Bhanudeep Singanamalla, Pradip Paria, Renu Suthar, Arushi G Saini, Savita V Attri
Glutaric aciduria type 1 (GA-1) is a treatable inborn error of metabolism caused by glutaryl-CoA dehydrogenase deficiency. This enzyme deficiency leads to accumulation of glutaric acid, 3-hydroxy glutaric acid, and glutaconic acid which are potentially neurotoxic. Patients with GA-1 have characteristic clinical and neuroimaging features that help us to clinch the diagnosis. Early diagnosis by newborn screening helps us to prevent the motor problems such as dystonia and spasticity. Treatment includes low-protein diet along with carnitine supplementation which may lead to deficiency of essential amino acids and hence malnutrition. Managing malnutrition in a child with inborn errors of metabolism (IEM) is challenging. Here, we describe a patient, a case of GA-1 on medical food, presenting with severe acute malnutrition, who improved with a combination of medical and home-made foods along with lysine-free, tryptophan-reduced amino acid supplements.
{"title":"The Challenge of Severe Acute Malnutrition in Inborn Errors of Metabolism: Does Medical Food Alone Suffice?","authors":"Bhanudeep Singanamalla, Pradip Paria, Renu Suthar, Arushi G Saini, Savita V Attri","doi":"10.1055/s-0041-1739288","DOIUrl":"https://doi.org/10.1055/s-0041-1739288","url":null,"abstract":"<p><p>Glutaric aciduria type 1 (GA-1) is a treatable inborn error of metabolism caused by glutaryl-CoA dehydrogenase deficiency. This enzyme deficiency leads to accumulation of glutaric acid, 3-hydroxy glutaric acid, and glutaconic acid which are potentially neurotoxic. Patients with GA-1 have characteristic clinical and neuroimaging features that help us to clinch the diagnosis. Early diagnosis by newborn screening helps us to prevent the motor problems such as dystonia and spasticity. Treatment includes low-protein diet along with carnitine supplementation which may lead to deficiency of essential amino acids and hence malnutrition. Managing malnutrition in a child with inborn errors of metabolism (IEM) is challenging. Here, we describe a patient, a case of GA-1 on medical food, presenting with severe acute malnutrition, who improved with a combination of medical and home-made foods along with lysine-free, tryptophan-reduced amino acid supplements.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"12 2","pages":"175-178"},"PeriodicalIF":0.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10118697/pdf/10-1055-s-0041-1739288.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9418880","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}
Jacinta Fonseca, C Melo, C Ferreira, M Sampaio, R Sousa, M Leão
Early infantile epileptic encephalopathy-64 (EIEE 64), also called RHOBTB2-related developmental and epileptic encephalopathy (DEE), is caused by heterozygous pathogenic variants (EIEE 64; MIM#618004) in the Rho-related BTB domain-containing protein 2 ( RHOBTB2 ) gene. To date, only 13 cases with RHOBTB2-related DEE have been reported. We add to the literature the 14th case of EIEE 64, identified by whole exome sequencing, caused by a heterozygous pathogenic variant in RHOBTB2 (c.1531C > T), p.Arg511Trp. This additional case supports the main features of RHOBTB2-related DEE: infantile-onset seizures, severe intellectual disability, impaired motor functions, postnatal microcephaly, recurrent status epilepticus, and hemiparesis after seizures.
{"title":"RHOBTB2 p.Arg511Trp Mutation in Early Infantile Epileptic Encephalopathy-64: Review and Case Report.","authors":"Jacinta Fonseca, C Melo, C Ferreira, M Sampaio, R Sousa, M Leão","doi":"10.1055/s-0040-1722288","DOIUrl":"https://doi.org/10.1055/s-0040-1722288","url":null,"abstract":"<p><p>Early infantile epileptic encephalopathy-64 (EIEE 64), also called RHOBTB2-related developmental and epileptic encephalopathy (DEE), is caused by heterozygous pathogenic variants (EIEE 64; MIM#618004) in the Rho-related BTB domain-containing protein 2 ( <i>RHOBTB2</i> ) gene. To date, only 13 cases with RHOBTB2-related DEE have been reported. We add to the literature the 14th case of EIEE 64, identified by whole exome sequencing, caused by a heterozygous pathogenic variant in RHOBTB2 (c.1531C > T), p.Arg511Trp. This additional case supports the main features of RHOBTB2-related DEE: infantile-onset seizures, severe intellectual disability, impaired motor functions, postnatal microcephaly, recurrent status epilepticus, and hemiparesis after seizures.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"12 2","pages":"155-158"},"PeriodicalIF":0.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10118705/pdf/10-1055-s-0040-1722288.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9741618","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}
Manisha Goyal, Mohammed Faruq, Ashok Gupta, Divya Shrivastava, Uzma Shamim
Hypotonia is a symptom of diminished tone of skeletal muscle and can be nongenetic or a part of genetic syndrome. Hypotonia, developmental delay, and facial dysmorphism are nonspecific findings observed in many genetic syndromes mostly in chromosomal microdeletion and duplication. Here we report a case with severe hypotonia and facial dysmorphism, diagnosed with deletion at 6q13q14.3 by array comparative genomic hybridization (CGH) at very early age. Recent genetic diagnostic technologies such as array CGH may enable clinicians to diagnose chromosomal abnormalities earlier and provide appropriate medical management.
