Biotinidase (BTD) deficiency is a rare autosomal recessive metabolic disorder caused by insufficient biotin metabolism, where it cannot recycle the vitamin biotin. When this deficiency is not treated with supplements, it can lead to severe neurological conditions. Approximately 1 in 60,000 newborns are affected by BTD deficiency. The BTD deficiency causes late-onset biotin-responsive multiple carboxylase deficiency, which leads to acidosis or lactic acidosis, hypoglycemia, and abnormal catabolism. BTD deficiency is of two types based on the amount of BTD Enzyme present in the serum. A wide range of pathogenic mutations in the BTD gene are reported worldwide. Mutations in the BTD gene lead to profound and partial BTD deficiency. Profound BTD deficiency results in a severe pathogenic condition. A high frequency of newborns are affected with the partial deficiency worldwide. They are mostly asymptomatic, but symptoms may appear during stressful conditions such as fasting or viral infections. Several pathogenic mutations are significantly associated with neurological, ophthalmological, and skin problems along with several other clinical features. This review discusses the BTD gene mutation in multiple populations detected with phenotypic features. The molecular-based biomarker screening is necessary for the disease during pregnancy, as it could be helpful for the early identification of BTD deficiency, providing a better treatment strategy. Moreover, implementing newborn screening for the BTD deficiency helps patients prevent several diseases.
{"title":"A Rare Biotinidase Deficiency in the Pediatrics Population: Genotype-Phenotype Analysis.","authors":"Balachander Kannan, Hepzibah Kirubamani Navamani, Vijayashree Priyadharsini Jayaseelan, Paramasivam Arumugam","doi":"10.1055/s-0042-1757887","DOIUrl":"10.1055/s-0042-1757887","url":null,"abstract":"<p><p>Biotinidase (BTD) deficiency is a rare autosomal recessive metabolic disorder caused by insufficient biotin metabolism, where it cannot recycle the vitamin biotin. When this deficiency is not treated with supplements, it can lead to severe neurological conditions. Approximately 1 in 60,000 newborns are affected by BTD deficiency. The BTD deficiency causes late-onset biotin-responsive multiple carboxylase deficiency, which leads to acidosis or lactic acidosis, hypoglycemia, and abnormal catabolism. BTD deficiency is of two types based on the amount of BTD Enzyme present in the serum. A wide range of pathogenic mutations in the <i>BTD</i> gene are reported worldwide. Mutations in the <i>BTD</i> gene lead to profound and partial BTD deficiency. Profound BTD deficiency results in a severe pathogenic condition. A high frequency of newborns are affected with the partial deficiency worldwide. They are mostly asymptomatic, but symptoms may appear during stressful conditions such as fasting or viral infections. Several pathogenic mutations are significantly associated with neurological, ophthalmological, and skin problems along with several other clinical features. This review discusses the <i>BTD</i> gene mutation in multiple populations detected with phenotypic features. The molecular-based biomarker screening is necessary for the disease during pregnancy, as it could be helpful for the early identification of BTD deficiency, providing a better treatment strategy. Moreover, implementing newborn screening for the BTD deficiency helps patients prevent several diseases.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"12 1","pages":"1-15"},"PeriodicalIF":0.4,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9848769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9132324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chromatinopathy is an emerging category of multiple malformation syndromes caused by disruption in global transcriptional regulation with imbalances in the chromatin states (i.e., open or closed chromatin). These syndromes are caused by pathogenic variants in genes coding for the writers, erasers, readers, and remodelers of the epigenetic machinery. Majority of these disorders (93%) show neurological dysfunction in the form of intellectual disability. Other overlapping features are growth abnormalities, limb deformities, and immune dysfunction. In this study, we describe a series of children with six common chromatinopathy syndromes with an aim to develop pattern recognition of this emerging category of multiple malformation syndromes.
