OBJECTIVE: To explore the clinical phenotype, pregnancy outcome and follow-up of fetuses with 15q11.2BP1-BP2 microdeletions in order to provide a basis for prenatal and reproductive consultation. METHODS: From March 2019 to December 2023, 20 fetuses who were diagnosed with 15q11.2BP1-BP2 microdeletion syndrome at the Prenatal Diagnosis Center of General Hospital of Ningxia Medical University were selected as the study subjects. Results of genetic testing and ultrasound examination, outcome of pregnancy, and postnatal follow-up were retrospectively analyzed. This study has been approved by the Ethics Committee of General Hospital of Ningxia Medical University ([2020]0520B). RESULTS: None of the 20 fetuses was found to have chromosomal abnormality, whilst all were found to harbor a 15q11.2 BP1-BP2 microdeletion by low-depth whole genome sequencing (CNV-seq). The range of deletions was determined as 0.26 ~ 0.87 Mb, and all were rated as pathogenic CNVs. Three fetuses had abnormal ultrasound findings, including 1 with widened renal pelvis, 1 with agenesis of corpus callosum, and 1 with nuchal fold thickening. Parental verification in 10 couples verified that two fetal deletions were de novo, whilst the remaining eight were inherited from a phenotypically normal parent. Following genetic counseling, three couples had opted to terminate the pregnancy, whilst the remaining 17 had continued with the pregnancy until delivery. The 17 liveborns were followed up for 2 months to 5 years, with no obvious abnormality in growth and development noted. CONCLUSION CNV-seq plays an important role in the prenatal diagnosis of 15q11.2 BP1-BP2 microdeletions. Such deletions may not always lead to disease phenotypes. Individualized consultation and long-term follow-up, in combination with intrauterine ultrasound and parental verification are necessary.
Humans ; Female ; Pregnancy ; Chromosomes, Human, Pair 15/genetics* ; Genetic Counseling ; Prenatal Diagnosis ; Chromosome Deletion ; Adult ; Fetus/abnormalities* ; Retrospective Studies ; Pregnancy Outcome ; Ultrasonography, Prenatal ; Genetic Testing ; DiGeorge Syndrome/diagnosis* ; Male

OBJECTIVE: To carry out genetic testing on two fetuses with prenatal ultrasound finding of polydactyly and renal abnormalities to determine the underlying causes. METHODS: Two fetuses with structural abnormalities detected by prenatal ultrasound at Cangzhou People's Hospital in 2021 were selected as the study subjects. Genomic DNA was extracted from the muscle tissue of the abortus and peripheral blood samples from both parents. Whole-exome sequencing (WES) was conducted on the trio to detect the genetic variants. Quantitative PCR was used to validate the exonic deletions. This study has been approved by the Ethics Committee of Cangzhou People's Hospital (Ethics No.K2020-049). RESULTS: Prenatal ultrasound revealed postaxial polydactylies of fingers and toes and slightly enlarged kidneys with increased echogenicity in fetus 1, along with polydactyly of both hands, enlarged kidneys, and enhanced echogenicity of renal parenchyma in fetus 2. Trio-WES analysis revealed that fetus 1 has harbored a pathogenic c.1339G>A variant of the BBS1 gene, along with a heterozygous 426 bp deletion in the 11q13.2 region, which was unreported previously. The deletion has involved exons 10 and 11 of the BBS1 gene. The two variants were inherited from its mother and father, respectively. Fetus 2 was found to harbor a pathogenic c.539G>A variant and a likely pathogenic c.49G>A variant of the BBS10 gene, which were inherited from its mother and father, respectively. The c.49G>A variant has not been documented in databases and the literature. CONCLUSION Two rare fetuses with Bardet-Biedl syndrome have been diagnosed. Above finding has expanded the mutational spectrum of this syndrome and has important implications for genetic counseling for the affected families.
Humans ; Bardet-Biedl Syndrome/diagnostic imaging* ; Female ; Pregnancy ; Fetus/abnormalities* ; Ultrasonography, Prenatal ; Phenotype ; Polydactyly/diagnostic imaging* ; Exome Sequencing ; Adult ; Genetic Testing ; Male ; Prenatal Diagnosis ; Group II Chaperonins/genetics* ; Microtubule-Associated Proteins

