kyrklund ◽

Simon Eaton ◽

Mikko P. Pakarinen ◽

David Thompson ◽

...

Keyword(s):

Quality Of Life ◽

Learning Disability ◽

Hirschsprung's Disease ◽

Hirschsprung’S Disease ◽

Core Outcome Set ◽

Functional Results ◽

Cross Sectional Study ◽

Cross Sectional ◽

Related Quality

AbstractThis study describes functional and health-related quality of life (HRQoL) outcomes in patients with Hirschsprung’s disease (HSCR) with associated learning disability or neurodevelopmental delay (LD), completing a core outcome set for HSCR. This was a cross-sectional study from a tertiary pediatric surgery center. Patients treated between 1977 and 2013 were prospectively contacted to complete an outcomes survey. Children under 12 and older patients with LD were assisted to complete these by a proxy. Bowel and urologic function were assessed (Rintala’s BFS and modified DanPSS) along with HRQoL (PedsQL/GIQLI/SF-36). Thirty-two patients with LD were compared to 186 patients with normal cognition. Patients with LD had 76% survival over the follow-up period, compared to 99% in the remainder of the cohort. Poor functional outcomes were common in the patients with LD, considerably higher than cognitively normal patients: with weekly issues withholding stool, soiling and fecal accidents in over half of patients surveyed (44–60%), and urinary incontinence in 46%. Use of permanent stoma was significantly higher (22% vs. 4%; p = 0.001). HRQoL was worse in domains of physical functioning in adults and children but not for social or emotional domains in adults. Subgroup analysis of patients with Down syndrome suggested similar functional results but better QoL. Multivariate analysis demonstrated a dramatically higher incidence of poor continence outcomes in patients with LD (adjusted OR 9.6 [4.0–23]).Conclusions: We provide LD-specific outcomes showing inferior function but similar HRQoL to other patients with HSCR, this is much needed in the counselling of families of these children. What is Known:• Hirschsprung’s disease is commonly associated with syndromes or other anomalies with resultant cognitive impairments.• The outcomes for these patients specifically have been poorly described in the literature. What is New:• Objective functional and quality of life surveys demonstrate significant differences from patients without cognitive impairment.• Patients with learning disability Patients with associated LD were almost ten times more likely to have an associated poor functional outcome, with very little impact on proxy-reported quality of life.

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