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Objective: The recurrent 1q21.1 microdeletion syndrome is an autosomal dominant disorder and is characterized by dysmorphic facial features, microcephaly, developmental delay, and congenital defects. However, most studies on the distal deletions in the 1q21.1 region were diagnosed postnatally. This study aimed to provide a better understanding of the ultrasound and molecular findings of fetuses with recurrent 1q21.1 microdeletions in prenatal diagnosis. Methods: In this retrospective study, we reported 21 cases with the recurrent 1q21.1 microdeletion syndrome diagnosed at our prenatal diagnostic center from January 2016 to January 2023. The clinical data were reviewed for these cases, including the maternal demographics, indications for invasive testing, ultrasound findings, CMA results, and pregnancy outcomes. Results: In the study, a total of 21 cases with recurrent 1q21.1 microdeletions were diagnosed prenatally by CMA. Fifteen cases were described with ultrasound indications, and the most common findings are as follows: increased nuchal translucency (NT) (26.7%), intrauterine growth retardation (IUGR) (26.7%), congenital heart defects (CHD) (20%), and congenital anomalies of the kidney and urinary tract (CAKUT) (13.3%). All the cases with the distal 1q21.1 deletions contain the common minimal region (located between BP3 and BP4) and eight OMIM genes. Parental studies to determine the inheritance of the deletion were performed for eight cases, and half of the cases were inherited from one of the parents. Pregnancy outcomes were available for nine cases; eight (88.9%) pregnancies were determined to be terminated and one (11.1%) was fullterm delivery. Conclusion: To our knowledge, this is the largest study to find that fetuses with recurrent 1q21.1 microdeletions were closely associated with increased NT, CHD, IUGR, and CAKUT. In addition, ours is the first study to report that cerebral ventriculomegaly might be associated with recurrent 1q21.1 microdeletions. More comprehensive studies are needed for a better understanding of the prenatal phenotype-genotype relationship of the recurrent 1q21.1 microdeletion syndrome in future. [ABSTRACT FROM AUTHOR]

Umbilical Artery Thrombosis (UAT) is an extremely rare complication of pregnancy strongly associated with severe fetal distress and death. The pathogenesis is still unclear but it is often associated with anatomical cord abnormalities that leads to blood stasis and thrombosis formation. Other possible risk factors are maternal thrombophilia, autoimmune disease, gestational diabetes, hypertension disorders of pregnancy and Rh-alloimmunization. The most common clinical symptom is the reduction of fetal movements. The diagnosis is histopathological, but it can be suspected by clinical and prenatal ultrasound findings. Generally, the first choice therapy is the immediate delivery with cesarean section. This study reported a case of a spontaneous intrauterine UAT in a low-risk pregnancy and a systematic review of the literature on clinical, ultrasound and histopathological findings of UAT, in order to help clinicians in the diagnostic process and management of this rare complication. [ABSTRACT FROM AUTHOR]

Objective: Wolf–Hirschhorn syndrome (WHS) is a congenital malformation syndrome with poor prognosis. It is associated with a heterozygous deletion of chromosome 4p16.3. Adequate knowledge of prenatal phenotypes and proper prenatal counseling are essential for intrauterine diagnosis. Method: We retrospectively analyzed 11 prenatal cases of WHS diagnosed using low‐depth whole‐genome sequencing (copy number variation sequencing) performed at our hospital from May 2017 to September 2022 and reviewed their prenatal ultrasound reports in detail. We also analyzed WHS cases (including prenatal and postnatal) with abnormal prenatal ultrasound findings in the published literature over the past 20 years. Results: Among the 11 fetuses with a prenatal diagnosis of WHS in our hospital, four cases showed abnormal prenatal ultrasound findings, including shrunken kidneys, ventricular septal defect, a small stomach, fetal growth restriction (FGR), enlarged posterior fossa, and soft ultrasonic markers. Our four cases were combined with 114 published WHS cases with prenatal ultrasound abnormalities from other medical institutions. Of the 118 cases, 59.3% (70 of 118) were multiple malformations. The most frequent ultrasound features observed in all 118 cases were FGR (76.3%, 90 of 118), followed by facial anomalies (28.8%, 34 of 118), central nervous system anomalies (27.1%, 32 of 118), and soft ultrasound markers (23.7%, 28 of 118). Other less common phenotypes included cardiac anomalies (19.5%, 23 of 118), genitourinary anomalies (19.5%, 23 of 118), increased NT/NF (12.7%, 15 of 118), skeletal anomalies (11.9%, 14 of 118), a single umbilical artery (10.2%, 12 of 118), gastrointestinal anomalies (9.3%, 11 of 118), oligohydramnios (8.5%, 10 of 118), cystic hygroma (5.1%, six of 118), hydrops/pleural effusion/ascites (2.5%, three of 118), and polyhydramnios (2.5%, three of 118). Conclusion: This study improved our understanding of the prenatal presentation of WHS by analyzing prenatal ultrasound abnormalities. The timely identification of prenatal ultrasound abnormalities can provide accurate consultation for pregnant women, improve the prenatal detection of WHS, and enable early prenatal management and intervention of WHS. [ABSTRACT FROM AUTHOR]

