Table 4. [Associated Findings in Individuals with BWS by Molecular Mechanism]. - GeneReviews®

Molecular Mechanism	Associated Findings	Comments
Loss of methylation at IC2 (maternal)	Lower risk for tumor development overall (~3%)	Higher risk for hepatoblastoma than for WT
Hemihyperplasia may be observed.
Positive family history in those w/genomic alterations at IC2	Rare
Omphalocele
Brain malformations involving posterior fossa	Rare
Female monozygotic twinning discordant for BWS	Male monozygotic twinning is far less frequent & is assoc w/range of molecular alterations.
History of subfertility / use of ART to achieve pregnancy ¹	In parents of affected person
Gain of methylation at IC1 (maternal)	One of the highest risks for WT
Hemihyperplasia may be observed.
Positive family history in those w/deletion of IC1
Paternal UPD	One of the highest risks for WT & hepatoblastoma
More commonly assoc w/hemihyperplasia	Particularly when paternal UPD is mosaic
Severe BWS phenotype	When due to high levels of somatic mosaicism of paternal UPD
*Heterozygous maternal CDKN1C* pathogenic variants**	Assoc w/neuroblastoma & single cases of ganglioneuroblastoma, ganglioneuroma, acute lymphocytic leukemia in children, & melanoma in an adult ²	Given that leukemia & melanoma occur with some frequency in persons who do not have BWS, it is difficult to determine whether these single cases represent a coincidental occurrence of 2 unrelated conditions or if the malignancy was indeed related to BWS.
Most commonly assoc w/positive family history of BWS
Cleft palate	Hatada et al [1997], Li et al [2001]
Omphalocele
Brain malformations involving posterior fossa	Rare
Duplications of 11p15 detectable by cytogenetic analysis ³	Developmental delay	If duplication affects KCNQ1, EKG & echocardiogram is recommended.

Molecular Mechanism

Associated Findings

Comments

Loss of methylation at IC2 (maternal)

Lower risk for tumor development overall (~3%)

Higher risk for hepatoblastoma than for WT

Hemihyperplasia may be observed.

Positive family history in those w/genomic alterations at IC2

Rare

Omphalocele

Brain malformations involving posterior fossa

Rare

Female monozygotic twinning discordant for BWS

Male monozygotic twinning is far less frequent & is assoc w/range of molecular alterations.

History of subfertility / use of ART to achieve pregnancy ¹

In parents of affected person

Gain of methylation at IC1 (maternal)

One of the highest risks for WT

Hemihyperplasia may be observed.

Positive family history in those w/deletion of IC1

Paternal UPD

One of the highest risks for WT & hepatoblastoma

More commonly assoc w/hemihyperplasia

Particularly when paternal UPD is mosaic

Severe BWS phenotype

When due to high levels of somatic mosaicism of paternal UPD

Heterozygous maternal CDKN1C pathogenic variants

Assoc w/neuroblastoma & single cases of ganglioneuroblastoma, ganglioneuroma, acute lymphocytic leukemia in children, & melanoma in an adult ²

Given that leukemia & melanoma occur with some frequency in persons who do not have BWS, it is difficult to determine whether these single cases represent a coincidental occurrence of 2 unrelated conditions or if the malignancy was indeed related to BWS.

Most commonly assoc w/positive family history of BWS

Cleft palate

Hatada et al [1997], Li et al [2001]

Omphalocele

Brain malformations involving posterior fossa

Rare

Duplications of 11p15 detectable by cytogenetic analysis ³

Developmental delay

If duplication affects KCNQ1, EKG & echocardiogram is recommended.

From: Beckwith-Wiedemann Syndrome

GeneReviews^® [Internet].

Adam MP, Feldman J, Mirzaa GM, et al., editors.

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