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Objective:To explore the clinical phenotypes, pregnancy outcomes, and follow-up of fetuses with 1q21.1 distal microdeletion/microduplication, and to provide a basis for prenatal and genetic counseling.Methods:This was a retrospective study involving 14 singleton fetuses with 1q21.1 distal microdeletion/microduplication that were prenatally diagnosed by karyotype analysis and chromosomal microarray analysis (CMA) at Wuxi Maternity and Child Health Care Hospital from January 2017 to June 2022. The results of ultrasound and genetic analysis, pregnancy outcome after genetic counseling, and postnatal follow-up were summarized using descriptive statistical methods.Results:All 14 fetuses had normal karyotypes. Out of the 14 cases, CMA indicated 1q21.1 distal microdeletion in eight cases and 1q21.1 distal microduplication in six cases. The fragments ranged from 813 kb to 4.48 Mb, all of which contained the key region of 1q21.1 microdeletion/microduplication syndrome and were pathogenic copy number variations (CNV). Among eight fetuses with distal 1q21.1 microdeletion, four cases had abnormal prenatal ultrasound findings, including one case with overlapping fingers of left hand and polyhydramnios, two were small for gestational age, and one with small head circumference. Among the six cases who underwent parental origin detection, the microdeletions were de novo in four fetuses and two fetuses were inherited from the parent with normal phenotype. As for six fetuses with distal 1q21.1 microduplication, nasal bone absence or hypoplasia was shown by ultrasound in four cases and no obvious abnormality was found in the other two cases. Parental origin detection was performed in four cases, which found that one case was de novo and the other three cases were inherited from their phenotypically normal parents. After genetic counseling, five families chose to terminate the pregnancies and the remaining nine cases continued the pregnancies to delivery. The last follow-up showed that all of the nine live births grew well, whose ages ranged from seven months to half past five years old. Conclusions:CMA is of great value in prenatal diagnosis of 1q21.1 distal microdeletion/ microduplication. Ones carrying pathogenic CNV may not develop the disease. Combined with ultrasound findings and parental genetic tracing results, individualized genetic counseling and long-term follow-up are of great importance for reasonable guidance in pregnancy outcome and reproduction.
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Objective:To explore the genetic causes of cerebellar hypoplasia (CH) diagnosed by prenatal ultrasound.Methods:This retrospective study involved 32 fetuses with CH diagnosed by prenatal ultrasound in Wuxi Maternal and Child Health Hospital from January 2014 to December 2022. Prenatal ultrasound findings and genetic testing results for amniotic fluid were collected and analyzed. The correlation between fetal CH and genetic abnormality was analyzed. A descriptive statistical method was used for data analysis.Results:(1) General data: The 32 mothers were (28.0±4.9) years old, ranging from 18 to 37 years old; the gestational age at amniocentesis was (24.2±4.0) weeks, ranging from 18 +3 weeks to 37 +2 weeks. Apart from one case lost to follow-up, the other 31 cases terminated the pregnancies, including 30 terminated before 28 weeks of gestation and one at 33 weeks of gestation due to unmarried status. (2) Ultrasonic features: Among the 32 cases, 30(93.8%) were complicated by intracranial or extracranial abnormalities including cardiac abnormalities (15 cases), dilated lateral ventricles (ten cases), and abnormalities in limbs (eight cases) and face (nine cases). Two CH cases (6.2%) were isolated. (3) Genetic testing: Among the 32 cases, 13 cases (40.6%) had normal results of amniotic fluid karyotype analysis and single nucleotide polymorphism (SNP) array. Among the 19 cases with abnormal amniotic fluid test results (59.4%), 16 cases have abnormal results in amniotic fluid karyotype analysis and SNP array detection [nine cases were numerical abnormalities, including five cases of trisomy-18, three of trisomy-21, and one of trisomy-13; seven cases were chromosomal structural abnormalities, including four cases of terminal deletion of chromosome 5 (Cri-du-Chat syndrome) and three cases of reciprocal translocation of chromosomes]. There was no abnormality in karyotype analysis of amniotic fluid in three cases. Still, their SNP array test results showed copy number variations (CNV) [one of 6q terminal deletion, one of 6q terminal deletion with 5p15.33 duplication, and one of 6q terminal deletion with 15q26.3 duplication; all variations were of unknown significance]. (4) Of the 19 cases with abnormal SNP array results, 17 were accompanied by abnormal intracranial/extracranial ultrasound findings. Among them, ten cases showed cardiac malformation, seven showed lateral ventricular widening, and seven showed limb abnormality. Conclusions:Numerical abnormalities, CDCS, and 6q terminal deletion are the most common genetic causes of CH diagnosed by prenatal ultrasound. Chromosome microarray analysis should be recommended for fetuses with ultrasound-diagnosed CH to evaluate fetal prognosis accurately.