Abstract Objective Wolf–Hirschhorn syndrome (WHS) is a congenital malformation syndrome with poor prognosis. It is associated with a heterozygous deletion of chromosome 4p16.3. Adequate knowledge of prenatal phenotypes and proper prenatal counseling are essential for intrauterine diagnosis. Method We retrospectively analyzed 11 prenatal cases of WHS diagnosed using low‐depth whole‐genome sequencing (copy number variation sequencing) performed at our hospital from May 2017 to September 2022 and reviewed their prenatal ultrasound reports in detail. We also analyzed WHS cases (including prenatal and postnatal) with abnormal prenatal ultrasound findings in the published literature over the past 20 years. Results Among the 11 fetuses with a prenatal diagnosis of WHS in our hospital, four cases showed abnormal prenatal ultrasound findings, including shrunken kidneys, ventricular septal defect, a small stomach, fetal growth restriction (FGR), enlarged posterior fossa, and soft ultrasonic markers. Our four cases were combined with 114 published WHS cases with prenatal ultrasound abnormalities from other medical institutions. Of the 118 cases, 59.3% (70 of 118) were multiple malformations. The most frequent ultrasound features observed in all 118 cases were FGR (76.3%, 90 of 118), followed by facial anomalies (28.8%, 34 of 118), central nervous system anomalies (27.1%, 32 of 118), and soft ultrasound markers (23.7%, 28 of 118). Other less common phenotypes included cardiac anomalies (19.5%, 23 of 118), genitourinary anomalies (19.5%, 23 of 118), increased NT/NF (12.7%, 15 of 118), skeletal anomalies (11.9%, 14 of 118), a single umbilical artery (10.2%, 12 of 118), gastrointestinal anomalies (9.3%, 11 of 118), oligohydramnios (8.5%, 10 of 118), cystic hygroma (5.1%, six of 118), hydrops/pleural effusion/ascites (2.5%, three of 118), and polyhydramnios (2.5%, three of 118). Conclusion This study improved our understanding of the prenatal presentation of WHS by analyzing prenatal ultrasound abnormalities. The timely identification of prenatal ultrasound abnormalities can provide accurate consultation for pregnant women, improve the prenatal detection of WHS, and enable early prenatal management and intervention of WHS.

Infectious diseases during pregnancy are still a major cause of fetal mortality and morbidity worldwide. The most common teratogenic pathogens are cytomegalovirus (CMV), varicella-zoster virus (VZV), rubeovirus, parvovirus B19, herpes simplex virus (HSV), Toxoplasma gondii, Treponema pallidum and the emergent Zika virus (ZIKV). Ultrasound findings include cerebral anomalies, orbital defects, micrognathia, cardiac defects, hepatosplenomegaly, liver calcifications, abdominal anomalies, skin and limb anomalies, edema, placental and amniotic fluid anomalies and altered Doppler analyses. The classification of ultrasound markers of congenital infections by anatomical region is reported to guide differential diagnosis and prenatal care.

