OBJECTIVE: To explore the prenatal and postnatal phenotypes of 22q11.2 microdeletion syndrome (22q11.2DS) and enhance clinical understanding of this condition. METHODS: Data were collected from 86 fetuses diagnosed with 22q11.2DS at four prenatal diagnostic centers across China between January 2014 and August 2025. Prenatal imaging findings, pregnancy outcomes, and postnatal conditions were analyzed. RESULTS: Among the 86 fetuses, complete ultrasound data were available for 65 cases. Cardiovascular abnormalities were observed in 42 cases, thymic hypoplasia or aplasia in 7 cases, urinary system anomalies in 6 cases, nuchal translucency (NT) thickening in 7 cases, butterfly vertebrae, clubfoot, omphalocele and diaphragmatic hernia in 1 case each, cleft lip and palate in 2 cases, and ultrasound soft markers in 13 cases. The parents of 9 fetuses opted to continue with the pregnancy. Among these, 6 showed no significant ultrasound abnormalities and no related phenotypes postnatally, while the remaining 3 exhibited ultrasound anomalies with postnatal manifestations including developmental delay, immunodeficiency, and cardiac defects. CONCLUSION Fetuses with 22q11.2DS may exhibit various ultrasound abnormalities in multiple systems before and after birth. In addition to cardiovascular anomalies, they may also present with thymic hypoplasia or aplasia, thickened NT, and urinary abnormalities. Fetuses with thickened NT or thymic anomalies should be closely monitored, and thymic assessment should be included in routine prenatal imaging evaluations. For fetuses with 22q11.2DS who show no ultrasound abnormalities, the risk of developing severe phenotypes after birth is relatively low, but occult palate clefts and psychiatric disorders cannot be ruled out. Due to limitations in sample size and follow-up duration, above conclusions require further validation through large-scale prospective studies.
Humans ; Female ; Pregnancy ; Ultrasonography, Prenatal ; DiGeorge Syndrome/genetics* ; Adult ; Male ; Follow-Up Studies ; Fetus/diagnostic imaging* ; Phenotype ; Infant, Newborn

OBJECTIVE: To explore the genetic etiology for a pregnant woman with a history of multiple adverse pregnancies and assess the phenotype-genotype correlation of 22q11.2 microduplication syndrome in her family. METHODS: Amniotic fluid sample was taken from a pregnant woman for whom non-invasive prenatal screening indicated chromosome 22 abnormalities in the fetus. Peripheral blood samples from the woman, her brother and parents were collected for high-throughput low-depth whole genome sequencing (CNV-seq). A pedigree traceability analysis of the results was conducted in conjunction with analysis of clinical manifestation. Relevant literature (from establishment to March 2025) was systematically searched. This study was approved by the Medical Ethics Committee of Mianyang Maternal and Child Health Care Hospital (Ethics No.: Lun Shen [2024]009). RESULTS: CNV-seq revealed that the fetus had harbored a 6.02 Mb duplication at 22q11.21q11.23. Karyotyping confirmed it as 46,X?dup(22)(q11.2). Pedigree verification demonstrated that the pregnant woman, her brother and mother had all carried the same duplication. Phenotypic analysis of the affected family members showed classic features of 22q11.2 microduplication syndrome, including hypernasal speech, low nasal bridge, congenital heart disease, and cognitive impairment. A total of 44 cases with full information (including three patients from this pedigree) were included in the analysis. The penetrance of 22q11.2 duplication was approximately 29.5% (13/44), and 52.3% (23/44) of the cases had inherited the variant from a phenotypically normal parent. CONCLUSION This study has identified the genetic basis for the woman's recurrent adverse pregnancies and phenotypic abnormalities in her family members. The scoliosis identified in her younger brother has not been previously reported, thereby may enrich the clinical phenotype of this syndrome. For fetuses identified with a 22q11.2 microduplication, detailed fetal imaging is recommended, and genetic counseling should be provided to the couples.
Humans ; Female ; Pregnancy ; Prenatal Diagnosis/methods* ; Chromosome Duplication/genetics* ; Male ; Pedigree ; DiGeorge Syndrome/diagnosis* ; Adult ; Chromosomes, Human, Pair 22/genetics* ; Abnormalities, Multiple