{"title":"Pattern Recognition of Common Multiple Congenital Malformation Syndromes with Underlying Chromatinopathy.","authors":"Anupriya Kaur, Chakshu Chaudhry, Parminder Kaur, Roshan Daniel, Priyanka Srivastava","doi":"10.1055/s-0042-1748019","DOIUrl":"https://doi.org/10.1055/s-0042-1748019","url":null,"abstract":"<p><p>Chromatinopathy is an emerging category of multiple malformation syndromes caused by disruption in global transcriptional regulation with imbalances in the chromatin states (i.e., open or closed chromatin). These syndromes are caused by pathogenic variants in genes coding for the writers, erasers, readers, and remodelers of the epigenetic machinery. Majority of these disorders (93%) show neurological dysfunction in the form of intellectual disability. Other overlapping features are growth abnormalities, limb deformities, and immune dysfunction. In this study, we describe a series of children with six common chromatinopathy syndromes with an aim to develop pattern recognition of this emerging category of multiple malformation syndromes.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"13 1","pages":"6-14"},"PeriodicalIF":0.4,"publicationDate":"2022-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10984715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140857317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ceroid Lipofuscinosis in Children: Author's Reply.","authors":"Vykuntaraju K Gowda","doi":"10.1055/s-0042-1748157","DOIUrl":"https://doi.org/10.1055/s-0042-1748157","url":null,"abstract":"","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"11 2","pages":"172"},"PeriodicalIF":0.4,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9236753/pdf/10-1055-s-0042-1748157.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9395157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fibropolycystic diseases of the liver comprise a spectrum of disorders affecting bile ducts of various sizes and arise due to an underlying ductal plate malformation (DPM). We encountered a previously unreported variant of DPM, the hilar fibropolycystic disease which we diagnosed in the explant liver. A 2-year-old boy was referred for liver transplantation with a diagnosis of biliary atresia (BA) and failed Kasai portoenterostomy (KPE). He had cirrhosis with portal hypertension along with synthetic failure indicated by coagulopathy and hypoalbuminemia. The child underwent liver transplant successfully. The explant liver had fibropolycystic disease confined to the perihilar liver and hilum. No pathogenic mutation was detected by whole exome sequencing. Fibropolycystic liver disease may represent a peculiar anatomical variant, which can be diagnosed by careful pathological examination of the explant liver. The neonatal presentation of hilar fibropolycystic liver disease can be misdiagnosed as BA.
{"title":"Hilar Fibropolycystic Liver Disease of Unknown Etiology: A Revelation from the Explant Liver.","authors":"Jagadeesh Menon, Mukul Vij, Naresh Shanmugam, Abdul Hakeem, Mettu Srinivas Reddy, Ilankumaran Kaliamoorthy, Mohamed Rela","doi":"10.1055/s-0040-1716829","DOIUrl":"https://doi.org/10.1055/s-0040-1716829","url":null,"abstract":"<p><p>Fibropolycystic diseases of the liver comprise a spectrum of disorders affecting bile ducts of various sizes and arise due to an underlying ductal plate malformation (DPM). We encountered a previously unreported variant of DPM, the hilar fibropolycystic disease which we diagnosed in the explant liver. A 2-year-old boy was referred for liver transplantation with a diagnosis of biliary atresia (BA) and failed Kasai portoenterostomy (KPE). He had cirrhosis with portal hypertension along with synthetic failure indicated by coagulopathy and hypoalbuminemia. The child underwent liver transplant successfully. The explant liver had fibropolycystic disease confined to the perihilar liver and hilum. No pathogenic mutation was detected by whole exome sequencing. Fibropolycystic liver disease may represent a peculiar anatomical variant, which can be diagnosed by careful pathological examination of the explant liver. The neonatal presentation of hilar fibropolycystic liver disease can be misdiagnosed as BA.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"11 2","pages":"165-170"},"PeriodicalIF":0.4,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9236736/pdf/10-1055-s-0040-1716829.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10486030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Congenital nonsyndromic hearing loss (NSHL) has been considered as one of the most prevalent chronic disorder in children. It affects the physical and mental conditions of a large children population worldwide. Because of the genetic heterogeneity, the identification of target gene is very challenging. However, gap junction β-2 ( GJB2 ) is taken as the key gene for hearing loss, as its involvement has been reported frequently in NSHL cases. This study aimed to identify the association of GJB2 mutants in different Indian populations based on published studies in Indian population. This will provide clear genetic fundamental of NSHL in Indian biogeography, which would be helpful in the diagnosis process.