{"title":"6q13q14.3 Microdeletion Syndrome with Severe Hypotonia and Facial Dysmorphism: Genotype-Phenotype Correlation.","authors":"Manisha Goyal, Mohammed Faruq, Ashok Gupta, Divya Shrivastava, Uzma Shamim","doi":"10.1055/s-0040-1721739","DOIUrl":"https://doi.org/10.1055/s-0040-1721739","url":null,"abstract":"<p><p>Hypotonia is a symptom of diminished tone of skeletal muscle and can be nongenetic or a part of genetic syndrome. Hypotonia, developmental delay, and facial dysmorphism are nonspecific findings observed in many genetic syndromes mostly in chromosomal microdeletion and duplication. Here we report a case with severe hypotonia and facial dysmorphism, diagnosed with deletion at 6q13q14.3 by array comparative genomic hybridization (CGH) at very early age. Recent genetic diagnostic technologies such as array CGH may enable clinicians to diagnose chromosomal abnormalities earlier and provide appropriate medical management.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"12 2","pages":"141-143"},"PeriodicalIF":0.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10118712/pdf/10-1055-s-0040-1721739.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9741619","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}
Juan Jose Nieto-Barcelo, Noelia Gonzalez Montes, Isabel Gonzalo Alonso, Francisco Martinez, Maria Jose Aparisi, Marina Martinez-Matilla, Ana Victoria Marco Hernandez, Miguel Tomás Vila
Mutations in SCN2A genes have been described in patients with epilepsy, finding a large phenotypic variability, from benign familial epilepsy to epileptic encephalopathy. To explain this variability, it was proposed the existence of dominant modifier alleles at one or more loci that contribute to determine the severity of the epilepsy phenotype. One example of modifier factor may be the CACNA1G gene, as proved in animal models. We present a 6-day-old male newborn with recurrent seizures in which a mutation in the SCN2A gene is observed, in addition to a variant in CACNA1G gene. Our patient suffered in the first days of life myoclonic seizures, with pathologic intercritical electroencephalogram pattern, requiring multiple drugs to achieve adequate control of them. During the next weeks, the patient progressively improved until complete remission at the second month of life, being possible to withdraw the antiepileptic treatment. We propose that the variant in CACNA1G gene could have acted as a modifier of the epilepsy syndrome produced by the mutation in SCN2A gene in our patient.
{"title":"Variant in <i>CACNA1G</i> as a Possible Genetic Modifier of Neonatal Epilepsy in an Infant with a De Novo <i>SCN2A</i> Mutation.","authors":"Juan Jose Nieto-Barcelo, Noelia Gonzalez Montes, Isabel Gonzalo Alonso, Francisco Martinez, Maria Jose Aparisi, Marina Martinez-Matilla, Ana Victoria Marco Hernandez, Miguel Tomás Vila","doi":"10.1055/s-0041-1723958","DOIUrl":"https://doi.org/10.1055/s-0041-1723958","url":null,"abstract":"<p><p>Mutations in <i>SCN2A</i> genes have been described in patients with epilepsy, finding a large phenotypic variability, from benign familial epilepsy to epileptic encephalopathy. To explain this variability, it was proposed the existence of dominant modifier alleles at one or more loci that contribute to determine the severity of the epilepsy phenotype. One example of modifier factor may be the <i>CACNA1G</i> gene, as proved in animal models. We present a 6-day-old male newborn with recurrent seizures in which a mutation in the <i>SCN2A</i> gene is observed, in addition to a variant in <i>CACNA1G</i> gene. Our patient suffered in the first days of life myoclonic seizures, with pathologic intercritical electroencephalogram pattern, requiring multiple drugs to achieve adequate control of them. During the next weeks, the patient progressively improved until complete remission at the second month of life, being possible to withdraw the antiepileptic treatment. We propose that the variant in <i>CACNA1G</i> gene could have acted as a modifier of the epilepsy syndrome produced by the mutation in <i>SCN2A</i> gene in our patient.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"12 2","pages":"159-162"},"PeriodicalIF":0.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10118702/pdf/10-1055-s-0041-1723958.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9756695","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}
Sickle cell anemia (SCA) is a severe disease characterized by anemia, acute clinical complications, and a relatively short life span. In this disease, abnormal hemoglobin makes the red blood cells deformed, rigid, and sticky. Fetal hemoglobin (HbF) is one of the key modulators of SCA morbidity and mortality. Interindividual HbF variation is a heritable trait that is controlled by polymorphism in genes linked and unlinked to the hemoglobin β gene (HBB). The genetic polymorphisms that determine HbF levels are known to ameliorate acute clinical events. About 190 well-characterized homozygous SCA patients were included in this study. Complete blood count (CBC), high-performance liquid chromatography (HPLC), and clinical investigations were obtained from patient's records. Severity scores were determined by using the combination of anemia, complications, total leucocyte count, and transfusion scores. HBG2 rs7482144 polymorphism was genotyped by using the polymerase chain reaction and restriction fragment length polymorphism. The association between HBG2 rs7482144 polymorphism and HbF levels as well as the disease severity of SCA were assessed. SCA patients carrying TT genotype were found to have higher HbF levels. In addition, SCA patients with increased severity showed significantly lower levels of hemoglobin, HbF, and hematocrit values. However, the genotypes of HBG2 rs7482144 polymorphism were not found to be associated with the risk of disease severity. In summary, this study demonstrated that HBG2 rs7482144 polymorphism is linked with HbF levels, but it does not affect disease severity. The sample sizes used and the pattern of association deduced from our small sample size prevents us from extrapolating our findings further.