Objective:This aims to investigate the diagnostic and evaluative value of MRI for lymphatic malformations in the head, neck, and facial regions of children. Methods:A retrospective analysis was conducted on the MRI imaging data of 31 cases of head, neck, and facial lymphatic malformations in children admitted to the Department of Otolaryngology, Head and Neck Surgery, Children's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, from January 2022 to January 2024. Results:The MRI images of this group of cases primarily displayed irregular morphology（80.6%, 25/31）, thin-walled cysts（80.6%, 25/31）, and compression of surrounding tissues. The boundaries were clear（100%, 31/31）, with characteristics of invasive and drill-like growth（93.5%）. The cyst walls or internal septa exhibited high signal intensity on T1WI, low signal intensity on T2WI, and mild to moderate enhancement（100%）. The contents of the cysts showed low signal intensity on T1WI, high signal intensity on T2WI, and no enhancement（35.5%, 11/31）. Mixed signals with varying degrees of enhancement were observed in 20 cases（64.5%）. There were 29 cases of multilocular cysts（93.5%, 29/31）, and 11 cases of fluid-fluid levels（35.5%）. The MRI diagnostic accuracy for this group of cases was 100%. Conclusion:Lymphatic Malformations of head, neck and facial region in children have very characteristic features on MRI, such as typical thin wall, clear boundaries, irregular shapes, invasive growth, no enhancement, multilocular cystic masses, fluid-fluid level, etc. Furthermore, it is more appropriate for children with lymphatic malformations owing to its non-radiation and non-invasive benefits. Diagnosing lymphatic malformations in the head, neck, and facial region in children should begin with this.
Humans ; Retrospective Studies ; Lymphatic Abnormalities/diagnostic imaging* ; Magnetic Resonance Imaging ; Neck/diagnostic imaging* ; Head/diagnostic imaging* ; Face/diagnostic imaging* ; Child ; Male ; Female ; Child, Preschool ; Adolescent ; Infant

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 assess the value of copy number variation sequencing (CNV-seq) for revealing the genetic etiology of fetuses with isolated ventricular septal defect (VSD). METHODS: From December 2017 to December 2020, 69 fetuses with isolated VSD were identified at the First Affiliated Hospital of Zhengzhou University. Meanwhile, 839 similar prenatal cases were selected from public databases including Wanfang data, Wanfang Medicine, and China National Knowledge Infrastructure (CNKI) by using keywords such as "Ventricular septal defect", "Copy number variation", and "Prenatal". A total of 908 fetuses with isolated VSD were analyzed. CNV-seq was carried out for 69 fetuses. RESULTS: Among the 908 fetuses, 33 (3.63%) were found to harbor pathogenic CNVs, which included 11 chromosomal aneuploidies (1.21%) and 22 pathogenic CNVs (2.42%). The pathogenic CNVs have involved 12 genetic syndromes, with those known to involve the heart development including 5 cases of 22q11.21 deletion syndrome, 2 cases of 4q terminal deletion syndrome, and 1 case of 9q subtelomere deletion syndrome. The outcome of pregnancies for 15 fetuses with pathogenic CNVs was known, of which 12 were terminated, and 3 had spontaneous closure of the ventricular septum after birth, but 1 of them had other abnormalities. CONCLUSION Fetuses with isolated VSD have a relatively high risk for chromosomal abnormalities, for which CNV-seq should be recommended.
Female ; Pregnancy ; Humans ; DNA Copy Number Variations ; Heart Septal Defects, Ventricular/genetics* ; 22q11 Deletion Syndrome ; Fetus

Humans ; DiGeorge Syndrome/diagnostic imaging* ; Tetralogy of Fallot/surgery* ; Ultrasonography