{"title":"Genetics Landscape of Nonsyndromic Hearing Loss in Indian Populations.","authors":"Manisha Ray, Saurav Sarkar, Mukund Namdev Sable","doi":"10.1055/s-0041-1740532","DOIUrl":"https://doi.org/10.1055/s-0041-1740532","url":null,"abstract":"<p><p>Congenital nonsyndromic hearing loss (NSHL) has been considered as one of the most prevalent chronic disorder in children. It affects the physical and mental conditions of a large children population worldwide. Because of the genetic heterogeneity, the identification of target gene is very challenging. However, gap junction β-2 ( <i>GJB2</i> ) is taken as the key gene for hearing loss, as its involvement has been reported frequently in NSHL cases. This study aimed to identify the association of <i>GJB2</i> mutants in different Indian populations based on published studies in Indian population. This will provide clear genetic fundamental of NSHL in Indian biogeography, which would be helpful in the diagnosis process.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"11 1","pages":"5-14"},"PeriodicalIF":0.4,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8847051/pdf/10-1055-s-0041-1740532.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10340043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Contributing Reviewers of 2021.","authors":"","doi":"10.1055/s-0042-1744018","DOIUrl":"https://doi.org/10.1055/s-0042-1744018","url":null,"abstract":"","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"11 1","pages":"i-iv"},"PeriodicalIF":0.4,"publicationDate":"2022-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8847057/pdf/10-1055-s-0042-1744018.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10738783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The 4q deletion syndrome is an uncommon condition manifesting with broad clinical expression and phenotypic variability. We report a 5-year-old boy affected by 4q deletion syndrome who showed minor craniofacial features, growth failure, mild developmental delay, severe speech delay, and marked irascibility and aggressivity. Moreover, he showed precocious and crowded primary dentition, digital hyperlaxity, and congenital bilateral adducted thumbs, signs which were previously unreported in the syndrome. The array comparative genomic hybridization analysis revealed a 4q partial terminal deletion of ∼329.6 kb extending from 164.703.186 to 165.032.803 nt, which includes part of MARCH1 (membrane associated ring-CH-type finger 1) gene (OMIM#613331). Same rearrangement was found in his healthy mother. Clinical phenotype of the child and its relationship to the deleted region is presented with a revision of the cases having the same copy number losses from the literature and genomic variant databases.
{"title":"A Novel 4q32.3 Deletion in a Child: Additional Signs and the Role of <i>MARCH1</i>.","authors":"Xena Giada Pappalardo, Martino Ruggieri, Raffaele Falsaperla, Salvatore Savasta, Umberto Raucci, Piero Pavone","doi":"10.1055/s-0041-1736458","DOIUrl":"https://doi.org/10.1055/s-0041-1736458","url":null,"abstract":"<p><p>The 4q deletion syndrome is an uncommon condition manifesting with broad clinical expression and phenotypic variability. We report a 5-year-old boy affected by 4q deletion syndrome who showed minor craniofacial features, growth failure, mild developmental delay, severe speech delay, and marked irascibility and aggressivity. Moreover, he showed precocious and crowded primary dentition, digital hyperlaxity, and congenital bilateral adducted thumbs, signs which were previously unreported in the syndrome. The array comparative genomic hybridization analysis revealed a 4q partial terminal deletion of ∼329.6 kb extending from 164.703.186 to 165.032.803 nt, which includes part of <i>MARCH1</i> (membrane associated ring-CH-type finger 1) gene (OMIM#613331). Same rearrangement was found in his healthy mother. Clinical phenotype of the child and its relationship to the deleted region is presented with a revision of the cases having the same copy number losses from the literature and genomic variant databases.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"10 4","pages":"259-265"},"PeriodicalIF":0.4,"publicationDate":"2021-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8608485/pdf/10-1055-s-0041-1736458.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39683519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-09-01Epub Date: 2021-07-10DOI: 10.1055/s-0041-1731036
Raffaele Falsaperla, Valentina Giacchi, Maria Giovanna Aguglia, Janette Mailo, Maria Grazia Longo, Federica Natacci, Martino Ruggieri
Congenital heart disease (CHD), the most common major congenital anomaly, is associated with a genetic syndrome (chromosomal anomalies, genomic disorders, or monogenic disease) in 30% of patients. The aim of this systematic review was to evaluate if, in the neonatal setting, clinical clues that orient the diagnostic path can be identified. For this purpose, we revised the most frequent dysmorphic features described in newborns with CHD, comparing those associated with monogenic syndromes (MSG) with the ones reported in newborns with genomic disorders. For this systematic review according to PRISMA statement, we used PubMed, Medline, Google Scholar, Scopus database, and search terms related to CHD and syndrome. We found a wide range of dysmorphisms (ocular region, ears, mouth, and/or palate and phalangeal anomalies) detected in more than half of MSGs were found to be associated with CHDs, but those anomalies are also described in genomic rearrangements syndromes with equal prevalence. These findings confirmed that etiological diagnosis in newborns is challenging, and only the prompt and expert recognition of features suggestive of genetic conditions can improve the selection of appropriate, cost-effective diagnostic tests. However, in general practice, it is crucial to recognize clues that can suggest the presence of a genetic syndrome, and neonatologists often have the unique opportunity to be the first to identify abnormalities in the neonate.
