Prenatal diagnosis of Kleefstra syndrome

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Christos G. Hatjis
Keyword(s):  
Prenatal Diagnosis ◽  
Amniotic Fluid ◽  
Microarray Analysis ◽  
Chromosomal Region ◽  
Loss Of Function ◽  
Fetal Ultrasound ◽  
Case Presentation ◽  
Place Of Delivery ◽  
Prenatal Diagnostic ◽  
Kleefstra Syndrome

AbstractObjectivesTo describe the prenatal diagnosis of Kleefstra syndrome (KS), a rare panethnic disorder characterized by mental and developmental delays, distinct facial features, congenital heart and urogenital defects, among others. KS is caused by haploinsusufficiency and loss of function of euchromatin histone methyltransferase 1 (EHMT1) due to deletions or mutations in the chromosomal region 9q34.3.Case presentationThe prenatal diagnosis of KS in this case report includes the description of subtle fetal phenotypic abnormalities detected by the fetal ultrasound examination as well as the results of the amniotic fluid microarray analysis that confirmed a fetal denovo deletion in the chromosomal region 9q34.3. These results confirmed the prenatal diagnosis of KS.ConclusionsThis case is noteworthy because of the late development of very subtle ultrasound abnormalities that triggered prenatal diagnostic studies in amniotic fluid cells, including SNP microarray analysis, that defined the diagnosis of KS. It allowed us to obtain the necessary antepartum consultations with neonatology, other pediatric subspecialties and arrange for the patient’s appropriate place of delivery to optimize the fetal and neonatal outcome.

Severe congenital non-syndromic ichthyosis: ultrasound diagnosis of a prenatal case

2019 ◽  
Vol 8 (2) ◽  
Author(s):  
Giulia Garofalo ◽  
Marie Cassart ◽  
Julie Désir ◽  
Dominique Thomas
Keyword(s):  
Prenatal Diagnosis ◽  
Family History ◽  
Genetic Diagnosis ◽  
Ultrasound Diagnosis ◽  
Second Trimester ◽  
Fetal Ultrasound ◽  
Case Presentation ◽  
Sonographic Diagnosis ◽  
Congenital Ichthyosis ◽  
Prenatal Genetic Diagnosis

Abstract Background Prenatal diagnosis of congenital ichthyosis is still a challenge and very few cases of sonographic diagnosis have been described in the literature. Diagnosis by fetal ultrasound is made from the late second trimester and prenatal genetic diagnosis can be possible only if a proband is known. Case presentation We report the case of a prenatal diagnosis of severe non-syndromic ichthyosis in a primigravida woman with no personal or family history for this pathology. Conclusion Our case outlines prenatal sonographic signs suggestive of ichthyosis orienting genetic diagnosis.

scholarly journals Prenatal diagnosis of megaduodenum using ultrasound: a case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kaihui Zeng ◽  
Dongmei Li ◽  
Yao Zhang ◽  
Chengcheng Cao ◽  
Ruobing Bai ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Case Report ◽  
Prenatal Diagnosis ◽  
Amniotic Fluid ◽  
Ultrasound Examination ◽  
Cystic Mass ◽  
Developmental Defect ◽  
Case Presentation ◽  
Amniotic Fluid Volume ◽  
Cystic Masses

Abstract Background Congenital megaduodenum is a rare disorder; however, its prenatal diagnosis has not been reported previously. We report the case of an abdominal cystic mass in a fetus that was later diagnosed as megaduodenum. Case presentation An abdominal cystic mass was found during ultrasonography of a fetus at 11 weeks of gestation. The mass progressively enlarged with gestation. The amniotic fluid volume decreased and then returned to normal. During the last prenatal ultrasound examination, the mass was observed communicating with the stomach; therefore, duodenal dilation was suspected. Finally, the patient was diagnosed with megaduodenum caused by a developmental defect in the nerve plexus. Conclusions Congenital megaduodenum is a differential diagnosis of massive fetal abdominal cystic masses. Ultrasound examinations of such masses communicating with the stomach may help determine the diagnosis.

scholarly journals Clinical Utility of the Prenatal BACs-on-Beads™ Assay in Invasive Prenatal Diagnosis

2022 ◽  
Vol 12 ◽  
Author(s):  
Yu Jiang ◽  
Lili Wu ◽  
Yunshen Ge ◽  
Jian Zhang ◽  
Yanru Huang ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Copy Number Variation ◽  
Copy Number ◽  
Clinical Utility ◽  
Clinical Pathways ◽  
Normal Karyotype ◽  
Fetal Ultrasound ◽  
Prenatal Diagnostic ◽  
Diagnostic Center ◽  
Number Variation