{"title":"The <i>HBG2</i> rs7482144 (C > T) Polymorphism is Linked to HbF Levels but not to the Severity of Sickle Cell Anemia.","authors":"Bhaskar V K S Lakkakula, Smaranika Pattnaik","doi":"10.1055/s-0041-1733950","DOIUrl":"https://doi.org/10.1055/s-0041-1733950","url":null,"abstract":"<p><p>Sickle cell anemia (SCA) is a severe disease characterized by anemia, acute clinical complications, and a relatively short life span. In this disease, abnormal hemoglobin makes the red blood cells deformed, rigid, and sticky. Fetal hemoglobin (HbF) is one of the key modulators of SCA morbidity and mortality. Interindividual HbF variation is a heritable trait that is controlled by polymorphism in genes linked and unlinked to the hemoglobin β gene (HBB). The genetic polymorphisms that determine HbF levels are known to ameliorate acute clinical events. About 190 well-characterized homozygous SCA patients were included in this study. Complete blood count (CBC), high-performance liquid chromatography (HPLC), and clinical investigations were obtained from patient's records. Severity scores were determined by using the combination of anemia, complications, total leucocyte count, and transfusion scores. <i>HBG2</i> rs7482144 polymorphism was genotyped by using the polymerase chain reaction and restriction fragment length polymorphism. The association between <i>HBG2</i> rs7482144 polymorphism and HbF levels as well as the disease severity of SCA were assessed. SCA patients carrying TT genotype were found to have higher HbF levels. In addition, SCA patients with increased severity showed significantly lower levels of hemoglobin, HbF, and hematocrit values. However, the genotypes of <i>HBG2</i> rs7482144 polymorphism were not found to be associated with the risk of disease severity. In summary, this study demonstrated that <i>HBG2</i> rs7482144 polymorphism is linked with HbF levels, but it does not affect disease severity. The sample sizes used and the pattern of association deduced from our small sample size prevents us from extrapolating our findings further.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"12 2","pages":"129-134"},"PeriodicalIF":0.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10118708/pdf/10-1055-s-0041-1733950.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9756697","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}
Daniel R Carvalho, Carlos E Speck-Martins, Bernardo J A F Martins, Ana Paula Izumi, Alessandra La Rocque-Ferreira
Acute necrotizing encephalopathy (ANE) is clinically characterized by fever, acute alteration of consciousness, seizures, and rapid progression to coma within days of onset of a viral illness occurring in healthy children without evidence of central nervous system infection. Brain magnetic resonance imaging (MRI) shows multiple symmetrical lesions affecting primarily the thalami but also brain stem, putamina, periventricular white matter, and cerebellum. Most cases of ANE are sporadic and nonrecurrent. However, a missense variant in RANBP2 has been identified in some families with recurrent ANE (OMIM # 608033), also named autosomal dominant ANE (ADANE). Clinical manifestation, clinical course, and brain MRI imaging findings of six affected members of two distinct families with ADANE were described. Sequencing revealed heterozygous c.1754C > T variant in RANBP2 (p.Thr585Met) in affected and asymptomatic family members. Only few ADANE families have been reported and it is the first description in South America. Differential diagnosis of Leigh disease and acute disseminated encephalomyelitis is discussed. Our report reinforces incomplete penetrance of ADANE and intrafamilial phenotypic variability of outcome.
