Hirschsprung disease, postaxial polydactyly, and atrial septal defect

Nowaczyk, Małgorzata J.M.; James, Arthur G.; Ra, Superina; Siegel‐Bartelt, J.

doi:10.1002/(sici)1096-8628(19970110)68:1<74::aid-ajmg14>3.0.co;2-l

Cited by 6 publications

(4 citation statements)

References 17 publications

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“…Septation defects (ASD/VSD) [76] and conotruncal developmental defects [3] appear the most frequent. This is understandable as the critical stage of cardiac development occurs at more or less the same time as the enteric nervous system and is dependent on neural crest cell proliferation which in turn links them with neurocristopathies.…”

Section: Intestinal Atresiamentioning

confidence: 99%

The contribution of associated congenital anomalies in understanding Hirschsprung’s disease

Moore

2006

Ped Surgery Int

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Hirschsprung's disease (HSCR) is a complex congenital disorder which, from a molecular perspective, appears to result due to disruption of normal signalling during development of enteric nerve cells, resulting in aganglionosis of the distal bowel. Associated congenital anomalies occur in at least 5-32% (mean 21%) of patients and certain syndromic phenotypes have been linked to distinct genetic sites, indicating underlying genetic associations of the disease and probable gene-gene interaction in its pathogenesis. Clear-cut associations with HSCR include Down's syndrome, dominant sensorineural deafness, Waardenburg syndrome, neurofibromatosis, neuroblastoma, phaeochromocytoma, the MEN type IIB syndrome and other abnormalities. Individual anomalies vary from 2.97% to 8%, the most frequent being the gastrointestinal tract (GIT) (8.05%), the central nervous system (CNS) and sensorineural anomalies (6.79%) and the genito-urinary tract (6.05%). Other associated systems include the musculoskeletal (5.12%), cardiovascular systems (4.99%), craniofacial and eye abnormalities (3%) and less frequently the skin and integumentary system (ectodermal dysplasia) and syndromes related to cholesterol and fat metabolism. In addition to associations with neuroblastoma and tumours related to MEN2B, HSCR may also be associated with tumours of neural origin such as ganglioneuroma, ganglioneuroblastoma, retinoblastoma and tumours associated with neurofibromatosis and other autonomic nervous system disturbances. The contribution of the major susceptibility genes on chromosome 10 (RET) and chromosome 13 (EDNRB) is well established in the phenotypic expression of HSCR. Whereas major RET mutations may result in HSCR by haploinsufficiency in 20-25% of cases, the etiology of the majority of sporadic HSCR is not as clear, appearing to arise from the combined cumulative effects of susceptibility loci at critical genes controlling the mechanisms of cell proliferation, differentiation and maturation. In addition, potential "modifying" associations exist with chromosome 2, 9, 20, 21 and 22, and we explore the importance of certain flanking genes of critical areas in the final phenotypic expression of HSCR.

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Section: Intestinal Atresiamentioning

confidence: 99%

The contribution of associated congenital anomalies in understanding Hirschsprung’s disease

Moore

2006

Ped Surgery Int

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“…Trisomy 21 Unknown DiGeorge Syndrome 290 Unknown BRESHECK association 291 Unknown (X-linked) Postaxial polydactyly and heart defect 292,293 Unknown Goldberg-Shprintzen Syndrome [294][295][296][297][298] Unknown Hemimegalencephaly 299 Unknown Congenital muscular dystrophy 300 Unknown enon is partially explained by the fact that many "HSCR gene" products influence the behavior of diverse neural crest cell derivatives in addition to vagal crest cells. Waardenburg syndrome type 4 (WS4, Waardenburg-Shah syndrome) is a generalized neurocristopathy in which HSCR is a diagnostic feature.…”

Section: Congenital Defects Associated With Hscrmentioning

confidence: 99%

Hirschsprung Disease and Other Enteric Dysganglionoses

Kapur

1999

Critical Reviews in Clinical Laboratory Sciences

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Hirschsprung disease has become a paradigm for multigene disorders because the same basic phenotype is associated with mutations in at least seven distinct genes. As such, the condition poses distinct challenges for clinicians, patients, diagnostic pathologists, and basic scientists, who must cope with the implications of this genetic complexity to comprehend the pathogenesis of the disorder and effectively manage patients. This review focuses on the anatomic pathology, genetics, and pathogenesis of Hirschsprung disease and related conditions. The nature and functions of "Hirschsprung disease genes" are examined in detail and emphasis is placed on the importance of animal models to this field. Where possible, potential uses and limitations of new data concerning molecular genetics and pathogenesis are discussed as they relate to contemporary medical practices.

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“…Moreover, activation and loss of function in the same gene cause different phenotypic outcomes such as in the RET proto-oncogene in which loss of function mutations are associated with familial Hirschsprung disease [15,16]. There have been multiple articles with Hischsprung disease with other congenital associations [17][18][19][20][21][22]. The clinical manifestations of TBS are highly variable and show strong inter-and intrafamilial variability [14].…”

Section: Resultsmentioning

confidence: 99%

Two Novel Mutations in SALL1 Cause Townes-Brocks-Like Syndrome: New Findings from an Old Case

Sun¹,

Bove²,

Zou³

et al. 2019

Genet Mol Med

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Background: All previous genetic testing has failed to identify the genetic cause of syndrome affecting this family for nearly 20 years. The advent of massively parallel next-generation sequencing technologies has provided an opportunity to affordably screen exomes to establish the genetic basis of disease. The utility of whole exome sequencing to identify causative variants of Mendelian disorders has been clearly demonstrated in the research arena. In this report, we describe a family with unique clinical features, including Hirschsprung disease, with a suspected genetic basis. Methods: We employed whole exome sequencing to this case to identify causative mutations. Results: We identified two novel compound heterozygous variants, following an autosomal recessive mode of inheritance, in the candidate gene SALL1, a gene known to cause Townes-Brocks syndrome (TBS) and central nervous system TBS (CNS-TBS). The pathogenicity of the two variants was supported by co-segregation, low frequency, location in mutation hotspot, pathogenicity program predictions, phenotype similarity, and immunohistochemical staining. As previously reported, we observed intrafamilial phenotypic variability among the affected individuals and they may represent an expansion of TBS, CNS-TBS or a new CNS-TBS-like syndrome by observing atypical features in affected individuals including mental retardation, developmental delay, tracheal anomalies, Hirschsprung disease and cleft lip and palate. Conclusion: Solving this case brought a new view of the genetics of TBS and its relationship with SALL1. Another lesson learned is that advanced technologies have a profound impact on old, unsolved cases such as the one presented here. Thus, we further demonstrated the utility of exome sequencing in the research arena.

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Hirschsprung disease, postaxial polydactyly, and atrial septal defect

Cited by 6 publications

References 17 publications

The contribution of associated congenital anomalies in understanding Hirschsprung’s disease

The contribution of associated congenital anomalies in understanding Hirschsprung’s disease

Hirschsprung Disease and Other Enteric Dysganglionoses

Two Novel Mutations in SALL1 Cause Townes-Brocks-Like Syndrome: New Findings from an Old Case

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