1/18. A hirschsprung disease locus at 22q11?We report a boy with truncus arteriosus, dysmorphic features, developmental delay, passing hypotonia, short segment hirschsprung disease (HSCR), and paroxysmal hypoventilation. FISH analysis showed an interstitial deletion in chromosome band 22q11.2 coinciding with the deletions found in digeorge syndrome and velocardiofacial syndrome. mutation scanning of RET, GDNF, EDNRB, and EDN3, genes associated with hirschsprung disease, showed no aberrations. Since we know of two more patients with velocardiofacial syndrome and HSCR, we hypothesise that a gene responsible for proper development of the enteric nervous system may be included in the 22q11.2 region.- - - - - - - - - - ranking = 1keywords = nervous system (Clic here for more details about this article) |
2/18. Congenital hypomyelinating neuropathy, central dysmyelination, and Waardenburg-hirschsprung disease: phenotypes linked by SOX10 mutation.A unique phenotype of Waardenburg-hirschsprung disease (WS4) accompanied by peripheral neuropathy and central dysmyelination has been recognized recently in association with SOX10 mutations. We report an infant boy with lethal congenital hypomyelinating neuropathy and WS4 who had a heterozygous SOX10 mutation (Q250X). Histopathological studies showed an absence of peripheral nerve myelin despite normal numbers of schwann cells and profound dysmyelination in the central nervous system. These observations suggest that some SOX10 mutations such as Q250X may allow schwann cells and oligodendrocytes to proliferate but interfere with further differentiation to form myelin. In contrast with the SOX10 loss-of-function mutations causing only WS4, mutations associated with both peripheral and central dysmyelination may affect pathology through a dominant-negative mechanism.- - - - - - - - - - ranking = 1.1538863849983keywords = nervous system, central nervous system (Clic here for more details about this article) |
3/18. PMX2B, a new candidate gene for Hirschsprung's disease.Hirschsprung's (HSCR) disease is a congenital intestinal malformation of the enteric nervous system. It is a multigenic malformation and until now, eight genes have been involved in the etiology of this disease: genes encoding proteins of the RET signaling pathway (RET, GDNF and NTN), genes participating in the endothelin (EDN) type B receptor pathway (EDNRB, EDN3 and ECE-1), the SOX10 gene and the SIP1 gene that is mutated in syndromic forms of HSCR. Mutations of these genes are found in not more than 50-60% of affected individuals. Here, we report on the results of a molecular cytogenetic study performed in a girl who presented with a syndromic short segment HSCR associated with a de novo t(4;8)(p13;p22) translocation. A comparative genomic hybridization (CGH) study found a 4p12p13 deletion. A molecular characterization of this rearrangement showed that the 4p13 deletion was 5 Mb in length and included the paired mesoderm homeobox gene (PMX2B) (MIM 603851), a gene expressed in the human embryonic gut and essential for the development of autonomic neural crest derivatives. The present observation suggests that PMX2B haploinsuffciency might predispose to HSCR.- - - - - - - - - - ranking = 1keywords = nervous system (Clic here for more details about this article) |
4/18. Plasticity of the enteric nervous system in patients with intestinal neuronal dysplasia associated with Hirschsprung's disease: a report of three patients.Intestinal neuronal dysplasia is a controversial form of dysganglionosis that has been described both as an isolated disorder and in association with Hirschsprung's disease. It has been blamed for the bad outcome of bowel function in patients operated on for Hirschsprung's disease. According to various authors, intestinal neuronal dysplasia could be a primary disorder or secondary to other diseases of the bowel. The aim of this study was to assess the plasticity of the enteric nervous system in patients with Hirschsprung's disease-associated intestinal neuronal dysplasia and its ability to evolve spontaneously to normal innervation patterns. Since we prospectively introduced the assessment of the enteric nervous system of the ganglionated bowel in patients operated on for Hirschsprung's disease, 31 patients have been operated on for Hirschsprung's disease in our institution between 1995 and 2002. Among these patients, nine suffered postoperatively from severe constipation and five from bouts of entocolitis. IND was found in eight of them. We studied the evolution of the innervation in three of these patients by repeated serial full-thickness biopsies of the colon. All three patients underwent a colostomy before or after the pull-through procedure. Histopathological assessment of the enteric nervous system was made with conventional acetylcholinesterase histochemistry, rapid acetylcholinesterase histochemistry and immunohistochemistry for the Protein Gene Product 9.5 and the antigen CD56. This evolution was compared with the clinical outcome of bowel function. In our three patients with Hirschsprung's disease-associated intestinal neuronal dysplasia, this form of dysganglionosis evolved to normal innervation patterns within a period ranging from 9 to 18 months. This evolution was accompanied by an improvement of bowel function in all. We conclude that Hirschsprung's disease-associated intestinal neuronal dysplasia can evolve to a normal innervation, at least under certain circumstances such as a colostomy. Specific histopathological techniques are required to assess accurately the enteric nervous system.- - - - - - - - - - ranking = 8keywords = nervous system (Clic here for more details about this article) |
5/18. mortality due to constipation and short-segment Hirschsprung's disease.We report a case of mortality secondary to constipation. A 12-year-old child with a history of constipation from the age of 9 years presented in moribund condition with intestinal obstruction secondary to idiopathic constipation. He underwent laparotomy and died within 24 h of operation. At postmortem there was no evidence of abnormalities of the enteric nervous system. A 2nd case of early neonatal death from Hirschsprung's disease is presented to demonstrate that short-segment aganglionosis can be detected at postmortem. enterocolitis can rapidly progress and be fatal in short-segment Hirschsprung's disease.- - - - - - - - - - ranking = 1keywords = nervous system (Clic here for more details about this article) |