{"title":"Variable Presentation and Reduced Penetrance in Autosomal Dominant Acute Necrotizing Encephalopathy Related to RANBP2 Variant.","authors":"Daniel R Carvalho, Carlos E Speck-Martins, Bernardo J A F Martins, Ana Paula Izumi, Alessandra La Rocque-Ferreira","doi":"10.1055/s-0040-1721802","DOIUrl":"https://doi.org/10.1055/s-0040-1721802","url":null,"abstract":"<p><p>Acute necrotizing encephalopathy (ANE) is clinically characterized by fever, acute alteration of consciousness, seizures, and rapid progression to coma within days of onset of a viral illness occurring in healthy children without evidence of central nervous system infection. Brain magnetic resonance imaging (MRI) shows multiple symmetrical lesions affecting primarily the thalami but also brain stem, putamina, periventricular white matter, and cerebellum. Most cases of ANE are sporadic and nonrecurrent. However, a missense variant in RANBP2 has been identified in some families with recurrent ANE (OMIM # 608033), also named autosomal dominant ANE (ADANE). Clinical manifestation, clinical course, and brain MRI imaging findings of six affected members of two distinct families with ADANE were described. Sequencing revealed heterozygous c.1754C > T variant in RANBP2 (p.Thr585Met) in affected and asymptomatic family members. Only few ADANE families have been reported and it is the first description in South America. Differential diagnosis of Leigh disease and acute disseminated encephalomyelitis is discussed. Our report reinforces incomplete penetrance of ADANE and intrafamilial phenotypic variability of outcome.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"12 2","pages":"144-149"},"PeriodicalIF":0.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10118696/pdf/10-1055-s-0040-1721802.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9444846","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}
Juvenile open-angle glaucoma (JOAG) is an uncommon subset of primary glaucoma with an onset before the age of 40 years. In this case report, we describe the cosegregation of MYOC , p.Pro370Leu and LTBP2 , p.Pro432Leu mutations in a family with JOAG. The family with autosomal dominant JOAG belonged to Northern India. The samples of proband and her parents were evaluated by whole exome sequencing. Sanger sequencing was conducted in all the study participants to check the mutations identified. Both MYOC and LTBP2 mutations were found to cosegregate in affected individuals leading to a severe JOAG phenotype, thereby suggesting a digenic inheritance of MYOC with LTBP2 in this family.
{"title":"Digenic Inheritance in Juvenile Open-Angle Glaucoma.","authors":"Bindu I Somarajan, Shikha Gupta, Karthikeyan Mahalingam, Kishan Azmira, Viney Gupta","doi":"10.1055/s-0040-1722213","DOIUrl":"https://doi.org/10.1055/s-0040-1722213","url":null,"abstract":"<p><p>Juvenile open-angle glaucoma (JOAG) is an uncommon subset of primary glaucoma with an onset before the age of 40 years. In this case report, we describe the cosegregation of <i>MYOC</i> , p.Pro370Leu and <i>LTBP2</i> , p.Pro432Leu mutations in a family with JOAG. The family with autosomal dominant JOAG belonged to Northern India. The samples of proband and her parents were evaluated by whole exome sequencing. Sanger sequencing was conducted in all the study participants to check the mutations identified. Both <i>MYOC</i> and <i>LTBP2</i> mutations were found to cosegregate in affected individuals leading to a severe JOAG phenotype, thereby suggesting a digenic inheritance of <i>MYOC</i> with <i>LTBP2</i> in this family.</p>","PeriodicalId":16695,"journal":{"name":"Journal of pediatric genetics","volume":"12 2","pages":"150-154"},"PeriodicalIF":0.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10118699/pdf/10-1055-s-0040-1722213.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9444847","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}
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.
使用瞳距(IPD)的客观评价眼远视和低远视是推荐确证综合征的诊断条件。鉴于完全缺乏关于IPD生长的系列数据,本研究旨在揭示印度裔唐氏综合症(DS)儿童IPD的生理动力学。在研究所生长实验室/生长诊所使用“数字滑动卡尺”每隔6个月测量1,125名0 - 3个月至10岁的DS儿童(男752人,女373人)的内眦距离(ICD)和外眦距离(OCD)。采用Feingold and Bossert(1974)公式,通过测量男性和女性DS儿童的ICD和OCD来计算各年龄段的IPD。像强迫症和ICD一样,IPD在残疾儿童中不断增加。此后5年IPD快速增长,增速有所放缓。一般来说,男孩比女孩拥有更大的IPD,然而,性别差异在4岁前变得具有统计学意义。与正常的印度儿童相比,我们的研究儿童具有明显较小的IPD。在我们的DS患儿中,没有一例出现远视,而在4.9%的男性和16.8%的女性DS患者中出现了远视。与标准IPD数据的比较无法确定DS患儿是否存在远视(
{"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, Harvinder Kaur, Rupinder Kaur, