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The gastrointestinal tract
Published in Angus Clarke, Alex Murray, Julian Sampson, Harper's Practical Genetic Counselling, 2019
The underlying cause of Hirschsprung disease should be considered. It may be (1) chromosomal, in about 12% of cases, with the most frequent single condition being Down syndrome. Then (2) there are the monogenic, syndromic forms. Hirschsprung disease is a significant complication of Mowat-Wilson syndrome and FG syndrome and is also a feature of Bardet-Biedl syndrome, congenital central hypoventilation, cartilage hair hypoplasia, Goldberg-Shprintzen syndrome and Waardenburg syndrome type 4 (among others). (3) There are the monogenic non-syndromic forms, associated especially with variants of low penetrance in the RET proto-oncogene but variants in other genes can be associated (including EDN3 and EDNRB). Pathogenic variants in RET act as a Mendelian predisposition to the condition but are not sufficient to cause it. Then, finally (4) there are those cases that are non-syndromic but without a recognised molecular predisposition.
Total colonic Hirschsprung disease: Ileo-Duhamel
Published in Alejandra Vilanova-Sánchez, Marc A. Levitt, Pediatric Colorectal and Pelvic Reconstructive Surgery, 2020
Jonathan H. Sutcliffe, Alejandra Vilanova-Sánchez, Jacob C. Langer
To discuss Timing of surgery; ensure that the child is thriving, has an ileostomy output of <20 mL/kg and with an appropriate stool consistency (apple sauce). Ensure the home environment is as stable as possible. From 8 to 12 months is a good rule of thumb [6].All infants with an ileostomy require sodium supplementation. Adequacy of supplementation can be monitored by maintaining a urine sodium > 25 mEq [7].A range of procedures have been undertaken often with similar results. The experience of the surgeon and the institution is an important factor. A “straight” Swenson or Duhamel pull-through would be the most common currently. Although different modifications have been tried, the Duhamel pouch should be short. J-Pouches have also been used [8].The colon patch procedures (Martin and Kimura) are usually associated with late complications including chronic enterocolitis and poor emptying, and in most cases are not recommended [9].Discuss long term outcomes candidly with the family. In addition to the complications of surgery for short segment disease, long segment disease is associated with an increased risk of high output, perianal excoriation, soiling, HD-associated enterocolitis and HD-associated inflammatory bowel disease.There are some patients for whom a long-term stoma is best. Many patients with aganglionosis extending well into the small bowel, with resultant short bowel syndrome have persistently loose, high output effluent. Other patients may have significant co-morbidity such that continence would be unlikely e.g., Mowat-Wilson syndrome, associated high anorectal malformation, and a pull-through would not confer any benefit. Acceptable outcomes in children with Down syndrome have however been reported, and careful discussion with families is required [10].
Interleukin-10 restores glutamate receptor-mediated Ca2+-signaling in brain circuits under loss of Sip1 transcription factor
Published in International Journal of Neuroscience, 2021
Maria V. Turovskaya, Ekaterina A. Epifanova, Victor S. Tarabykin, Alexei A. Babaev, Egor A. Turovsky
Sip1 (Zeb2) is a transcription factor that is involved in the regulation of neurogenesis, and it mostly acts as a transcriptional repressor. Mutations of the Sip1 gene in humans lead to the development of various pathologies, including Hirschsprung's disease and Mowat–Wilson syndrome [1–3]. The most common signs of Mowat–Wilson syndrome are prenatal and postnatal microcephaly (identified in 97% of cases), epileptic seizures (82% of cases), Hirschsprung's disease (68%), congenital heart disease (47%), and agenesis of corpus callosum (29%). At the same time, mental retardation and craniofacial disorders are observed in 100% of cases of this syndrome [4].