Background: The prenatal BACs-on-Beads™ (PNBoBs™) assay has been applied worldwide for prenatal diagnosis. However, there are neither guidelines nor consensus on choosing patients, sample types, or clinical pathways for using this technique. Moreover, different perspectives have emerged regarding its clinical value. This study aimed to evaluate its clinical utility in the context of clinical practice located in a prenatal diagnostic center in Xiamen, a city in southeast China.Methods: We tested 2,368 prenatal samples with multiple referral indications using both conventional karyotyping and PNBoBs™. Positive results from PNBoBs™ were verified using current gold-standard approaches.Results: The overall rates for the detection of pathogenic copy number variation (pCNV) by karyotyping and PNBoBs™ were 1.9% (46/2,368) and 2.0% (48/2,368), respectively. The overall detection rate of karyotyping combined with PNBoBs™ for pCNV was 2.3% (54/2,368). A total of 13 cases of copy number variation (CNV)with a normal karyotype were detected by PNBoBs™. Another case with a normal karyotype that was detected as a CNV of sex chromosomes by PNBoBs™ was validated to be maternal cell contamination by short tandem repeat analysis.Conclusion: Karyotyping combined with PNBoBs™ can improve both the yield and efficiency of prenatal diagnosis and is appropriate in the second trimester in all patients without fetal ultrasound anomalies who undergo invasive prenatal diagnosis.

scholarly journals Fetal chromosomal anomalies in southeast Serbia - single center cohort retrospective study

Genetika ◽  
2019 ◽  
Vol 51 (1) ◽  
pp. 157-166
Author(s):  
Radovan Milicevic ◽  
Ljiljana Brankovic ◽  
Desanka Radulovic ◽  
Dragana Jugovic ◽  
Hristina Stamenkovic ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Prenatal Diagnosis ◽  
Amniotic Fluid ◽  
Sex Chromosome ◽  
Chromosomal Anomalies ◽  
Amniotic Fluid Cell ◽  
Preventive Action ◽  
Isolated Cells ◽  
Prenatal Diagnostic ◽  
Numerical Aberrations

Congenital anomalies are the cause of prenatal death in 20-25% of the cases, while 3% of children are born with a malformation of varying size. Many of these anomalies can be detected before birth using different non-invasive and invasive prenatal diagnostic tests. This study was used to determine the distribution of genetic disorders in relation to the age of the mother, the frequency of aberrations and to study the effects and importance of prenatal diagnosis in South Serbia. Prenatal diagnostics was performed at the Pediatric Clinic within the Clinical Center of Nis. This retrospective study included a group of 8830 pregnant women, aged between 18 and 47 years during the period from 2004 to 2017. Amniocentesis was performed between the 16th and 18th week of pregnancy and involved the aspiration of 20 ml of amniotic fluid. Isolated cells were cultured in a medium that stimulates cell growth for 10 days. After cytogenetic processing, the obtained karyotype was analyzed using G-banding techniques. In 8830 samples of amniotic fluid cell cultures, 198 karyotypes with chromosomal aberrations were found - 179 with numerical aberrations and 19 with structural aberrations such as translocations, inversions and deletions. There were 85 karyotypes with autosomal numerical aberrations and 32 karyotypes with sex chromosome numerical aberrations. The most frequent one was trisomy 21 (106 cases). The highest number of autosomal numerical aberrations, 84%, was found in pregnancies where maternal age was above 30 years. Preventive action, advice, education and availability of prenatal diagnosis can lead to a significant reduction in the number of children born with various malformations.

scholarly journals Value of Amniotic Fluid Homocysteine Assay in Prenatal Diagnosis of Combined Methylmalonic Acidemia and Homocystinuria, Cobalamin C Type

2020 ◽  
Author(s):  
Ting Chen ◽  
Lili Liang ◽  
Huiwen Zhang ◽  
Jun Ye ◽  
Wenjuan Qiu ◽  
...  
Keyword(s):  
At Risk ◽  
Prenatal Diagnosis ◽  
Amniotic Fluid ◽  
Metabolite Profile ◽  
Methylmalonic Acidemia ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Prenatal Diagnostic ◽  
Cobalamin Metabolism ◽  
Fluid Levels

