Journal of pediatric genetics最新文献

{"title":"Cardiac Fibroma with Asymptomatic Ventricular Arrhythmia in an Adolescent with Gorlin's Syndrome.","authors":"Dipika Menon,&nbsp;John N Dentel,&nbsp;Yamuna Sanil,&nbsp;David Lawrence","doi":"10.1055/s-0040-1722287","DOIUrl":"https://doi.org/10.1055/s-0040-1722287","url":null,"abstract":"<p><p>Nevoid basal cell carcinoma syndrome (NBCCS), also referred to as Gorlin's syndrome, is an autosomal dominant inherited condition that predisposes affected individuals to various tumors such as cardiac fibromas. Though technically benign, cardiac fibromas may result in malignant arrhythmias and sudden death. The pertinent literature pertaining to pediatric cases of cardiac fibromas and their clinical features were reviewed. We present the case of an asymptomatic teenage with de novo NBCCS who was diagnosed with both NBCCS and cardiac fibroma later in life. The patient was noted to have clinically significant ventricular arrhythmias that were eliminated with tumor resection. There are no established best practice guidelines for the management of cardiac fibromas in patients with NBCCS. Given the risk of sudden arrhythmic death, the presence of ventricular arrhythmias should prompt strong consideration of tumor resection.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":null,"pages":null},"PeriodicalIF":0.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10118701/pdf/10-1055-s-0040-1722287.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9388942","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":"Growth Pattern and Use of Inter-pupillary Distance in the Detection of Ocular Hypertelorism and Hypotelorism in Indian Down Syndrome Children.","authors":"Anil Kumar Bhalla,&nbsp;Harvinder Kaur,&nbsp;Rupinder Kaur,&nbsp;Inusha Panigrahi,&nbsp;Brij Nandan Singh Walia","doi":"10.1055/s-0041-1736612","DOIUrl":"https://doi.org/10.1055/s-0041-1736612","url":null,"abstract":"<p><p>Use of inter-pupillary distance (IPD) for objective evaluation of ocular hypertelorism and hypotelorism is recommended to corroborate diagnosis of syndromic conditions. In view of complete absence of serial data on growth of IPD, this study aims to unfold auxological dynamics of IPD in Down syndrome (DS) children of Indian origin. Inner canthal distance (ICD) and outer canthal distance (OCD) were measured on a total of 1,125 (male: 752, female: 373) DS children, aged 0 to 3 months to 10 years at 6 monthly age intervals using a \"Digimatic Sliding Caliper\" in the Growth Laboratory/Growth Clinic of the Institute. Using Feingold and Bossert (1974) formula, IPD at each age was calculated from ICD and OCD measured among male and female DS children. IPD, like OCD and ICD increased un-interruptedly among DS children. IPD grew rapidly up to 5 years thereafter, its rapidity became slower. Boys in general, possessed larger IPD than girls, however, gender differences became statistically significant up to first 4 years of life. Our study children possessed significantly smaller IPD as compared with their normal Indian counterparts. None of our DS children depicted ocular hypertelorism while hypotelorism, was noticed amongst 4.9% male and 16.8% female DS patients. Comparison with normative IPD data failed to establish existence of ocular hypertelorism in DS children (<10 years) of north-western Indian origin. Use of age and gender-specific data presented for IPD of DS children may be made for comparative purpose to ascertain inter-population variability.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":null,"pages":null},"PeriodicalIF":0.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10118700/pdf/10-1055-s-0041-1736612.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9741626","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":"First Clinical Report of Two <i>RAB3GAP1</i> Pathogenic Variant in Warburg Micro Syndrome.","authors":"Nejmiye Akkuş, Tuğba Akın Duman","doi":"10.1055/s-0043-1768693","DOIUrl":"10.1055/s-0043-1768693","url":null,"abstract":"<p><p>Warburg micro (WARBM) syndrome is an autosomal recessive disease characterized by severe brain and eye abnormalities. Loss-of-function mutations in RAB18, RAB3GAP2, RAB3GAP1, or TBC1D20 can lead to this disease. Here, we present two unrelated WARBM syndrome patients who had an RAB3GAP1 c.559 C > T, (p.Arg187Ter) and c.520 C > T (p.Arg174Ter) homozygous state. Both patients had microcephaly, microphthalmia, microcornea, bilateral congenital cataracts, severe intellectual disability, and congenital hypotonia. Using the method of next-generation sequencing and sanger sequencing, we found two nonsense variations at the splice site in exon 7 of RAB3GAP1 in the WARBM syndrome patients. The mutations were predicted to cause the syndrome due to the early stop codon, and the patients had the WARBM1 syndrome. We present the first clinical report of two different unreported variants with RAB3GAP1 mutation in the literature.