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Diagnosis and management of the phenotypic spectrum of twins with Beckwith‐Wiedemann syndrome
Author(s) -
Cohen Jennifer L.,
Duffy Kelly A.,
Sajorda Brian J.,
Hathaway Evan R.,
GonzalezGandolfi Christina X.,
RichardsYutz Jennifer,
Gunter Andrew T.,
Ganguly Arupa,
Kaplan Julie,
Deardorff Matthew A.,
Kalish Jennifer M.
Publication year - 2019
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.61164
Subject(s) - proband , pregnancy , beckwith–wiedemann syndrome , monozygotic twin , obstetrics , gestation , monochorionic twins , twin pregnancy , cohort , medicine , genetics , biology , mutation , dna methylation , gene , gene expression
Beckwith‐Wiedemann syndrome (BWS) is an overgrowth disorder with a heterogeneous phenotypic spectrum. There is an increased prevalence of monozygotic twinning in BWS. Given the epigenetic nature and phenotypic spectrum that defines BWS, twins are often discordant for clinical features, and clinicians are faced with the challenge of diagnosing and managing these twins. We present a cohort of multiple pregnancies in which one or more child from each pregnancy was diagnosed with BWS. We conducted a chart review of monochorionic and dichorionic gestations. Clinical scores for monochorionic twins demonstrated phenotypic discordance between the proband and twin. Based on linear regression analysis, a higher clinical score in the proband correlated with larger phenotypic discordance between twin siblings. Despite phenotypic discordance, however, we observed a consistent additive clinical score for a pregnancy (proband's plus twin's scores from a pregnancy). This idea of a finite degree of affectedness for a pregnancy implies a finite number of epigenetically affected cells. This further corroborates the idea that timing of monozygotic monochorionic twinning correlates with the disruption of establishment and/or maintenance of imprinting. The difference in clinical score between a proband and their twin may be due to diffused mosaicism, whereby there is an asymmetric distribution of affected cells among the multiple fetuses in a monozygotic monochorionic pregnancy, leading to a spectrum of variably affected phenotypes. Based on these findings, we recommend an algorithm for a conservative approach to clinically evaluate all children in a monozygotic multiple gestation affected by BWS.