OBJECTIVE: To explore the clinical and genetic characteristics of fetuses with Kabuki syndrome (KS) and their genotype-phenotype correlation. METHODS: A retrospective analysis was carried out on the prenatal manifestations and results of genetic testing of six KS fetuses diagnosed by whole-exome sequencing (WES). The findings were compared with 28 prenatally diagnosed KS cases reported in the literature to summarize the prenatal features of KS. This study has been approved by the Ethics Committee of Maternal and Child Health Care Hospital of Hubei Province (Ethics No.: 2025-141-01). RESULTS: Prenatal ultrasound findings in KS fetuses showed high heterogeneity. The most common abnormalities were cardiac (23/35, 65.7%) and renal (20/35, 57.1%), which are often accompanied by amniotic fluid abnormalities (5/35, 14.3%), single umbilical artery (5/35, 14.3%), and fetal hydrops (4/35, 11.4%). Among the six fetuses from our center, all were identified by WES to harbor pathogenic variants of the KMT2D gene, and all of which were de novo. These included 3 frameshift variants, 2 nonsense variant, and 1 missense variant, among which 4 were unreported previously. CONCLUSION This study has expanded the mutational spectrum of the KMT2D gene. Prenatal ultrasound findings of KS lack specificity, though multi-system anomalies or specific soft markers may indicate KS. WES is an effective tool for the diagnosis, and KS should be included in the differential diagnosis list for prenatal cardiac and renal abnormalities.
Humans ; Hematologic Diseases/diagnostic imaging* ; Face/diagnostic imaging* ; Female ; Vestibular Diseases/diagnostic imaging* ; Abnormalities, Multiple/diagnostic imaging* ; Pregnancy ; Ultrasonography, Prenatal ; Adult ; Neoplasm Proteins/genetics* ; Retrospective Studies ; DNA-Binding Proteins/genetics* ; Male ; Exome Sequencing ; Fetus/diagnostic imaging* ; Genetic Association Studies ; Mutation

OBJECTIVE: To explore the detection rate of copy number variations (CNVs) in fetuses with isolated Congenital anomalies of the kidney and urinary tract (CAKUT) and pregnancy outcomes in order to provide a basis for genetic counseling. METHODS: One hundred and eighty eight fetuses who underwent chromosomal microarray analysis (CMA) due to isolated CAKUT detected by prenatal ultrasonography at Qingdao Women and Children's Hospital from January 2021 to December 2024 were selected as the study subjects. According to the ultrasound findings, the fetuses were divided into 8 groups, including renal parenchymal dysplasia group, renal cystic dysplasia group, simple renal parenchymal echo enhancement group, abnormal development of renal collecting system group, duplicated kidney group, ectopic kidney group, horseshoe kidney group, and bladder/posterior urethral abnormalities group. The detection of CNVs was retrospectively analyzed, and the pregnant women were followed up to summarize their pregnancy outcomes. 2 test (or Fisher's exact probability method) was used to compare the CNV detection rates between the groups. This study was approved by the Medical Ethics Committee of the Qingdao Women and Children's Hospital (Ethics No.: QFELL-YJ-2025-85). RESULTS: Among the 188 fetuses with isolated CAKUT, 23 CNVs (12.23%) were detected, of which 13 cases (6.91%) were pathogenic and 10 cases were rated as variants of unknown significance (VOUS). Among the 8 groups, the three groups with the highest proportion were renal cystic dysplasia group, renal metaplasia group, and renal parenchymal dysplasia group. The detection rates of pathogenic CNVs in the three groups were 1.79% (1/56), 6.78% (4/59), and 16.67% (5/30), respectively, with statistically significant differences (P < 0.05). Parental verification was conducted on 12 fetuses detected with the CNVs, confirming that 2 cases were de novo and 10 were inherited from parents with a normal phenotype. After genetic counseling, the parents of 9 fetuses opted to terminate the pregnancy, while 11 chose to continue with the pregnancy, and 3 were lost to follow-up. At the time of last follow-up, the youngest offspring was 5 months old and the oldest was 3 years and 11 months old. One child had renal aplasia, and two were born with hydronephrosis, which have been cured through surgery. The remainders had no obvious abnormality with their growth and development. CONCLUSION CMA testing has important value for prenatal diagnosis of isolated CAKUT. In this study, the detection rate of pathogenic CNVs has increased sequentially in fetuses with renal cystic developmental abnormalities, renal collecting system developmental abnormalities, and renal parenchymal dysplasia, while there was no significant difference in the detection rate of CNVs. For fetuses with isolated CAKUT detected by prenatal ultrasound, CMA testing should be considered, and reasonable pregnancy decisions should be made based on the results of prenatal ultrasound and parental verification.
Humans ; Female ; Pregnancy ; Prenatal Diagnosis/methods* ; DNA Copy Number Variations/genetics* ; Kidney/abnormalities* ; Adult ; Ultrasonography, Prenatal ; Urogenital Abnormalities/diagnosis* ; Microarray Analysis/methods* ; Retrospective Studies ; Urinary Tract/abnormalities* ; Fetus ; Pregnancy Outcome ; Vesico-Ureteral Reflux

