Non-syndromic familial congenital anorectal malformations

Gene: MYCN

Amber List (moderate evidence)

MYCN (MYCN proto-oncogene, bHLH transcription factor)
EnsemblGeneIds (GRCh38): ENSG00000134323
EnsemblGeneIds (GRCh37): ENSG00000134323
OMIM: 164840, Gene2Phenotype
MYCN is in 10 panels

2 reviews

Charles Shaw-Smith (Royal Devon and Exeter NHS Trust)

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Feingold syndrome

Eleanor Williams (Genomics England Curator)

Comment on list classification: Keep Amber rating as only 1 confirmed case of anal atresia and a variant in MYCN. Another case of a patient with Feingold syndrome 1 and anal atresia has been reported but no gene analysis.
Created: 1 Nov 2018, 2:34 p.m.
MYCN is associated with Feingold syndrome 1 in OMIM and a confirmed association with this disorder in Gene2Phenotype. Phenotypic features of this syndrome include variable combinations of microcephaly, limb malformations, esophageal and duodenal atresias, and learning disability/mental retardation.

Marcelis et al 2008 (PMID: 18470948) sequenced MYCN in 130 patients, 93 of which had a strong clinical suspicion of Feingold syndrome, the rest were missing some of the core features. 16 heterozygous mutations in MYCN were found in 26 patients from 17 families. All mutations either occurred de novo or segregated withthe disease in the family. Together with previous reports, a total of 23 separate MYCN mutations in 77 patients from 32 families have now been described. A total of 19 of the mutations create a stop codon or cause a frameshift. Out of 77 patients 55% showed atresias of the gastrointestinal tract. Esophageal atresia and duodenal atresia were almost equally frequent, 32 vs. 31%. Other atresias, jejunal or anal, are rare.

Marcelis et al 2008 report that previously, one case with anal atresia was published [Buttiker et al., 2000 (PMID: 10817649)] but with no molecular genetic analysis. Their present series includes one patient with this malformation and a variant in MYCN.
Created: 8 Oct 2018, 10:55 a.m.
Comment on list classification: Rating amber as is on expert list.
Created: 19 Sep 2018, 4:13 p.m.
Gene added from expert list from Dr Charles Shaw-Smith (Royal Devon and Exeter NHS Foundation Trust)
Created: 19 Sep 2018, 4:13 p.m.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
  • Expert list
Phenotypes
  • anorectal malformation
  • Feingold syndrome 1 164280
Tags
watchlist
OMIM
164840
Clinvar variants
Variants in MYCN
Penetrance
None
Publications
Panels with this gene

History Filter Activity

8 Nov 2018, Gel status: 2

Panel promoted to version 1.0

Eleanor Williams (Genomics England Curator)

Eleanor Williams: Gene added from expert list fr

8 Nov 2018, Gel status: 2

Added Tag

Eleanor Williams (Genomics England Curator)

Tag watchlist tag was added to gene: MYCN.

1 Nov 2018, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: mycn has been classified as Amber List (Moderate Evidence).

1 Nov 2018, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: mycn has been classified as Amber List (Moderate Evidence).

8 Oct 2018, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: MYCN were changed from anorectal malformation to anorectal malformation; Feingold syndrome 1 164280

8 Oct 2018, Gel status: 2

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: MYCN was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

8 Oct 2018, Gel status: 2

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: MYCN were set to

19 Sep 2018, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: mycn has been classified as Amber List (Moderate Evidence).

19 Sep 2018, Gel status: 1

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Added phenotypes anorectal malformation for gene: MYCN

19 Sep 2018, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Eleanor Williams (Genomics England Curator)

gene: MYCN was added gene: MYCN was added to Non-syndromic familial congenital anorectal malformations. Sources: Expert list Mode of inheritance for gene: MYCN was set to Phenotypes for gene: MYCN were set to anorectal malformation