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OBJECTIVE@#Patients with 22q11.2 microduplications have highly variable clinical phenotypes. The clinical manifestations and prognosis of 19 fetuses carrying 22q11.2 microduplications were analyzed.@*METHODS@#The fetuses were analyzed by single nucleotide polymorphism array (SNP array), which was followed by parental validation. Pregnancy outcome and clinical features of the newborns were analyzed in order to delineate genotype-phenotype correlation.@*RESULTS@#Two fetuses were identified by karyotyping analysis of amniotic fluid samples. SNP array revealed that all have carried a 468.8 kb~3.4 Mb duplication in 22q11.2 region. Two couples have refused parental verification. Seven cases were inherited from the mother, 6 were from the father, and 4 cases were de novo in origin. Three couples opted termination of the pregnancy. One fetus perished at birth. Five newborns showed delayed growth, the remaining 10 were normal.@*CONCLUSION@#The prenatal phenotype of fetuses carrying 22q11.2 microduplications are nonspecific, and the phenotypes of survivors may become more diverse along with increased age. Professional evaluation and long-term follow-up should be recommended.
Subject(s)
Female , Humans , Infant, Newborn , Pregnancy , Fetus , Genetic Counseling , Karyotyping , Phenotype , Prenatal DiagnosisABSTRACT
<p><b>OBJECTIVE</b>To explore the clinical value of screening the serum markers during the second trimester of pregnancy in preventing congenital birth defect and predicting the pregnancy outcome.</p><p><b>METHODS</b>Between November, 2011 and October, 2013, a total of 25 520 pregnant women (15-20+6 gestational weeks) underwent a screening test of triple serum markers including free beta-human chorionic gonadotrophin (free βhCG), alpha-fetoprotein (AFP), and unconjugated estriol (µE3) during the second semester of pregnancy. The women identified by the screening test as having high risks were referred to invasive prenatal diagnosis by amniocentesis, or to color Doppler ultrasound examination for suspected patent neural tube defect (NTD), and their pregnancy outcomes were followed up.</p><p><b>RESULTS</b>High-risk pregnancies were identified by the screening test in 4.91% (1254/25520) of the total cohort. Of the 818 patients receiving invasive prenatal diagnosis, the abnormal rate was 5.75% (47/818). The high-risk pregnancies identified by the screening test was associated with a significantly higher rate of abnormal outcomes compared with the low-risk pregnancies (1.91% vs 0.1%, P<0.01). Of the 210 high-risk cases of NTD, a definite diagnosis was established in 34 cases. We also found that pregnancies at an advanced age (>35 years) was associated with increased risks for trisomy 21 compared with those at younger ages (15% vs 1.65%P<0.01). The detection rate of abnormal karyotypes in pregnancies with an abnormal MoM value of a single marker was 3.17% (6/189).</p><p><b>CONCLUSION</b>Screening tests of serum markers during the second trimester of pregnancy can be helpful to identify fetal chromosomal and anatomical anomalies, predict unfavorable pregnancy outcomes, and prevent birth defects in pregnancies at an advanced age. The MoM value of a single marker in the second trimester can be indicative of potential chromosomal abnormalities.</p>