OBJECTIVE: To explore the prenatal features and genetic etiology of a fetus with Short-rib cage dysplasia (SRTD) due to variants of DYNC2H1 gene. METHODS: A pregnant women presented at Xinxiang Central Hospital in June 2020 for abnormal prenatal ultrasound findings was selected as the study subject. With informed consent obtained, amniotic fluid sample was extracted from the woman, and clinical data of the fetus were collected. Whole exome sequencing (WES) was carried out, and candidate variants were verified by Sanger sequencing. This study was approved by the Medical Ethics Committee of Xinxiang Central Hospital [Ethics No.: 2025-214-01(K)]. RESULTS: At 25⁺⁶ weeks gestation, genetic testing revealed that the fetus has harbored compound heterozygous variants of the DYNC2H1 gene, namely c.10585C>T (p.Arg3529Ter) and c.8954T>G (p.Val2985Gly), which were derived from its father and mother, respectively. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.10585C>T (p.Arg3529Ter) and c.8954T>G (p.Val2985Gly) variants were classified as pathogenic (PVS1+PM2_supporting+PM3+PP5) and likely pathogenic (PM1+PM2_supporting+PM3+PP3), respectively. Bioinformatics analysis suggested that both variants may affect the 3D structure of the DYNC2H1 protein. CONCLUSION The compound heterozygous variants of c.10585C>T (p.Arg3529Ter) and c.8954T>G (p.Val2985Gly) of the DYNC2H1 gene probably underlay the pathogenesis of SRTD in the fetus. Above findings had facilitated prenatal diagnosis and genetic counseling for the couple.
Humans ; Female ; Pregnancy ; Cytoplasmic Dyneins/chemistry* ; Prenatal Diagnosis ; Adult ; Short Rib-Polydactyly Syndrome/diagnostic imaging* ; Mutation ; Exome Sequencing ; Fetus/abnormalities* ; Ultrasonography, Prenatal