先天性心脏病(CHD)是最常见的主要先天性异常,在30%的患者中与遗传综合征(染色体异常、基因组疾病或单基因疾病)相关。本系统综述的目的是评估是否,在新生儿设置,临床线索,定向诊断路径可以确定。为此,我们修订了冠心病新生儿中最常见的畸形特征,将与单基因综合征(MSG)相关的畸形特征与基因组疾病新生儿中报道的畸形特征进行了比较。根据PRISMA声明,我们使用PubMed, Medline, Google Scholar, Scopus数据库,检索与冠心病及其综合征相关的关键词。我们发现,在半数以上的msg中检测到的广泛的畸形(眼区、耳区、嘴区和/或腭区和指骨异常)被发现与冠心病有关,但这些异常也被描述为同样普遍的基因组重排综合征。这些发现证实,新生儿的病因诊断是具有挑战性的,只有及时和专家识别暗示遗传条件的特征,才能改善选择适当的、具有成本效益的诊断测试。然而,在一般实践中,识别遗传综合征存在的线索是至关重要的,新生儿科医生通常有独特的机会第一个发现新生儿的异常。
{"title":"Monogenic Syndromes with Congenital Heart Diseases in Newborns (Diagnostic Clues for Neonatologists): A Critical Analysis with Systematic Literature Review.","authors":"Raffaele Falsaperla, Valentina Giacchi, Maria Giovanna Aguglia, Janette Mailo, Maria Grazia Longo, Federica Natacci, Martino Ruggieri","doi":"10.1055/s-0041-1731036","DOIUrl":"https://doi.org/10.1055/s-0041-1731036","url":null,"abstract":"<p><p>Congenital heart disease (CHD), the most common major congenital anomaly, is associated with a genetic syndrome (chromosomal anomalies, genomic disorders, or monogenic disease) in 30% of patients. The aim of this systematic review was to evaluate if, in the neonatal setting, clinical clues that orient the diagnostic path can be identified. For this purpose, we revised the most frequent dysmorphic features described in newborns with CHD, comparing those associated with monogenic syndromes (MSG) with the ones reported in newborns with genomic disorders. For this systematic review according to PRISMA statement, we used PubMed, Medline, Google Scholar, Scopus database, and search terms related to CHD and syndrome. We found a wide range of dysmorphisms (ocular region, ears, mouth, and/or palate and phalangeal anomalies) detected in more than half of MSGs were found to be associated with CHDs, but those anomalies are also described in genomic rearrangements syndromes with equal prevalence. These findings confirmed that etiological diagnosis in newborns is challenging, and only the prompt and expert recognition of features suggestive of genetic conditions can improve the selection of appropriate, cost-effective diagnostic tests. However, in general practice, it is crucial to recognize clues that can suggest the presence of a genetic syndrome, and neonatologists often have the unique opportunity to be the first to identify abnormalities in the neonate.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"10 3","pages":"173-193"},"PeriodicalIF":0.4,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416220/pdf/10-1055-s-0041-1731036.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39403467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}