Rachel A Veazey, Allan J Fisher, Asha N Talati, Emily Hardisty, Kelly L Gilmore, Neeta L Vora
{"title":"Novel Missense Variant in the SMARCD1 Gene as the Cause of Coffin-Siris Syndrome 11 in a Fetus With Ambiguous Genitalia and Multiple Dysmorphic Features.","authors":"Rachel A Veazey, Allan J Fisher, Asha N Talati, Emily Hardisty, Kelly L Gilmore, Neeta L Vora","doi":"10.1002/pd.6683","DOIUrl":"10.1002/pd.6683","url":null,"abstract":"","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emma Van den Eede, Simen Vergote, Lennart Van der Veeken, Francesca Russo, Johannes Van der Merwe, Sofia Mastrodima-Polychroniou, Luc De Catte, Jan Deprest
Objective: The severity of spina bifida aperta can be assessed prenatally by ultrasound. Morphological findings assist parents in choosing between management options. We aimed to document those management choices since the introduction of fetal surgery, and compare initial ultrasound findings prior to referral to findings in a fetal surgery center.
Method: Single center cohort study of 245 consecutive fetuses with a second-trimester diagnosis of SBA. Data included nature of referral (for assessment or for surgery), condition-specific findings on ultrasound, and further management. We compared the reported findings on the initial ultrasound to ours for the presence of hindbrain herniation, lesion level, ventricular width, kyphosis, leg movement, and club feet.
Results: Seventy-two percent (n = 177) of fetuses met the eligibility criteria for surgery; in 60% (n = 106) parents opted for fetal surgery. Of 136 patients specifically referred for surgery, 27 were ineligible (20%). Of the others, 93 proceeded with surgery. In up to 28% (n = 30) of surgery referrals, eligibility criteria such as lesion level (n = 30, 28%) or leg movement (72%, n = 78) as severity indicators were not reported.
Conclusion: Fetal surgery uptake was high in patients referred for surgery. Second assessment in a fetal surgery center often reveals additional relevant information.
{"title":"Parental Management Choices and Discordant Ultrasound Findings in Referrals for Fetal Spina Bifida.","authors":"Emma Van den Eede, Simen Vergote, Lennart Van der Veeken, Francesca Russo, Johannes Van der Merwe, Sofia Mastrodima-Polychroniou, Luc De Catte, Jan Deprest","doi":"10.1002/pd.6677","DOIUrl":"https://doi.org/10.1002/pd.6677","url":null,"abstract":"<p><strong>Objective: </strong>The severity of spina bifida aperta can be assessed prenatally by ultrasound. Morphological findings assist parents in choosing between management options. We aimed to document those management choices since the introduction of fetal surgery, and compare initial ultrasound findings prior to referral to findings in a fetal surgery center.</p><p><strong>Method: </strong>Single center cohort study of 245 consecutive fetuses with a second-trimester diagnosis of SBA. Data included nature of referral (for assessment or for surgery), condition-specific findings on ultrasound, and further management. We compared the reported findings on the initial ultrasound to ours for the presence of hindbrain herniation, lesion level, ventricular width, kyphosis, leg movement, and club feet.</p><p><strong>Results: </strong>Seventy-two percent (n = 177) of fetuses met the eligibility criteria for surgery; in 60% (n = 106) parents opted for fetal surgery. Of 136 patients specifically referred for surgery, 27 were ineligible (20%). Of the others, 93 proceeded with surgery. In up to 28% (n = 30) of surgery referrals, eligibility criteria such as lesion level (n = 30, 28%) or leg movement (72%, n = 78) as severity indicators were not reported.</p><p><strong>Conclusion: </strong>Fetal surgery uptake was high in patients referred for surgery. Second assessment in a fetal surgery center often reveals additional relevant information.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jean-Marie Jouannic, Eléonore Blondiaux, Timothée de Saint-Denis, Pauline Lallemant, Catherine Garel
{"title":"Response to: Prenatal Diagnosis and Postnatal Outcome of Closed Spinal Dysraphism, by Bedei et al.","authors":"Jean-Marie Jouannic, Eléonore Blondiaux, Timothée de Saint-Denis, Pauline Lallemant, Catherine Garel","doi":"10.1002/pd.6685","DOIUrl":"https://doi.org/10.1002/pd.6685","url":null,"abstract":"","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yoann Athiel, Jean-Marie Jouannic, Matthieu Lépine, Corentin Maillet, Timothée de Saint Denis, Jérôme Larghero, Lucie Guilbaud