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) for the diagnosis of fetuses with anomalies of the central nervous system (CNS) and summarize the outcome of the pregnancies and follow-up. METHODS: A total of 636 fetuses from June 2014 to December 2020 who were referred to the Prenatal Diagnosis Center of Nanjing Drum Tower Hospital due to abnormal CNS prompted by ultrasound were selected as the research subjects. Based on the ultrasound findings, the fetuses were divided into ventricular dilatation group (n = 441), choroid plexus cyst group (n = 41), enlarged posterior fossa group (n = 42), holoprosencephaly group (n = 15), corpus callosum hypoplasia group (n = 22), and other anomaly group (n = 75). Meanwhile, they were also divided into isolated (n = 504) and non-isolated (n = 132) groups based on the presence of additional abnormalities. Prenatal samples (amniotic fluid/chorionic villi/umbilical cord blood) or abortus tissue were collected for the extraction of genomic DNA and CMA assay. Outcome of the pregnancies and postnatal follow-up were summarized and subjected to statistical analysis. RESULTS: In total 636 fetuses with CNS anomalies (including 89 abortus tissues) were included, and 547 cases were followed up. The overall detection rate of CMA was 11.48% (73/636). The detection rates for the holoprosencephaly group, ACC group, choroid plexus cyst group, enlarged posterior fossa group, ventricular dilatation group and other anomaly group were 80% (12/15), 31.82% (7/22), 19.51% (8/41), 14.29% (6/42), 7.48% (33/441) and 9.33% (7/75), respectively. Compared with the isolated CNS anomaly group, the detection rate for the non-isolated CNS anomaly group was significantly higher (6.35% vs. 31.06%) (32/504 vs. 41/132) (χ² = 62.867, P < 0.001). Follow up showed that, for 52 fetuses with abnormal CMA results, 51 couples have opted induced labor, whilst 1 was delivered at full term with normal growth and development. Of the 434 fetuses with normal CMA results, 377 were delivered at full term (6 had developmental delay), and 57 couples had opted induced labor. The rate of adverse pregnancy outcome for non-isolated CNS abnormal fetuses was significantly higher than that of isolated CNS abnormal fetuses (26.56% vs. 10.54%) (17/64 vs. 39/370) (χ² = 12.463, P < 0.001). CONCLUSION Fetuses with CNS anomaly should be tested with CMA to determine the genetic cause. Most fetuses with negative CMA result have a good prognosis, but there is still a possibility for a abnormal neurological phenotype. Fetuses with CNS abnormalities in conjunct with other structural abnormalities are at increased risk for adverse pregnancy outcomes.
Female ; Pregnancy ; Humans ; Holoprosencephaly ; Prenatal Diagnosis/methods* ; Central Nervous System ; Fetus/abnormalities* ; Nervous System Malformations/genetics* ; Microarray Analysis ; Central Nervous System Diseases ; Cysts ; Chromosome Aberrations ; Ultrasonography, Prenatal/methods*

OBJECTIVE: To explore the genetic basis for a fetus with multiple malformations. METHODS: Clinical data of the fetus was collected, Amniotic fluid sample of the fetus was subjected to conventional G-banded karyotyping, low-depth whole genome copy number variants detection and whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing of the fetus and its parents. RESULTS: Prenatal ultrasound scan at 21⁺⁵ gestational weeks had revealed increased nuchal thickness (9.0 mm), enhanced echos of bilateral renal parenchyma, seroperitoneum, left pleural effusion and right displacement of the heart. The mother had a previous history of terminated pregnancy for multiple fetal anomalies. No abnormality was found by conventional karyotyping and CNV analysis, though WES revealed that the fetus has harbored a de novo heterozygous c.607C>T (p.Arg203Trp) variant of the ACS1 gene (NM_018026.3), and the result was validated by Sanger sequencing. CONCLUSION Through WES and prenatal ultrasonography, the fetus was diagnosed with Schuurs-Hoeijmakers syndrome due to the heterozygous c.607C>T (p.Arg203Trp) variant of the PACS1 gene (NM_018026.3). For fetuses with multiple malformations, WES can help to reveal the genetic etiology when CNV result is negative.
Female ; Pregnancy ; Humans ; Prenatal Diagnosis ; Ultrasonography, Prenatal ; Syndrome ; Fetus ; Abnormalities, Multiple ; Vesicular Transport Proteins

