FISH analysis demonstrated haploinsufficiency of HLXB9, a gene identified in the triad of a presacral mass (teratoma or anterior meningocele), sacral agenesis, and anorectal malformation, which constitutes the Currarino syndrome.
Our findings in the largest reported cohort to date significantly extend the range of reported manifestations associated with PIGV mutations and demonstrate that the severe end of the clinical spectrum presents as a multiple congenital malformation syndrome with a high frequency of Hirschsprung disease, vesicoureteral, and renal anomalies as well as anorectal malformations.
We reviewed the eight reported cases with proven PIGV mutations and re-defined the phenotypic spectrum associated with PIGV mutations: intellectual disability, the distinct facial gestalt, brachytelephalangy, and hyperphosphatasia are constant features but also anorectal malformations and Hirschsprung disease as well as cleft lip/palate and hearing impairment should be considered as part of the clinical spectrum.
These results support that missense mutation in the EBF2 c.215C > T (p.Ala72Val) is very likely to contribute to the pathogenesis of ARM in this family.
We compared the association of specific RET SNP alleles in patients with severe GI disorders such as anorectal malformation (ARM) or pediatric intestinal pseudo-obstruction (IPO) to that in HD patients.
We hypothesize that the urogenital and anorectal malformations in the patient result from one or several mechanisms including disruption of the genes 182-FIP and LHFPL5, altered expression of the genes flanking the translocation breakpoints and, a gain of function mechanism mediated by the 182-FIP-LHFPL5 fusion transcript.
We hypothesize that the urogenital and anorectal malformations in the patient result from one or several mechanisms including disruption of the genes 182-FIP and LHFPL5, altered expression of the genes flanking the translocation breakpoints and, a gain of function mechanism mediated by the 182-FIP-LHFPL5 fusion transcript.
Lack of folic acid supplement use in combination with infants or mothers carrying the MTHFRC677T polymorphism did not seem to increase the risk of ARM or subgroups of ARM.
This study shows that MOTA syndrome is caused by mutations in FREM1, a gene previously mutated in bifid nose, renal agenesis, and anorectal malformations (BNAR) syndrome.