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":null,"pages":null},"PeriodicalIF":0.4,"publicationDate":"2023-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10421685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9995771","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":"<i>FOXP1</i> Haploinsufficiency Contributes to the Development of Congenital Diaphragmatic Hernia.","authors":"Katherine E Pendleton, Andres Hernandez-Garcia, Jennifer M Lyu, Ian M Campbell, Chad A Shaw, Julie Vogt, Frances A High, Patricia K Donahoe, Wendy K Chung, Daryl A Scott","doi":"10.1055/s-0043-1767731","DOIUrl":"10.1055/s-0043-1767731","url":null,"abstract":"<p><p><i>FOXP1</i> encodes a transcription factor involved in tissue regulation and cell-type-specific functions. Haploinsufficiency of <i>FOXP1</i> is associated with a neurodevelopmental disorder: autosomal dominant mental retardation with language impairment with or without autistic features. More recently, heterozygous <i>FOXP1</i> variants have also been shown to cause a variety of structural birth defects including central nervous system (CNS) anomalies, congenital heart defects, congenital anomalies of the kidney and urinary tract, cryptorchidism, and hypospadias. In this report, we present a previously unpublished case of an individual with congenital diaphragmatic hernia (CDH) who carries an approximately 3.8 Mb deletion. Based on this deletion, and deletions previously reported in two other individuals with CDH, we define a CDH critical region on chromosome 3p13 that includes <i>FOXP1</i> and four other protein-coding genes. We also provide detailed clinical descriptions of two previously reported individuals with CDH who carry de novo, pathogenic variants in <i>FOXP1</i> that are predicted to trigger nonsense-mediated mRNA decay. A subset of individuals with putatively deleterious <i>FOXP4</i> variants has also been shown to develop CDH. Since FOXP proteins function as homo- or heterodimers and the homologs of <i>FOXP1</i> and <i>FOXP4</i> are expressed at the same time points in the embryonic mouse diaphragm, they may function together as a dimer, or in parallel as homodimers, to regulate gene expression during diaphragm development. Not all individuals with heterozygous, loss-of-function changes in <i>FOXP1</i> develop CDH. Hence, we conclude that <i>FOXP1</i> acts as a susceptibility factor that contributes to the development of CDH in conjunction with other genetic, epigenetic, environmental, and/or stochastic factors.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":null,"pages":null},"PeriodicalIF":0.4,"publicationDate":"2023-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10984716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88458636","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":"A Brief View of The Prophet Ayyub's (Alayhi As-Salam) Disease: Was It Job's Syndrome?","authors":"Hüseyin Çaksen","doi":"10.1055/s-0043-1764300","DOIUrl":"10.1055/s-0043-1764300","url":null,"abstract":"","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":null,"pages":null},"PeriodicalIF":0.4,"publicationDate":"2023-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10421672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9995778","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":"Cohort of Phenotype, Genotype, and Outcome of <i>SCN</i> Developmental and Epileptic Encephalopathies from Southern Part of India.","authors":"Vykuntaraju K Gowda,&nbsp;Manojna Battina,&nbsp;Hemadri Vegda,&nbsp;Varunvenkat M Srinivasan,&nbsp;Surendra K Chikara,&nbsp;Adrija Mishra,&nbsp;Sanjay K Shivappa,&nbsp;Naveen Benakappa","doi":"10.1055/s-0041-1731020","DOIUrl":"https://doi.org/10.1055/s-0041-1731020","url":null,"abstract":"<p><p>The <i>SCN</i> encephalopathies are one of the rare early childhood intractable epileptic encephalopathies associated with pleomorphic seizures, cognitive decline, motor, and behavioral abnormalities that begin in early infancy. There is a dearth of data on phenotype and genotype of <i>SCN</i> encephalopathies from the Indian subcontinent, hence we are reporting clinical and molecular profile and outcome of <i>SCN</i> developmental and epileptic encephalopathies. This is a retrospective chart review of <i>SCN</i> developmental and epileptic encephalopathies in a tertiary care center, Bangalore, India between January 2015 and March 2020. All children with clinical features of <i>SCN</i> developmental and epileptic encephalopathies and confirmed with pathogenic variants were included. A total of 50 cases of <i>SCN</i> developmental and epileptic encephalopathies were analyzed, 31 of them were male and the mean age of presentation was 7.8 months. Precipitating factors for the first episode of seizure were fever and vaccination accounting for 33 and 8 children, respectively. Forty (80%) children had prolonged seizures and 15 (30%) had epileptic spasms. All children had a normal birth history and normal development before the onset of seizures, which was followed by developmental delay and regression. Thirty (60%) children had behavioral difficulties, notable hyperactivity, and autistic features. Neuroimaging and the initial electroencephalogram (EEG) were normal in all patients. The mean age of abnormal EEG was 14 months. The various subtypes of <i>SCN</i> variants were <i>SCN1A</i> in 31 children followed by <i>SCN2A</i> and <i>SCN9A</i> in eight children each and <i>SCN1B</i> in three children. Frameshift and nonsense mutations were associated with more severe phenotype and poor outcome compared with missense mutations. Thirty-four patients partially responded to treatment and the rest were refractory. The results of genetic testing were used to guide treatment; sodium channel blocking antiepileptic drugs were discontinued in 15 patients and sodium channel blocking agents were started in 3 patients with partial response. Three out of four children on stiripentol had a partial response. The <i>SCN</i> developmental and epileptic encephalopathies can present with epileptic spasms in addition to other types of seizures. Epileptic spasms are more common in nonsense and frameshift mutations. The outcome is poor in children with epileptic spasms compared with those without epileptic spasms. Genetic testing helps to select antiepileptic drugs that lead to seizure reduction.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":null,"pages":null},"PeriodicalIF":0.4,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9848768/pdf/10-1055-s-0041-1731020.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9146577","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":"Erratum: Erratum: <i>KCNQ2</i> Encephalopathy and Responsiveness to Pyridoxal-5'-Phosphate.","authors":"Chit Kwong Chow,&nbsp;Ho Ming Luk,&nbsp;Suet Na Wong","doi":"10.1055/s-0041-1735896","DOIUrl":"https://doi.org/10.1055/s-0041-1735896","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1055/s-0040-1721384.].</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":null,"pages":null},"PeriodicalIF":0.4,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9848753/pdf/10-1055-s-0041-1735896.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10662173","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":"Genetic Defects in Children with Cardiac Anomalies/Malformations: Noonan and CFC Syndromes.","authors":"Divya Kumari,&nbsp;Deepti Chaudhary,&nbsp;Inusha Panigrahi,&nbsp;Manoj K Rohit","doi":"10.1055/s-0040-1721441","DOIUrl":"https://doi.org/10.1055/s-0040-1721441","url":null,"abstract":"<p><p>Cardiac defects presenting in childhood show significant phenotypic and genetic heterogeneity. With availability of advanced genetic technologies, these can be detected early using specialized testing. Prenatal testing is currently feasible with improved ultrasonography and fetal echocardiography. Here, we report two cases of Noonan's and cardiofaciocutaneous syndromes in patients seen in the genetic unit of a tertiary care center presenting with cardiac defect with or without developmental delay, short stature, and dysmorphism. In these conditions, there is also increased risk of malignancy such as juvenile myelomonocytic leukemia. With the advent of next-generation sequencing, definitive diagnosis and counseling is possible in this group of conditions.