Herlyn-Werner-Wunderlich (HWW) syndrome is a rare congenital anomaly of the genitourinary tract comprising uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. Patients with HWW syndrome usually present symptoms such as dysmenorrhea, abdominal pain, pelvic mass, and purulent vaginal discharge. If not treated at an appropriate time, complications such as infertility, endometriosis, pyosalpinx, and subsequent pelvic adhesions may occur. Here, we report a case of HWW syndrome in a 7-year-old-girl who was also diagnosed as having central precocious puberty. She was brought to the pediatric department with chief complaints of lump in her breast and vaginal discharge. When she was around 2 months old, she was confirmed to have a single kidney on ultrasonography. We checked her past medical history and diagnosed her as having HWW syndrome based on the results of imaging studies, including abdominal ultrasonography and pelvic magnetic resonance imaging. She underwent treatment with gonadotropin-releasing hormone analogue for 2 years. During 24 months of follow-up, she showed no serious problems or complications. If renal anomalies are identified immediately after birth or in infancy, further screening tests should be conducted prior to menstruation for determining congenital abnormalities of the reproductive tract and vice versa.
Abdominal Pain ; Breast ; Congenital Abnormalities ; Dysmenorrhea ; Endometriosis ; Female ; Follow-Up Studies ; Gonadotropin-Releasing Hormone ; Humans ; Infertility ; Kidney ; Magnetic Resonance Imaging ; Mass Screening ; Menstruation ; Parturition ; Puberty, Precocious ; Ultrasonography ; Uterus ; Vaginal Discharge

Craniofacial abnormalities are common. It is important to examine the fetal face and skull Epub ahead of print during prenatal ultrasound examinations because abnormalities of these structures may indicate the presence of other, more subtle anomalies, syndromes, chromosomal abnormalities, or even rarer conditions, such as infections or metabolic disorders. The prenatal diagnosis of craniofacial abnormalities remains difficult, especially in the first trimester. A systematic approach to the fetal skull and face can increase the detection rate. When an abnormality is found, it is important to perform a detailed scan to determine its severity and search for additional abnormalities. The use of 3-/4-dimensional ultrasound may be useful in the assessment of cleft palate and craniosynostosis. Fetal magnetic resonance imaging can facilitate the evaluation of the palate, micrognathia, cranial sutures, brain, and other fetal structures. Invasive prenatal diagnostic techniques are indicated to exclude chromosomal abnormalities. Molecular analysis for some syndromes is feasible if the family history is suggestive.
Brain ; Chromosome Aberrations ; Cleft Palate ; Cranial Sutures ; Craniofacial Abnormalities* ; Craniosynostoses ; Female ; Fetus ; Humans ; Magnetic Resonance Imaging ; Micrognathism ; Palate ; Pregnancy ; Pregnancy Trimester, First ; Prenatal Diagnosis ; Skull ; Ultrasonography ; Ultrasonography, Prenatal*

OBJECTIVE: To analyze the application of three-dimensional power Doppler sonography (3-DPDS) in evaluation of the superior mesenteric artery (SMA) and superior mesenteric vein (SMV) in second-trimester fetus. METHODS: Three-dimensional volume probe was used to collect the 3-DPDS blood flow images in 50 normal fetuses of 22-24 weeks and 50 fetuses of 30-32 weeks, respectively. The characteristics of three-dimensional ultrasound were analyzed. The clinical and imaging data of 4 fetuses of 26-32 weeks with midgut volvulus were analyzed retrospectively. RESULTS: The display rates of SMA and SMV were 93%in normal group by 3-DPDS and those in volvulus group were 4/4 and 3/4, respectively. The SMV trunk was parallel to and on the right side of the SMA in the normal group, while 3 cases in volvulus group showed the characteristic relationship of SMV swirling around SMA. CONCLUSIONS 3-DPDS can be used to observe the spatial relationship of SMA and SMV visually in fetus during the second trimester and is of value to diagnose and predict the outcome of midgut volvulus.
Digestive System Abnormalities ; diagnostic imaging ; Female ; Fetus ; Humans ; Intestinal Volvulus ; diagnostic imaging ; Mesenteric Artery, Superior ; diagnostic imaging ; Pregnancy ; Pregnancy Trimester, Second ; Retrospective Studies ; Ultrasonography, Doppler ; standards