Myelomeningocele is a birth defect whose clinical manifestations are due both to incomplete neural tube closure and the progressive destruction of exposed neuroepithelium during pregnancy. Two hypotheses have been formulated to explain the spinal cord damage in utero: mechanical trauma and chemical factors. The objective of this review was to summarize the current insights about the potential role of amniotic fluid in spinal cord damage in myelomeningocele. Numerous histological and clinical data on animals and humans strongly suggest a progressive degeneration of neural tissue including loss of neural cells, astrogliosis, inflammation, and loss of normal architecture. However, few data have been published about the direct toxicity of amniotic fluid in this neural degeneration, including the potentially toxic effect of meconium. Finally, the chemical and cellular modifications of amniotic fluid composition in myelomeningocele could reflect both the process (toxic effect of meconium) and the consequences of neuroepithelium destruction (release of neural cells). Fetal surgery not only stops the leakage of the cerebrospinal fluid but also reduces the toxic effect of amniotic fluid by restoring the intrauterine environment. Identification of amniotic fluid neurotoxic factors could lead to the development of therapeutic agents designed to protect spinal tissue and improve fetal myelomeningocele outcomes.
{"title":"Role of Amniotic Fluid Toxicity in the Pathophysiology of Myelomeningocele: A Narrative Literature Review.","authors":"Yoann Athiel, Jean-Marie Jouannic, Matthieu Lépine, Corentin Maillet, Timothée de Saint Denis, Jérôme Larghero, Lucie Guilbaud","doi":"10.1002/pd.6681","DOIUrl":"https://doi.org/10.1002/pd.6681","url":null,"abstract":"<p><p>Myelomeningocele is a birth defect whose clinical manifestations are due both to incomplete neural tube closure and the progressive destruction of exposed neuroepithelium during pregnancy. Two hypotheses have been formulated to explain the spinal cord damage in utero: mechanical trauma and chemical factors. The objective of this review was to summarize the current insights about the potential role of amniotic fluid in spinal cord damage in myelomeningocele. Numerous histological and clinical data on animals and humans strongly suggest a progressive degeneration of neural tissue including loss of neural cells, astrogliosis, inflammation, and loss of normal architecture. However, few data have been published about the direct toxicity of amniotic fluid in this neural degeneration, including the potentially toxic effect of meconium. Finally, the chemical and cellular modifications of amniotic fluid composition in myelomeningocele could reflect both the process (toxic effect of meconium) and the consequences of neuroepithelium destruction (release of neural cells). Fetal surgery not only stops the leakage of the cerebrospinal fluid but also reduces the toxic effect of amniotic fluid by restoring the intrauterine environment. Identification of amniotic fluid neurotoxic factors could lead to the development of therapeutic agents designed to protect spinal tissue and improve fetal myelomeningocele outcomes.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hadas Miremberg, Roee Birnbaum, Dorin Trigubov, Adi Botvinik, Yuval Yaron, Adi Mory, Gustavo Malinger, Karina Krajden Haratz
Following termination of pregnancy due to multiple brain malformations, a non-consanguineous couple of Jewish descent sought genetic counseling. Brain malformations identified on neurosonogram included corpus callosum dysgenesis, abnormal brain stem morphology, abnormal cortical sulcation and hypertelorism. Trio exome sequencing revealed a heterozygous de novo likely pathogenic variant in KIDINS220 gene. Heterozygous variants in KIDINS220 have been linked to spastic paraplegia, intellectual disability, nystagmus, and obesity syndrome (SINO). Reports on prenatal findings are limited and primarily consist of cases of ventriculomegaly. We describe a more severe clinical presentation in a case with a heterozygous variant.