Abstract Background: Combined methylmalonic acidemia and homocystinuria, cobalamin C type (cblC defect) is the most common inborn error of cobalamin metabolism. Even with rapid diagnosis and treatment, the long-term outcome remains poor. A reliable method for the prenatal diagnosis of cblC defect is needed for parental decisions regarding continuation of pregnancies of cblC defect fetuses.Results: The between-day and within-day imprecision of Hcy assay were 1.60%∼5.87% and 1.11%∼4.31%, respectively. For the 248 at-risk fetuses, there were 63 affected fetuses with cblC defect and 185 unaffected fetuses. The levels of Hcy in 63 affected fetuses were significantly higher than those in 185 unaffected fetuses, without overlap between the affected and unaffected groups. Sixteen fetuses displayed inconclusive genetic results of MMACHC variants, in which seven fetuses were determined to be affected with elevated amniotic fluid levels of Hcy, C3, C3/C2 and MMA. The remaining nine fetuses were considered unaffected based on a normal amniotic fluid metabolite profile. The diagnostic sensitivities of Hcy and other characteristic metabolites including propionylcarnitine (C3), ratio of C3 to acetylcarnitine (C2; C3/C2), methylmalonic acid (MMA), and methylcitrate acid (MCA) in amniotic fluid were 100%, 87.50%, 100%, 85.71%, and 28.57%, respectively. The respective specificities were 92.05%, 100%, 100%, 97.73%, and 99.43%. Conclusions: Hcy appears to be another sensitive characteristic metabolite biomarker for the prenatal diagnosis of cblC defect. The combination of Hcy assay with acylcarnitine and organic acid analysis is a fast, sensitive, and reliable prenatal diagnostic biochemical approach. This approach could overcome the challenge of the lack of genetic analysis for families with at-risk cblC defect fetuses.

scholarly journals Value of amniotic fluid homocysteine assay in prenatal diagnosis of combined methylmalonic acidemia and homocystinuria, cobalamin C type

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Ting Chen ◽  
Lili Liang ◽  
Huiwen Zhang ◽  
Jun Ye ◽  
Wenjuan Qiu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
At Risk ◽  
Prenatal Diagnosis ◽  
Genetic Analysis ◽  
Amniotic Fluid ◽  
Organic Acid ◽  
Methylmalonic Acidemia ◽  
Predictive Values ◽  
Organic Acid Analysis ◽  
Prenatal Diagnostic

Abstract Background Combined methylmalonic acidemia and homocystinuria, cobalamin C type (cblC defect) is the most common inborn error of cobalamin metabolism, and different approaches have been applied to its prenatal diagnosis. To evaluate the reliability of biochemical method for the prenatal diagnosis of cblC defect, we conducted a retrospective study of our 10-year experience at a single center. Methods 248 pregnancies whose probands were diagnosed as cblC defect were referred to our center for prenatal diagnosis from January 2010 to December 2019. Prenatal data of Hcy levels determined by enzymatic cycling assay, acylcarnitine analysis using liquid chromatography tandem mass spectrometry, organic acid analysis using gas chromatography mass spectrometry, and genetic analysis by direct sequencing of 248 at-risk fetuses were retrospectively reviewed. Results For 2.0 and 16.0 μmol/L levels of Hcy AF samples, the relative errors were − 2.5% and 2.8%, respectively. The respective measurement uncertainties were 13.07% and 14.20%. For the 248 at-risk fetuses, 63 fetuses were affected and 185 fetuses were unaffected. Hcy level of 13.20 (6.62–43.30) μmol/L in 63 affected fetuses was significantly higher than that in 185 unaffected fetuses of 2.70 (0.00–5.80) μmol/L, and there was no overlap between the affected and unaffected groups. The diagnostic sensitivity and specificity of Hcy were 100% and 92.05%, respectively. The positive and negative predictive values of the combination of Hcy, propionylcarnitine (C3), ratio of C3 to acetylcarnitine (C2; C3/C2), methylmalonic acid (MMA), and methylcitric acid (MCA) were both 100%. Sixteen fetuses displayed inconclusive genetic results of MMACHC variants, in which seven fetuses were determined to be affected with elevated levels of Hcy, C3, C3/C2 and MMA, and their levels were 18.50 (6.70–43.30) μmol/L, 8.53(5.02–11.91) μmol/L, 0.77 (0.52–0.97), 8.96 (6.55–40.32) mmol/mol Cr, respectively. The remaining nine fetuses were considered unaffected based on a normal amniotic fluid metabolite profile. Conclusions Hcy appears to be another characteristic biomarker for the prenatal diagnosis of cblC defect. The combination of Hcy assay with acylcarnitine and organic acid analysis is a fast, sensitive, and reliable prenatal diagnostic biochemical approach. This approach could overcome the challenge of the lack of genetic analysis for families with at-risk cblC defect fetuses.

scholarly journals The Metabolic Bone Disease X-linked Hypophosphatemia: Case Presentation, Pathophysiology and Pharmacology

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 563
Author(s):  
Jon Vincze ◽  
Brian W. Skinner ◽  
Katherine A. Tucker ◽  
Kory A. Conaway ◽  
Jonathan W. Lowery ◽  
...  
Keyword(s):  
Vitamin D ◽  
Biological Effects ◽  
Fibroblast Growth Factor 23 ◽  
Elevated Serum ◽  
Fractional Excretion ◽  
The United States ◽  
Vitamin D Supplementation ◽  
Loss Of Function ◽  
Case Presentation ◽  
Serum Inorganic Phosphate

