Dp71 and intellectual disability in Indonesian patients with Duchenne muscular dystrophy.

INTRODUCTIONS: Duchenne muscular dystrophy (DMD) is an X-linked recessive progressive muscular disease marked by developmental delays due to mutations in the DMD gene, which encodes dystrophin. Brain comorbidity adds to the burden of limited mobility and significantly impacts patients' quality of life and their family. The changes of expression of dystrophin isoforms in the brain due to DMD gene mutations are thought to be related to the cognitive and neurobehavior profiles of DMD. OBJECTIVES: This cross-sectional study aimed to characterize cognitive and neurodevelopmental profiles of patients with DMD and to explore underlying genotype-phenotype associations. METHODS: Patients with DMD aged 5-18 years from Dr Sardjito Hospital and Universitas Gadjah Mada Academic Hospital from 2017-2022 were included. Multiplex ligation-dependent probe amplification and whole exome sequencing were used to determine mutations in the DMD genes. Cognitive function was measured by intelligence quotient testing using the Wechsler Intelligence Scale for Children and adaptive function tests with Vineland Adaptive Behavior Scales. The Autism Mental Status Exam and Abbreviated Conner's Rating Scale were used to screen for autism spectrum disorder (ASD) and attention deficit and hyperactivity disorder (ADHD), respectively. RESULTS: The mean total IQ score of DMD patients was lower than that of the general population (80.6 ± 22.0 vs 100 ± 15), with intellectual disability observed in 15 boys (29.4%). Of the 51 patients with DMD, the Dp71 group had the lowest cognitive performance with a total IQ score (46 ± 24.8; p = 0.003), while the Dp427 group and Dp140 group's total IQ scores were 83.0 ± 24.6 and 84.2 ± 17.5 respectively. There were no DMD patients with ASD, while 4 boys (7.8%) had comorbidity with ADHD. CONCLUSION: Boys with DMD are at higher risk of intellectual disability. The risk appears to increase with mutations at the 3' end of the gene (Dp71 disruption). Moreover, Dp71 disruption might not be associated with ADHD and ASD in patients with DMD.

Functional outcomes of patients with short-segment Hirschsprung disease after transanal endorectal pull-through.

BACKGROUND: Transanal endorectal pull-through (TEPT) is considered the most preferable treatment method for Hirschsprung disease (HSCR) since it is less invasive and has fewer morbidities than transabdominal pull-through. Here, functional outcomes in short-segment HSCR patients after TEPT were assessed and associated with the prognostic factors. METHODS: Krickenbeck classification was used to assess the functional outcomes in patients with HSCR after TEPT surgery at our institution from 2012 to 2020. RESULTS: Fifty patients were involved in this study. Voluntary bowel movement (VBM) was achieved in 82% of subjects. Nine (18%) subjects had soiling grade 1, while two (4%) and two (4%) patients suffered constipation that was manageable with diet and laxative agents, respectively. Patients who underwent TEPT at ≥ 4 years old tended to have soiling more than patients who underwent TEPT at < 4 years old (OR = 16.47 [95% CI 0.9-301.61]; p = 0.06), whereas patients with post-operative complications had 10.5-fold higher risk for constipation than patients without post-operative complications (p = 0.037; 95% CI 1.15-95.92). Multivariate analysis showed male sex was significantly associated with VBM (OR = 9.25 [95% CI 1.34-63.77]; p = 0.024), while post-operative complications were strongly correlated with constipation (OR = 10 [95% CI 1.09-91.44]; p = 0.04). CONCLUSIONS: The functional outcomes of HSCR patients after TEPT in our institution are considered relatively good. Moreover, the VBM, soiling, and constipation risk after TEPT might be affected by sex, age at TEPT performed, and post-operative complications, respectively, while the age at TEPT performed might not be associated with functional outcomes. Further multicenter studies with a larger sample size are necessary to clarify and confirm our findings.