{"title":"Prenatal Diagnosis of a KIDINS220 De Novo Heterozygous Variant in a Fetus With a Complex CNS Anomaly.","authors":"Hadas Miremberg, Roee Birnbaum, Dorin Trigubov, Adi Botvinik, Yuval Yaron, Adi Mory, Gustavo Malinger, Karina Krajden Haratz","doi":"10.1002/pd.6682","DOIUrl":"https://doi.org/10.1002/pd.6682","url":null,"abstract":"<p><p>Following termination of pregnancy due to multiple brain malformations, a non-consanguineous couple of Jewish descent sought genetic counseling. Brain malformations identified on neurosonogram included corpus callosum dysgenesis, abnormal brain stem morphology, abnormal cortical sulcation and hypertelorism. Trio exome sequencing revealed a heterozygous de novo likely pathogenic variant in KIDINS220 gene. Heterozygous variants in KIDINS220 have been linked to spastic paraplegia, intellectual disability, nystagmus, and obesity syndrome (SINO). Reports on prenatal findings are limited and primarily consist of cases of ventriculomegaly. We describe a more severe clinical presentation in a case with a heterozygous variant.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sarah van den Wildenberg, Ingrid M van Beynum, Malou E C Havermans, Eric Boersma, Greggory R DeVore, John M Simpson, Eric A P Steegers, Attie T J I Go, Jérôme M J Cornette
Fetal two-dimensional speckle tracking echocardiography (2D-STE) is a novel technique that provides information on fetal heart function by measuring global longitudinal strain (GLS) and global longitudinal strain rate (GLSR). These features assess the longitudinal deformity of the fetal cardiac wall. 2D-STE is shown to be of prognostic value in children and adults with congenital heart disease (CHD). Therefore, its importance in fetal life should also be considered. This systematic review and meta-analysis provides an overview of the literature on 2D-STE (GLS/GLSR) in fetuses with CHD, focusing on the left and right ventricles (LV/RV). Findings indicated that LV-GLS was significantly lower in fetuses with coarctation of the aorta (CoA) and Tetralogy of Fallot (ToF) compared to controls. Conversely, fetuses with a single left ventricle exhibited higher LV-GLS. RV-GLS was significantly lower in fetuses with hypoplastic left heart syndrome (HLHS) and ToF compared to controls. LV-GLSR was significantly lower in fetuses with CoA. Overall, considerable heterogeneity was observed, possibly due to differences in study design. More prospective longitudinal studies on 2D-STE in fetuses with CHD, considering heterogeneity parameters, could offer better insights into this promising technique.
{"title":"Fetal Speckle Tracking Echocardiography Measured Global Longitudinal Strain and Strain Rate in Congenital Heart Disease: A Systematic Review and Meta-Analysis.","authors":"Sarah van den Wildenberg, Ingrid M van Beynum, Malou E C Havermans, Eric Boersma, Greggory R DeVore, John M Simpson, Eric A P Steegers, Attie T J I Go, Jérôme M J Cornette","doi":"10.1002/pd.6672","DOIUrl":"https://doi.org/10.1002/pd.6672","url":null,"abstract":"<p><p>Fetal two-dimensional speckle tracking echocardiography (2D-STE) is a novel technique that provides information on fetal heart function by measuring global longitudinal strain (GLS) and global longitudinal strain rate (GLSR). These features assess the longitudinal deformity of the fetal cardiac wall. 2D-STE is shown to be of prognostic value in children and adults with congenital heart disease (CHD). Therefore, its importance in fetal life should also be considered. This systematic review and meta-analysis provides an overview of the literature on 2D-STE (GLS/GLSR) in fetuses with CHD, focusing on the left and right ventricles (LV/RV). Findings indicated that LV-GLS was significantly lower in fetuses with coarctation of the aorta (CoA) and Tetralogy of Fallot (ToF) compared to controls. Conversely, fetuses with a single left ventricle exhibited higher LV-GLS. RV-GLS was significantly lower in fetuses with hypoplastic left heart syndrome (HLHS) and ToF compared to controls. LV-GLSR was significantly lower in fetuses with CoA. Overall, considerable heterogeneity was observed, possibly due to differences in study design. More prospective longitudinal studies on 2D-STE in fetuses with CHD, considering heterogeneity parameters, could offer better insights into this promising technique.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375835","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yarin Mash, Ron Bardin, Yinon Gilboa, Yosi Geron, Asaf Romano, Eran Hadar, Dana Brabbing Goldstein, Bella Davidov, Ohad Houri
Objective: To investigate the association of agenesis of the ductus venosus (ADV) with genetic abnormalities using genetic studies-Chromosomal Microarray Analysis (CMA) and Exome Sequencing (ES).