The authors present a stereotypical case presentation of X-linked hypophosphatemia (XLH) and provide a review of the pathophysiology and related pharmacology of this condition, primarily focusing on the FDA-approved medication burosumab. XLH is a renal phosphate wasting disorder caused by loss of function mutations in the PHEX gene (phosphate-regulating gene with homologies to endopeptidases on the X chromosome). Typical biochemical findings include elevated serum levels of bioactive/intact fibroblast growth factor 23 (FGF23) which lead to (i) low serum phosphate levels, (ii) increased fractional excretion of phosphate, and (iii) inappropriately low or normal 1,25-dihydroxyvitamin D (1,25-vitD). XLH is the most common form of heritable rickets and short stature in patients with XLH is due to chronic hypophosphatemia. Additionally, patients with XLH experience joint pain and osteoarthritis from skeletal deformities, fractures, enthesopathy, spinal stenosis, and hearing loss. Historically, treatment for XLH was limited to oral phosphate supplementation, active vitamin D supplementation, and surgical intervention for cases of severe bowed legs. In 2018, the United States Food and Drug Administration (FDA) approved burosumab for the treatment of XLH and this medication has demonstrated substantial benefit compared with conventional therapy. Burosumab binds circulating intact FGF23 and blocks its biological effects in target tissues, resulting in increased serum inorganic phosphate (Pi) concentrations and increased conversion of inactive vitamin D to active 1,25-vitD.

scholarly journals A Broader Perspective on the Prenatal Diagnosis of Cornelia de Lange Syndrome: Review of the Literature and Case Presentation

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 142
Author(s):  
Anca Maria Panaitescu ◽  
Simona Duta ◽  
Nicolae Gica ◽  
Radu Botezatu ◽  
Florina Nedelea ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Cornelia De Lange Syndrome ◽  
Facial Features ◽  
Genetic Condition ◽  
Case Presentation ◽  
Pathogenic Variants ◽  
Limb Reduction ◽  
Ultrasound Findings ◽  
Prenatal Management ◽  
Cornelia De Lange

Cornelia de Lange syndrome (CDLS) is caused by pathogenic variants in genes which are structural or regulatory components of the cohesin complex. The classical Cornelia de Lange (CDLS) phenotype is characterized by distinctive facial features, growth retardation, upper limb reduction defects, hirsutism, and developmental delay. Non-classical phenotypes make this condition heterogeneous. Although CDLS is a heterogeneous clinical and genetic condition, clear diagnostic criteria have been described by specialist consensus. Many of these criteria refer to features that can be seen on prenatal ultrasound. The aim of this paper is twofold: to present the ultrasound findings in fetuses affected by CDLS syndrome; to discuss the recent advances and the limitations in the ultrasound and genetic prenatal diagnosis of CDLS. Our review aims to offer, apart from the data needed to understand the genetics and the prenatal presentation of the disease, a joint perspective of the two specialists involved in the prenatal management of this pathology: the fetal medicine specialist and the geneticist. To better illustrate the data presented, we also include a representative clinical case.

scholarly journals Spondylocarpotarsal synostosis syndrome due to a novel loss of function FLNB variant: a case report

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Samina Yasin ◽  
Outi Makitie ◽  
Sadaf Naz
Keyword(s):  
Short Stature ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Loss Of Function ◽  
Case Presentation ◽  
Pathogenic Variants ◽  
Skeletal Malformations ◽  
Tarsal Bones ◽  
The Family ◽  
Heterozygous Carriers

Abstract Background Loss of function or gain of function variants of Filamin B (FLNB) cause recessive or dominant skeletal disorders respectively. Spondylocarpotarsal synostosis syndrome (SCT) is a rare autosomal recessive disorder characterized by short stature, fused vertebrae and fusion of carpal and tarsal bones. We present a novel FLNB homozygous pathogenic variant and present a carrier of the variant with short height. Case presentation We describe a family with five patients affected with skeletal malformations, short stature and vertebral deformities. Exome sequencing revealed a novel homozygous frameshift variant c.2911dupG p.(Ala971GlyfsTer122) in FLNB, segregating with the phenotype in the family. The variant was absent in public databases and 100 ethnically matched control chromosomes. One of the heterozygous carriers of the variant had short stature. Conclusion Our report expands the genetic spectrum of FLNB pathogenic variants. It also indicates a need to assess the heights of other carriers of FLNB recessive variants to explore a possible role in idiopathic short stature.

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