Fryns syndrome with Hirschsprung disease: Support for possible neural crest involvement

Alkuraya, Fowzan S.; Lin, Angela E.; Irons, Mira; Kimonis, Virginia

doi:10.1002/ajmg.a.30423

Cited by 13 publications

(6 citation statements)

References 35 publications

(50 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Muscular anomalies associated with HSCR include muscular dystrophy [66]. In addition, Fryns syndrome with diaphragmatic hernias [67] and distal limb anomalies [67] may be associated with HSCR. Distal limb abnormalities are largely represented by polydactyly and limb hypoplasia but may also be associated with congenital deafness [68] or cardiac anomalies [69,70].…”

Section: Intestinal Atresiamentioning

confidence: 98%

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

Moore

2006

Ped Surgery Int

View full text Add to dashboard Cite

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.

show abstract

Section: Intestinal Atresiamentioning

confidence: 98%

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

Moore

2006

Ped Surgery Int

View full text Add to dashboard Cite

show abstract

“…Also several other authors described cases of skeletal or limb anomalies in different syndromes associated with Hirschsprung disease. For example, Alkuraya et al (47) reported about a newborn girl with Fryns syndrome (multiple congenital anomalies characterized also by distal limb hypoplasia) associated with HSCR, and Goldenberg et al (48) reported a case of absence of tibiae and polysyndactyly of hands and feet associated with HSCR.…”

Section: Hirschsprung Disease and Skeletal Limb And Digital Anomaliesmentioning

confidence: 99%

An embryological point of view on associated congenital anomalies of children with Hirschsprung disease

Slavikova¹,

Zabojnikova²,

J³

et al. 2015

BLL

View full text Add to dashboard Cite

The most common congenital gut motility disorder is the Hirschsprung disease (HSCR). This anomaly is characterized by absence of neural crest-derived enteric neuronal ganglia. The aim of our study was to analyze the relationship between HSCR and other congenital anomalies or malfunctions. We examined 130 patients with Hirschsprung disease from Slovakia for last 10 years. During patients examination we focused not only on morphological abnormalities, but also functional anomalies. The incidence of associated congenital anomalies in our patients with HSCR was 26.1 %. But if we add functional defects (hypothyroidism, malfunction in cellular immunity, neurological defi cit) to the morphological congenital abnormalities, the rate of the patients with HSCR with additional defects achieves 50.1 %. Nine of our patients (6.9 %) had syndromic HSCR. The most frequent disorder (13.6 % of patients) was primary defi ciency in cellular immunity. More than 12.3 % of patients with HSCR had genitourinary abnormalities, in 10.0 % of patients variable degree of psychomotor retardation was observed, and skeletal, muscle and limb anomalies involved 7.7 % of patients. In 7.6 % cases of patients we found congenital hypothyroidism (including 2 cases of agenesis of thyroid gland). More than 6.1 % of patients presented with an associated anomaly in gastrointestinal tract (mostly anorectal malformations). Up to 5.5 % patients had congenital anomaly of heart, 3.8 % had ophthalmic and 3.1 % had craniofacial anomalies. Down syndrome was the main diagnosis in 3.8 % patients. We discussed the relationship between HSCR and other anomalies, which are probably caused by abnormal migration, proliferation, or differentiation, of neural crest cells during embryogenesis (Tab. 1, Fig. 2, Ref. 75). Text in PDF www.elis.sk.

show abstract

“…It is possible that TBX1 is involved in the pathogenesis of CDH in 22q11.2DS. Neural crest‐derived defects, such as conotruncal cardiovascular malformations, have also been described in the nitrofen CDH rat model [Yu et al, ] and in Fryns syndrome [Alkuraya et al, ; Lin et al, ]. This provides additional support for an etiologic role of genes related to neural crest cell development in the pathogenesis of CDH.…”

Section: Discussionmentioning

confidence: 90%

Congenital diaphragmatic hernia in 22q11.2 deletion syndrome

Unolt

DiCairano

Schlechtweg

et al. 2016

American J of Med Genetics Pt A

View full text Add to dashboard Cite

We report the important association of congenital diaphragmatic hernia (CDH) and 22q11.2 deletion syndrome (22q11.2DS). The prevalence of CDH in our cohort of patients with 22q11.2DS is 0.8% (10/1246), which is greater than in the general population (0.025%). This observation suggests that 22q11.2DS should be considered when a child or fetus presents with CDH, in particular when other clinical findings associated with the 22q11.2DS are present, such as congenital cardiac defects. Furthermore, this finding may lead to the identification of an additional locus for diaphragmatic hernia in the general population. © 2016 Wiley Periodicals, Inc.

show abstract

Fryns syndrome with Hirschsprung disease: Support for possible neural crest involvement

Cited by 13 publications

References 35 publications

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

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

An embryological point of view on associated congenital anomalies of children with Hirschsprung disease

Congenital diaphragmatic hernia in 22q11.2 deletion syndrome

Contact Info

Product

Resources

About