Design: Retrospective study of all fetuses diagnosed with ADV between January 2013 and December 2022 in a tertiary center.
Results: ADV was diagnosed in 33 fetuses. The diagnosis was made at a mean gestational age of 21.2 ± 8.4 weeks. Conventional karyotype was applied in a single fetus (3.0%), CMA was applied in 21 fetuses (66.7%), and five fetuses (22.8%) were additionally tested with ES. ADV was isolated in eight fetuses (24%), whereas in 25 (76%) it was associated with abnormal ultrasound findings, including increased nuchal translucency (NT), intrauterine growth restriction (IUGR) and variable structural malformations, mostly cardiac (42%) followed by central nervous system (CNS) and skeletal malformations (24%). Genetic abnormalities were found in six fetuses out of 22 investigated (27%), of which 3 were detected by ES, 3 by CMA and 1 by conventional karyotype. A higher incidence of genetic aberrations was evident among ADVs associated with abnormal ultrasound findings. Genetic abnormalities were indicative of Prader Willi/Angelman syndrome, Noonan syndrome, CASK related disorder, 16q24.3 microdeletion syndrome and Trisomy 21.
Conclusion: ADV associated with abnormal ultrasound findings is commonly correlated with genetic abnormalities and consequently unfavorable pregnancy outcomes. Our study emphasizes the value of genetic studies chiefly among cases associated with abnormal ultrasound findings, enabling early diagnosis of fetal pathologies associated with ADV, and providing better parental counseling.
{"title":"Agenesis of the Ductus Venosus and Its Association With Genetic Abnormalities.","authors":"Yarin Mash, Ron Bardin, Yinon Gilboa, Yosi Geron, Asaf Romano, Eran Hadar, Dana Brabbing Goldstein, Bella Davidov, Ohad Houri","doi":"10.1002/pd.6678","DOIUrl":"https://doi.org/10.1002/pd.6678","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the association of agenesis of the ductus venosus (ADV) with genetic abnormalities using genetic studies-Chromosomal Microarray Analysis (CMA) and Exome Sequencing (ES).</p><p><strong>Design: </strong>Retrospective study of all fetuses diagnosed with ADV between January 2013 and December 2022 in a tertiary center.</p><p><strong>Results: </strong>ADV was diagnosed in 33 fetuses. The diagnosis was made at a mean gestational age of 21.2 ± 8.4 weeks. Conventional karyotype was applied in a single fetus (3.0%), CMA was applied in 21 fetuses (66.7%), and five fetuses (22.8%) were additionally tested with ES. ADV was isolated in eight fetuses (24%), whereas in 25 (76%) it was associated with abnormal ultrasound findings, including increased nuchal translucency (NT), intrauterine growth restriction (IUGR) and variable structural malformations, mostly cardiac (42%) followed by central nervous system (CNS) and skeletal malformations (24%). Genetic abnormalities were found in six fetuses out of 22 investigated (27%), of which 3 were detected by ES, 3 by CMA and 1 by conventional karyotype. A higher incidence of genetic aberrations was evident among ADVs associated with abnormal ultrasound findings. Genetic abnormalities were indicative of Prader Willi/Angelman syndrome, Noonan syndrome, CASK related disorder, 16q24.3 microdeletion syndrome and Trisomy 21.</p><p><strong>Conclusion: </strong>ADV associated with abnormal ultrasound findings is commonly correlated with genetic abnormalities and consequently unfavorable pregnancy outcomes. Our study emphasizes the value of genetic studies chiefly among cases associated with abnormal ultrasound findings, enabling early diagnosis of fetal pathologies associated with ADV, and providing better parental counseling.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Keying Li, Huilin Wang, Matthew Hoi Kin Chau, Zirui Dong, Ye Cao, Yu Zheng, Tak Yeung Leung, Kwong Wai Choy, Yuanfang Zhu
Objectives: To investigate the diagnostic utility of copy-number variant (CNV) detection by chromosomal microarray analysis (CMA) and genotype-phenotype associations in prenatal congenital anomalies of the kidney and urinary tract (CAKUT).
