Two Consecutive Pregnancies with Simpson-Golabi-Behmel Syndrome Type 1: Case Report and Review of Published Prenatal Cases

Abstract

Fetal overgrowth and numerous congenital malformations can be detected in every trimester of pregnancy. New technologies in molecular testing, such as chromosomal microarray analysis and next-generation sequencing, continually demonstrate advantages for definitive diagnosis in fetal life. Simpson-Golabi-Behmel (SGB) syndrome is a rare but well-known overgrowth condition that is rarely diagnosed in the prenatal setting. We report 3 cases of SGB syndrome in 2 consecutive pregnancies. In our series, distinctive prenatal sonographic findings led to molecular diagnosis. Exome sequencing from fetal DNA revealed a hemizygous splice site variant in the GPC3 gene: NM_004484.3:c.1166+ 1G>T. The mother is a heterozygous carrier. We also provide an overview of the previously published 57 prenatal cases of SGB syndrome with prevalence estimation of the symptoms to aid prenatal differential diagnosis of fetal overgrowth syndromes.

Prenatal case of Simpson–Golabi–Behmel syndrome with a de novo 370Kb‐sized microdeletion of Xq26.2 compassing partial GPC3 gene and review

“…The differential diagnosis of SGBS includes conditions presenting with craniofacial dysmorphology and fetal macrosomia, such as Beckwith‐Wiedemann syndrome (BWS) (OMIM 130650), Sotos syndrome (OMIM 117550), Weaver syndrome (OMIM 277590), Perlman syndrome (OMIM 267000) or Pallister‐Killian syndrome (PKS; OMIM 601803). The main overlap in clinical presentations in the prenatal setting for SGBS would be with BWS (Ridnoi et al, 2018). Therefore, it is still challenging to make a definite diagnosis for prenatal SGBS just based on the limited information from ultrasound imaging.…”

“…Although NT is a well‐known soft marker of chromosomal anomalies, enlarged NT may also present in many monogenic defect syndromes, such as Noonan syndrome (Pergament et al, 2011). According to some previous prenatal reports on SGBS, elevated maternal serum alpha‐fetoprotein (MSAFP) levels, increased NT or thickened NF were also suggested as antenatal markers for SGBS (Chen et al, 1993; Li & McDonald, 2009; Ridnoi et al, 2018; Young et al, 2006). In another review for prenatal symptoms of SGBS1, it was described that fetal macrosomia accounted for 86% of the cases, polyhydramnios was reported in 70% of cases, and organomegaly was found in 60% of cases (Ridnoi et al, 2018).…”

“…According to some previous prenatal reports on SGBS, elevated maternal serum alpha‐fetoprotein (MSAFP) levels, increased NT or thickened NF were also suggested as antenatal markers for SGBS (Chen et al, 1993; Li & McDonald, 2009; Ridnoi et al, 2018; Young et al, 2006). In another review for prenatal symptoms of SGBS1, it was described that fetal macrosomia accounted for 86% of the cases, polyhydramnios was reported in 70% of cases, and organomegaly was found in 60% of cases (Ridnoi et al, 2018). At 21 weeks of gestation, our case also manifested with macrosomia, polyhydramnios, organomegaly, facial clefts, and congenital heart defects.…”

Identification of Novel Key Biomarkers in Simpson-Golabi-Behmel Syndrome (SGBS): Evidence from Bioinformatics Analysis

“…[13] Different mutations have been described in SGBS type one. [14][15][16][17][18][19][20][21][22] Overgrowth Syndrome caused by mutations in glypican 3 (GPC3) gene is localized on Xq26.1 [23,24] which encrypts glypican-3. [17,19,20,[25][26][27][28][29] that seemingly acting a bad part in growth control by an anonymous fate, However, outcomes from an exhaustive qualified study of growth forms in dual mutants missing GPC3 provided conclusive genetic evidence inconsistent with the theory that GPC3 performances as a growth suppressor.…”

Identification of novel key biomarkers in Simpson-Golabi-Behmel Syndrome: Evidence from bioinformatics analysis

“…[13] Different mutations have been reported in SGBS type I. [14][15][16][17][18][19][20][21][22] This dysplasia syndrome caused by loss-of-function mutations of the X-linked GPC3 gene is localized on Xq26.1 [23,24] which encodes a developmentally regulated cell membrane proteoglycan, glypican-3. [17,19,20,[25][26][27][28][29] that apparently plays a negative role in growth control by an unknown mechanism, However, outcomes from a detailed comparative analysis of growth patterns in dual mutants lacking GPC3 provided conclusive genetic evidence inconsistent with the theory that GPC3 performances as a growth suppressor by downregulating an IGF ligand.…”