6/18. Congenital central hypoventilation syndrome and Hirschsprung's disease in an extremely preterm infant.Congenital central hypoventilation syndrome with Hirschsprung's disease, also known as Haddad syndrome, is a rare disorder with a variable phenotypic severity. The underlying cause is thought to be an abnormality of neural crest development and/or migration. Surviving neonates can have generalized autonomic nervous system dysfunction. Recent reports have identified mutations in the PHOX2B gene in a significant number of patients with this disorder. diagnosis and management of this disorder in the setting of extreme prematurity is difficult as the manifestations of failure to maintain breathing effort and failure to establish feeds overlap with the complications of prematurity. We describe an infant who had congenital central hypoventilation syndrome with Hirschsprung's disease and was delivered at 26 weeks' gestational age and had total aganglionosis of the bowel, failure to wean from ventilation, and a mutation in the PHOX2B gene.- - - - - - - - - - ranking = 1keywords = nervous system (Clic here for more details about this article) |
7/18. megacolon in adulthood after surgical treatment of Hirschsprung's disease in early childhood.Hirschsprung's disease (HD) is a disorder associated with congenital malformation of the enteric nervous system with segmental aganglionosis. Prevailing therapy includes a resection of the affected part of the bowel. However, patients often do not obtain complete functional improvement after surgical treatment. We present the case of a 25-year-old woman who had surgical treatment of HD in early childhood. After that procedure she had clinical features of constipation for years in the end, passing of stool once a week, requiring laxatives and enemas. We diagnosed an incomplete resection of the aganglionic bowel via rectal biopsy and resected the remaining aganglionic segment. Two months after surgery the patient's bowel function improved to a frequency of 1-4 stools per day. We conclude that regular follow-up is required to identify HD patients with persistent alterations of bowel function after surgery. In patients presenting with constipation, recognition of a remaining aganglionic segment or other alterations of the enteric nervous system should be aimed at in an early stage.- - - - - - - - - - ranking = 2keywords = nervous system (Clic here for more details about this article) |
8/18. Shah-waardenburg syndrome and PCWH associated with SOX10 mutations: a case report and review of the literature.Shah-waardenburg syndrome is a rare congenital disorder with variable clinical expression, characterised by aganglionosis of the rectosigmoid (hirschsprung disease), and abnormal melanocyte migration, resulting in pigmentary abnormalities and sensorineural deafness (waardenburg syndrome). Mutations in the EDN, EDNRB and SOX10 genes can be found in patients with this syndrome. SOX10 mutations are specifically associated with a more severe phenotype called PCWH: peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, waardenburg syndrome, and hirschsprung disease. Neuronal expression of SOX10 occurs in neural crest cells during early embryonic development and in glial cells of the peripheral and central nervous systems during late embryonic development and in adults. We present a 4-year-old girl with the PCWH phenotype associated with a de novo nonsense mutation (S384X) in SOX10. Main clinical features were mental retardation, peripheral neuropathy, deafness, hirschsprung disease, distal arthrogryposis, white hairlock, and growth retardation. She presented with hypotonia, developmental delay, reduced peripheral nerve conduction velocities, and radiologically assessed central hypomyelination. Subsequently, the formation of abnormal myelin within the central and peripheral nervous system was functionally and radiologically assessed. Children presenting with features of waardenburg syndrome and neurological dysfunction should be tested for mutations in the SOX10 gene to enable diagnosis and counselling.- - - - - - - - - - ranking = 2.1538863849983keywords = nervous system, central nervous system (Clic here for more details about this article) |
9/18. Case report of Haddad syndrome in a newborn: congenital central hypoventilation syndrome and Hirschsprung's disease.Congenital central hypoventilation syndrome (CCHS) is a rare disorder characterized by failure of automatic control of breathing. diagnosis is made by exclusion of other causes of hypoventilation. Genetic etiology is strongly suspected. Other autonomic nervous system dysfunctions, tumors of neural crest origin and Hirschsprung's disease are often found in affected children. association with Hirschsprung's disease is known as Haddad syndrome. We present a newborn with respiratory distress since birth and Hirschprung's disease subsequently diagnosed with Haddad syndrome.- - - - - - - - - - ranking = 1keywords = nervous system (Clic here for more details about this article) |
10/18. A De Novo novel mutation of the EDNRB gene in a Taiwanese boy with hirschsprung disease.hirschsprung disease (HSCR) is a congenital disorder characterized by an absence of ganglion cells in the nerve plexuses of the lower digestive tract. Although mutations in eight different genes (EDNRB, EDN3, ECE1, SOX10, RET, GDNF, NTN, SIP1) have been identified in affected individuals, it is now clear that RET and EDNRB are the primary genes implicated in the etiology of HSCR. All eight genes are involved in the early development of the enteric nervous system, and most act through two distinct biochemical pathways mediated by RET and EDNRB. Mutations in RET and EDNRB account for up to 50% and 5% of HSCR cases in the general population, respectively. Interaction between these two signaling pathways could modify RET expression and, therefore, HSCR phenotype. Here, we report the case of a 1-year-old Taiwanese boy who presented with abdominal distension since birth and bilious vomiting after feeding. HSCR (short-segment type) was diagnosed based on X-ray, lower gastrointestinal series and biopsy findings. mutation analysis revealed a heterozygous T>C missense mutation in exon 1 of the EDNRB gene, that substitutes the highly conserved cysteine-90 residue in the extracellular domain of the G protein-coupled receptor with an arginine residue (C90R). No RET gene mutation was detected in this patient.- - - - - - - - - - ranking = 1keywords = nervous system (Clic here for more details about this article) |
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