Methods: This is a retrospective multi-center study of CNV analysis in 457 fetuses with ultrasound-detected CAKUT and normal karyotypes. Cohorts from published studies were included for further pooled analyses (N = 2746). A literature review of single-nucleotide variant (SNV) and small insertions and deletions (Indel) analysis by whole-exome sequencing was performed to investigate monogenic causes.
Results: In our multi-center cohort, 5.3% (24/457) of fetuses had pathogenic CNVs (pCNV); 3.9% (14/359) and 10.2% (10/98) in isolated and non-isolated CAKUT, respectively. Fetuses with isolated hyperechogenic kidneys (HEK) had the highest incidence of having pCNVs. In the literature review, 6.6% (180/2746) of fetuses carried pCNVs; 6.1% and 7.5% in isolated and non-isolated CAKUT, respectively. SNV/Indel analysis provided at least 16.5% (63/381) additional diagnostic yield beyond CNV analysis; 12.8% and 23.8% in isolated and non-isolated CAKUT, respectively.
Conclusion: pCNVs comprise a significant proportion of genetic diagnostic findings in prenatal CAKUT, most commonly detected in fetuses with isolated HEK, MCDK, renal agenesis, and non-isolated CAKUT. Monogenic causes should be considered when karyotyping and CMA are nondiagnostic.
{"title":"Contribution of Genomic Imbalance in Prenatal Congenital Anomalies of the Kidney and Urinary Tract: A Multi-Center Cohort Study.","authors":"Keying Li, Huilin Wang, Matthew Hoi Kin Chau, Zirui Dong, Ye Cao, Yu Zheng, Tak Yeung Leung, Kwong Wai Choy, Yuanfang Zhu","doi":"10.1002/pd.6674","DOIUrl":"https://doi.org/10.1002/pd.6674","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the diagnostic utility of copy-number variant (CNV) detection by chromosomal microarray analysis (CMA) and genotype-phenotype associations in prenatal congenital anomalies of the kidney and urinary tract (CAKUT).</p><p><strong>Methods: </strong>This is a retrospective multi-center study of CNV analysis in 457 fetuses with ultrasound-detected CAKUT and normal karyotypes. Cohorts from published studies were included for further pooled analyses (N = 2746). A literature review of single-nucleotide variant (SNV) and small insertions and deletions (Indel) analysis by whole-exome sequencing was performed to investigate monogenic causes.</p><p><strong>Results: </strong>In our multi-center cohort, 5.3% (24/457) of fetuses had pathogenic CNVs (pCNV); 3.9% (14/359) and 10.2% (10/98) in isolated and non-isolated CAKUT, respectively. Fetuses with isolated hyperechogenic kidneys (HEK) had the highest incidence of having pCNVs. In the literature review, 6.6% (180/2746) of fetuses carried pCNVs; 6.1% and 7.5% in isolated and non-isolated CAKUT, respectively. SNV/Indel analysis provided at least 16.5% (63/381) additional diagnostic yield beyond CNV analysis; 12.8% and 23.8% in isolated and non-isolated CAKUT, respectively.</p><p><strong>Conclusion: </strong>pCNVs comprise a significant proportion of genetic diagnostic findings in prenatal CAKUT, most commonly detected in fetuses with isolated HEK, MCDK, renal agenesis, and non-isolated CAKUT. Monogenic causes should be considered when karyotyping and CMA are nondiagnostic.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01Epub Date: 2024-09-03DOI: 10.1002/pd.6637
Stephanie M Rice, Dante F Varotsis, Sascha Wodoslawsky, Elizabeth Critchlow, Ruby Liu, Rodney A McLaren, Mona M Makhamreh, Brandy Firman, Seth I Berger, Huda B Al-Kouatly
Alkuraya-Kučinskas syndrome (AKS) is an autosomal recessive multisystem disorder resulting from mutations in the BLTP1 gene, formerly known as KIAA1109. Primary manifestations include brain malformations, arthrogryposis, and clubfeet. Cardiac, renal, and ophthalmologic abnormalities may also be observed, while nonimmune hydrops is rare. We present a case of two novel BLTP1 canonical splice-site variants in a fetus with multiple congenital anomalies, including hydrops, a kinked brainstem, and joint contractures. A systematic literature review was conducted to describe the prenatal phenotype of AKS, which was inspired by our case. Our systematic literature review of the prenatal phenotype in 19 cases, including our additional case, demonstrated joint contractures in 90% (18/20), ventriculomegaly in 60% (12/20), brainstem dysgenesis in 50% (10/20), cerebellar hypoplasia in 50% (10/20), parenchymal thinning with lissencephalic aspect in 60% (12/20), and facial dysmorphism in 70% (14/20) of reported AKS cases. In addition to our case, hydrops was reported in two other families. AKS should be considered in fetal presentations with characteristic features, especially brainstem kinking and joint contractures. Exome sequencing, including coverage of canonical intronic splice-site variants, can clarify the diagnosis. TRIAL REGISTRATION: ClinicalTrials.gov registration: NCT03911531.