OBJECTIVE: To explore the cause for a twin pregnancy with false negative result for 22q11.2 deletion syndrome by expanded non-invasive prenatal testing (NIPT-plus). METHODS: A pregnant woman with twin pregnancy through in-vitro fertilization and negative result of NIPT-plus was selected as the study subject. Amniocentesis was conducted after ultrasonic finding of fetal abnormalities. In addition to conventional G-banded karyotyping, copy number variation sequencing (CNV-Seq) was used to detect chromosomal microdeletion and microduplication. Clinical data of the woman were analyzed to explore the reasons underlying the false negative result. RESULTS: NIPT-plus has yielded a negative result with 11.77 Mb unique reads and 3.05% fetal fraction. Both fetuses had a normal karyotype (46,XY and 46,XX). CNV-seq indicated that one of the fetuses was normal, whilst the other was diagnosed with a 2.58 Mb deletion in the 22q11.2 region. CONCLUSION The false negative result may be attributed to the combined influence of low fetal fraction, high BMI, twin pregnancy through IVF and a relatively small deletion fragment. Ultrasonography exam following a low-risk result of NIPT-plus should not be neglected.
Pregnancy ; Female ; Humans ; Prenatal Diagnosis ; Pregnancy, Twin/genetics* ; DiGeorge Syndrome/genetics* ; DNA Copy Number Variations ; Amniocentesis

Objective: To investigate the clinicopathological features, clinical manifestations and different diagnosis of patients with complicated lymphatic anomaly. Methods: The clinical and pathologic data of four patients with complicated lymphatic anomaly diagnosed and treated in Peking Union Medical College Hospital from January 2000 to December 2021 were collected and analyzed. Results: One Gorham-Stout disease case and three generalized lymphatic anomaly cases were included in this cohort. Patients' ages ranged from 7 to 32 years. There were three males and one female. The positions of biopsy included three bone biopsy and one bronchus biopsy. Microscopically, all cases showed diffuse enlarged lymphatic channels. At the same time, osteogenesis was obvious in Gorham-Stout disease case. Radiologically, cortical loss was seen in Gorham-Stout disease, and lytic bone confined to the medullary cavity presented in generalized lymphatic anomaly. The three generalized lymphatic anomaly cases also had coagulopathy, and two had effusion. Conclusions: The histologic feature of complicated lymphatic anomaly was diffuse lymphatic malformation, and the diagnosis depends on clinical and pathologic information. The treatment and prognosis of these diseases are different, and therefore it is necessary to understand their clinical and pathologic features and make the correct diagnosis.
Male ; Humans ; Female ; Child ; Adolescent ; Young Adult ; Adult ; Osteolysis, Essential/pathology* ; Lymphatic Abnormalities/surgery* ; Bone and Bones/pathology* ; Diagnosis, Differential ; Prognosis

CREB-Binding Protein/genetics* ; Humans ; Lymphangiectasis, Intestinal ; Rubinstein-Taybi Syndrome/genetics*

OBJECTIVE: To analyze the prenatal ultrasonic characteristics and genetic features of 14 fetuses with chromosome 22q11 microdeletion syndrome (22q11DS). METHODS: 4989 fetuses were analyzed by using single nucleotide polymorphism array (SNP array) in the Fujian Maternal and Child Health Hospital from November 2016 to November 2019. RESULTS: SNP array showed that 11 fetuses had classic 3 Mb microdeletion in 22q11 region, one fetus had 2.0 Mb microdeletion, and two fetuses had 1.0 Mb microdeletion. The 1.0 Mb microdeletion in 22q11 region contains SNAP29 and CRKL genes, which may increase the risk of congenital renal malformation and cardiovascular malformation. CONCLUSION Prenatal ultrasonic characteristics of fetuses with 22q11 microdeletion syndrome vary, and SNP array is a powerful tool to diagnose such diseases, which can provide accurate genetic diagnosis and enable prenatal diagnosis.
22q11 Deletion Syndrome/diagnostic imaging* ; Chromosome Deletion ; Chromosomes, Human, Pair 22/genetics* ; Female ; Fetus ; Genetic Testing ; Humans ; Pregnancy ; Prenatal Diagnosis ; Ultrasonics