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":null,"pages":null},"PeriodicalIF":0.4,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9848759/pdf/10-1055-s-0040-1721441.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9146570","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":"Kindler's Syndrome with Recurrent Neutropenia: Report of Two Cases from Saudi Arabia.","authors":"Yousef Binamer,&nbsp;Muzamil A Chisti","doi":"10.1055/s-0040-1721077","DOIUrl":"https://doi.org/10.1055/s-0040-1721077","url":null,"abstract":"<p><p>Kindler syndrome (KS) is a rare photosensitivity disorder with autosomal recessive mode of inheritance. It is characterized by acral blistering in infancy and childhood, progressive poikiloderma, skin atrophy, abnormal photosensitivity, and gingival fragility. Besides these major features, many minor presentations have also been reported in the literature. We are reporting two cases with atypical features of the syndrome and a new feature of recurrent neutropenia. Whole exome sequencing analysis was done using next-generation sequencing which detected a homozygous loss-of-function (LOF) variant of <i>FERMT1</i> in both patients. The variant is classified as a pathogenic variant as per the American College of Medical Genetics and Genomics guidelines. Homozygous LOF variants of <i>FERMT1</i> are a common mechanism of KS and as such confirm the diagnosis of KS in our patients even though the presentation was atypical.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":null,"pages":null},"PeriodicalIF":0.4,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9848764/pdf/10-1055-s-0040-1721077.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10635604","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":"Homozygous Novel Variants in the Glycine Decarboxylase Gene Associated with Nonketotic Hyperglycinemia in a Distinct Population.","authors":"Heba Salah Abdelkhalek Elabd,&nbsp;Fatma Bastaki,&nbsp;Mohamed Khalifa","doi":"10.1055/s-0041-1729741","DOIUrl":"https://doi.org/10.1055/s-0041-1729741","url":null,"abstract":"<p><p>Glycine encephalopathy (GE), also known as nonketotic hyperglycinemia (NKH) is an autosomal recessive disorder due to a primary defect in the glycine cleavage enzyme system. It is characterized by elevated levels of glycine in the plasma and cerebrospinal fluid (CSF) and increased CSF to plasma glycine ratio. Mutations in three genes of the mitochondrial glycine cleavage system have been found to cause NKH. Most patients have a mutation in the <i>GLDC</i> . In this report, we present five new patients from Middle Eastern families with NKH. They were all born to consanguineous parents and two of them have family history of similarly affected sibling(s). All patients presented with neonatal encephalopathy associated with seizures. Their diagnoses were suspected clinically and confirmed biochemically. DNA sequence analysis of the five patients revealed five different pathogenic or likely pathogenic variants in the <i>GLDC</i> . Three were missense variants (c.2675C > T; p.Ala892Val), (c.2512A > G; p.Asn838Asp), and (c.2943A > C; p.Lys981Asn); one was an intronic missense variant (c.1402-2A > T) leading to an exonic deletion, and one was a deletion of 42 amino acids (c.1927-?_2052 + ?del.) All variants were novel and homozygous. The pathogenicity of these variants was determined according to the American College of Medical Genetics (ACMG) variant classification and in silico analysis. Another novel homozygous variant (c.1384C > G; p.Leu462Val) was detected, which was classified as likely benign. The novel variants identified in the <i>GLDC</i> in these patients underlie the pathogenesis of NKH, specifically for the Middle Eastern population. This expands the mutation spectrum of NKH to include a distinct ethnic population that has not been studied before.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":null,"pages":null},"PeriodicalIF":0.4,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9848757/pdf/10-1055-s-0041-1729741.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9132322","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}