• 16p11.2 CNVs were identified in 0.35% (30/8578) of prenatal SNP array results. • 16p11.2 CNVs have variable prenatal phenotypic features. • 16p11.2 CNVs are frequently inherited from parents with a milder or normal phenotype. • Vertebral deformities were frequent in cases of 16p11.2 proximal deletion. The 16p11.2 copy number variations (CNVs) are increasingly recognized as one of the most frequent genomic disorders, with a broad spectrum of phenotypes. The fetal phenotype associated with 16p11.2 CNVs is poorly described. The current study presents prenatal series of 16p11.2 CNVs and provides a better understanding of this submicroscopic imbalance in prenatal diagnosis. Retrospective case series were extracted from a single tertiary referral center performing prenatal single nucleotide polymorphism (SNP) array from April 2017 to December 2021. The maternal demographics, indication for amniocentesis, ultrasound findings, SNP array results, inheritance of the CNVs, and pregnancy outcomes were studied. We indentified 30 fetuses carrying 16p11.2 CNVs, representing 0.35% (30/8578) of prenatal SNP array results. The series included 17 fetuses with a proximal deletion, 7 with a distal deletion, 4 with a proximal duplication, and 2 with a distal duplication. Prenatal ultrasound anomalies were reported in 80% of these cases. The most common presentation was vertebral anomalies (9/30). Other features noted in more than one fetus were increased nuchal translucency/nuchal fold (NT/NF) (5/30), absent/hypoplastic nasal bone (3/30), polyhydramnios (3/30), ventricular septal defect (VSD) (2/30), unilateral mild ventriculomegaly (2/30), fetal growth restriction (FGR) (2/30), right aortic arch (2/30). All the 9 vertebral anomalies were present in fetuses harboring proximal deletion (9/17). Familial transmission was confirmed in 44% of cases (11/25) and termination of pregnancy was requested in 62.1% (18/29) of cases. The 16p11.2 CNVs can have variable prenatal phenotypes and these CNVs are frequently inherited from parents with a milder or normal phenotype. Our results underline that vertebral deformities were frequent in cases of 16p11.2 proximal deletion, and further demonstrate the incomplete penetrance of the CNVs. [ABSTRACT FROM AUTHOR]

Background: The incidence of syphilis among Canadian women of childbearing age has risen dramatically in the past decade, with a resurgence of infants born with congenital syphilis. While guidelines exist to guide maternal infection during pregnancy, there is little evidence available to guide management in situations where the developing fetus is found to be severely affected. Case review: Our patient presented in the second trimester of her pregnancy as syphilis contact. Positive serologic tests (venereal disease research laboratory titre of 1:64) and a chancre suggested primary infection. Ultrasound demonstrated a fetus at 19+3 weeks gestation with hydrops fetalis and a markedly abnormal brain. Amniocentesis confirmed congenital syphilis infection on polymerase chain reaction testing. After nine days of intravenous penicillin G, the fetal status had worsened, and the family ultimately chose a medical termination of the pregnancy. Discussion: Evolving ultrasound technology has allowed us to identify severely affected fetuses, who may historically have been delivered stillborn. Following routine syphiliotherapy with benzathine penicillin, these abnormal ultrasound features may take weeks or months to reverse, which poses a challenge in prognostication and counselling. Case reports data suggests intensive treatment with intravenous penicillin may be effective in severe cases where fetal hydrops is present. Conclusion: This case highlights the potential morbidity of fetal syphilis infection and underscores the paucity of current literature. Information sharing will be essential to build a modern knowledge base on treating this ancient disease.

Infectious diseases during pregnancy are still a major cause of fetal mortality and morbidity worldwide. The most common teratogenic pathogens are cytomegalovirus (CMV), varicella-zoster virus (VZV), rubeovirus, parvovirus B19, herpes simplex virus (HSV), Toxoplasma gondii, Treponema pallidum and the emergent Zika virus (ZIKV). Ultrasound findings include cerebral anomalies, orbital defects, micrognathia, cardiac defects, hepatosplenomegaly, liver calcifications, abdominal anomalies, skin and limb anomalies, edema, placental and amniotic fluid anomalies and altered Doppler analyses. The classification of ultrasound markers of congenital infections by anatomical region is reported to guide differential diagnosis and prenatal care. [ABSTRACT FROM AUTHOR]

Neu–Laxova syndrome is a rare and lethal genetic disease with autosomal recessive inheritance involving abnormalities of multiple systems. It was first reported in 1971. Since then, just eighty-eight cases have been reported. The syndrome is characterized by early and severe growth restriction, and craniofacial anomalies, such as microcephaly, hypertelorism and other malformations, resulting in quite characteristic features. Additionally, it might appear as generalized edema, flexion contractures and other malformations of the extremities, abnormalities in the CNS (central nervous system), skin (severe ichthyosis), and genitourinary and cardiac abnormalities. We present the case of a patient who had her first pregnancy with a fetus with Neu–Laxova syndrome diagnosed in our center during the second-trimester ultrasound. The ultrasound findings suggested the diagnosis, which was confirmed with a genetic study of the amniotic fluid: the variant of the PSAT1 gene, associated with NLS (Neu–Laxova syndrome) 2 in homozygosis. Moreover, there was a second pregnancy with a fetus carrying the same mutation in heterozygosis. In addition, we have carried out a review of published literature about this disease up to the present time. [ABSTRACT FROM AUTHOR]