阿尔库拉亚-库钦斯卡斯综合征(AKS)是一种常染色体隐性遗传的多系统疾病,由 BLTP1 基因(原名 KIAA1109)突变引起。主要表现包括脑畸形、关节发育不良和足外翻。也可能出现心脏、肾脏和眼科异常,而非免疫性水肿则很少见。我们报告了一例有两个新型 BLTP1 同源剪接位点变异的胎儿,该胎儿有多种先天性畸形,包括水肿、脑干扭转和关节挛缩。受我们的病例启发,我们对 AKS 的产前表型进行了系统的文献综述。我们对 19 个病例(包括我们的病例)的产前表型进行了系统性文献回顾,结果显示,在已报道的 AKS 病例中,90%(18/20)的病例存在关节挛缩,60%(12/20)的病例存在脑室肥大,50%(10/20)的病例存在脑干发育不良,50%(10/20)的病例存在小脑发育不全,60%(12/20)的病例存在脑实质变薄,70%(14/20)的病例存在面部畸形。除我们的病例外,另有两个家族报告了水肿。如果胎儿出现特征性表现,尤其是脑干扭转和关节挛缩,应考虑AKS。外显子组测序(包括典型的内含子剪接位点变异)可明确诊断。试验注册:ClinicalTrials.gov 注册:NCT03911531。
{"title":"Prenatal Phenotype of Alkuraya-Kučinskas Syndrome: A Novel Case and Systematic Literature Review.","authors":"Stephanie M Rice, Dante F Varotsis, Sascha Wodoslawsky, Elizabeth Critchlow, Ruby Liu, Rodney A McLaren, Mona M Makhamreh, Brandy Firman, Seth I Berger, Huda B Al-Kouatly","doi":"10.1002/pd.6637","DOIUrl":"10.1002/pd.6637","url":null,"abstract":"<p><p>Alkuraya-Kučinskas syndrome (AKS) is an autosomal recessive multisystem disorder resulting from mutations in the BLTP1 gene, formerly known as KIAA1109. Primary manifestations include brain malformations, arthrogryposis, and clubfeet. Cardiac, renal, and ophthalmologic abnormalities may also be observed, while nonimmune hydrops is rare. We present a case of two novel BLTP1 canonical splice-site variants in a fetus with multiple congenital anomalies, including hydrops, a kinked brainstem, and joint contractures. A systematic literature review was conducted to describe the prenatal phenotype of AKS, which was inspired by our case. Our systematic literature review of the prenatal phenotype in 19 cases, including our additional case, demonstrated joint contractures in 90% (18/20), ventriculomegaly in 60% (12/20), brainstem dysgenesis in 50% (10/20), cerebellar hypoplasia in 50% (10/20), parenchymal thinning with lissencephalic aspect in 60% (12/20), and facial dysmorphism in 70% (14/20) of reported AKS cases. In addition to our case, hydrops was reported in two other families. AKS should be considered in fetal presentations with characteristic features, especially brainstem kinking and joint contractures. Exome sequencing, including coverage of canonical intronic splice-site variants, can clarify the diagnosis. TRIAL REGISTRATION: ClinicalTrials.gov registration: NCT03911531.</p>","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Abstracts of the ISPD 28th International Conference on Prenatal Diagnosis and Therapy, 7-10 July 2024, Boston.","authors":"","doi":"10.1002/pd.6666","DOIUrl":"https://doi.org/10.1002/pd.6666","url":null,"abstract":"","PeriodicalId":20387,"journal":{"name":"Prenatal Diagnosis","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142472963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}