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Xu et al. J Transl Genet Genom 2023;7:87-93 https://dx.doi.org/10.20517/jtgg.2023.10 Page 79

[10]
be involved . First, the sensitivity of adenylate cyclase activity to vasopressin gradually increases with fetal
age, making the expression of NKCC2 and NCC independent of MAGED2 beyond a certain period of renal
development. In addition, MAGED2 is required for cAMP generation and induction of the transcription
[31]
factor HIF-1α under hypoxia ; the significant increase of oxygenation after birth may promote the
synthesis of NKCC2 and NCC. Whether MAGED2 pathogenic variants interfere with the expression of
other proteins and cause extra kidney manifestations or may have some impact on female carriers is still
[11]
unknown.

The dominant presentation of our case was severe polyhydramnios, which led to the mother presenting
with premature rupture of membranes at 30 WG. However, after treatment with amnioreduction and
indomethacin, the amniotic fluid decreased since 32 WG. These dynamic changes in amniotic fluid volume
indicated polyhydramnios was not related to fetal structural abnormalities. As we were initially unaware of
antenatal BS due to its quite rare feature, biochemical analyses of amniotic fluids were not performed, which
was a limitation of our report. Prenatal genetic testing demonstrated that polyhydramnios was caused by BS
type 5, which provided evidence for timely genetic counseling and postnatal management of the patient. In
addition, our case’s postnatal mild symptoms may be associated with his gestational age at birth relatively
close to term. A French boy with antenatal BS postnatally got a genetic diagnosis by identified MAGED2 De
novo variant c.967C>T, while the detailed manifestations were not described . Our case complemented the
[11]
phenotype of MAGED2 variant c.967C>T. Besides our case, there were three cases prenatally diagnosed as
BS type 5 caused by MAGED2 splice site variant, deletion of the entire MAGED2 gene and frameshift
variant, respectively [14,15,18] . Different variant types of MAGED2, including nonsense, missense, splice site,
frameshift, and large deletion, had been reported, but fortunately, most of the patients had a favorable
outcome [10-13,15-18] . Prenatal genetic diagnosis and subsequent amnioreduction and prenatal indomethacin
therapy seem to have a beneficial effect in the fetus with BS type 5, especially on the progression of
polyhydramnios; therefore, extreme prematurity and related complications could be prevented.

In conclusion, we report a case of prenatal molecular diagnosis of BS type 5, which extends the phenotypic
spectrum. Meanwhile, we share our experience of prenatal indomethacin therapy and discuss the optimal
management approach for fetuses with BS type 5. Timely prenatal identification of BS type 5 could guide the
management of polyhydramnios and postnatal symptoms.

DECLARATIONS
Acknowledgments
We thank the participating family.

Authors’ contributions
Conception and design of the work, interpretation of the results, editing of the manuscript, and final
approval of the version to be published: Wang F
Drafting of the manuscript, data acquisition, and final approval of the version to be published: Xu K
Administrative, technical, and material support, critical revision of the manuscript, and final approval of the
version to be published: Zhang Y, Hou X, Yang H, Ding J

Availability of data and materials
All datasets generated for this study are included in the manuscript material.

Financial support and sponsorship
None.