Background: The incidence of syphilis among Canadian women of childbearing age has risen dramatically in the past decade, with a resurgence of infants born with congenital syphilis. While guidelines exist to guide maternal infection during pregnancy, there is little evidence available to guide management in situations where the developing fetus is found to be severely affected.Case review: Our patient presented in the second trimester of her pregnancy as syphilis contact. Positive serologic tests (venereal disease research laboratory titre of 1:64) and a chancre suggested primary infection. Ultrasound demonstrated a fetus at 19+3 weeks gestation with hydrops fetalis and a markedly abnormal brain. Amniocentesis confirmed congenital syphilis infection on polymerase chain reaction testing. After nine days of intravenous penicillin G, the fetal status had worsened, and the family ultimately chose a medical termination of the pregnancy.Discussion: Evolving ultrasound technology has allowed us to identify severely affected fetuses, who may historically have been delivered stillborn. Following routine syphiliotherapy with benzathine penicillin, these abnormal ultrasound features may take weeks or months to reverse, which poses a challenge in prognostication and counselling. Case reports data suggests intensive treatment with intravenous penicillin may be effective in severe cases where fetal hydrops is present.Conclusion: This case highlights the potential morbidity of fetal syphilis infection and underscores the paucity of current literature. Information sharing will be essential to build a modern knowledge base on treating this ancient disease. [ABSTRACT FROM AUTHOR]

Objective: The recurrent 1q21.1 microdeletion syndrome is an autosomal dominant disorder and is characterized by dysmorphic facial features, microcephaly, developmental delay, and congenital defects. However, most studies on the distal deletions in the 1q21.1 region were diagnosed postnatally. This study aimed to provide a better understanding of the ultrasound and molecular findings of fetuses with recurrent 1q21.1 microdeletions in prenatal diagnosis., Methods: In this retrospective study, we reported 21 cases with the recurrent 1q21.1 microdeletion syndrome diagnosed at our prenatal diagnostic center from January 2016 to January 2023. The clinical data were reviewed for these cases, including the maternal demographics, indications for invasive testing, ultrasound findings, CMA results, and pregnancy outcomes., Results: In the study, a total of 21 cases with recurrent 1q21.1 microdeletions were diagnosed prenatally by CMA. Fifteen cases were described with ultrasound indications, and the most common findings are as follows: increased nuchal translucency (NT) (26.7%), intrauterine growth retardation (IUGR) (26.7%), congenital heart defects (CHD) (20%), and congenital anomalies of the kidney and urinary tract (CAKUT) (13.3%). All the cases with the distal 1q21.1 deletions contain the common minimal region (located between BP3 and BP4) and eight OMIM genes. Parental studies to determine the inheritance of the deletion were performed for eight cases, and half of the cases were inherited from one of the parents. Pregnancy outcomes were available for nine cases; eight (88.9%) pregnancies were determined to be terminated and one (11.1%) was full-term delivery., Conclusion: To our knowledge, this is the largest study to find that fetuses with recurrent 1q21.1 microdeletions were closely associated with increased NT, CHD, IUGR, and CAKUT. In addition, ours is the first study to report that cerebral ventriculomegaly might be associated with recurrent 1q21.1 microdeletions. More comprehensive studies are needed for a better understanding of the prenatal phenotype-genotype relationship of the recurrent 1q21.1 microdeletion syndrome in future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Lei, Guo, Ma, Zhen, Zhang and Li.)

Neu–Laxova syndrome is a rare and lethal genetic disease with autosomal recessive inheritance involving abnormalities of multiple systems. It was first reported in 1971. Since then, just eighty-eight cases have been reported. The syndrome is characterized by early and severe growth restriction, and craniofacial anomalies, such as microcephaly, hypertelorism and other malformations, resulting in quite characteristic features. Additionally, it might appear as generalized edema, flexion contractures and other malformations of the extremities, abnormalities in the CNS (central nervous system), skin (severe ichthyosis), and genitourinary and cardiac abnormalities. We present the case of a patient who had her first pregnancy with a fetus with Neu–Laxova syndrome diagnosed in our center during the second-trimester ultrasound. The ultrasound findings suggested the diagnosis, which was confirmed with a genetic study of the amniotic fluid: the variant of the PSAT1 gene, associated with NLS (Neu–Laxova syndrome) 2 in homozygosis. Moreover, there was a second pregnancy with a fetus carrying the same mutation in heterozygosis. In addition, we have carried out a review of published literature about this disease up to the present time.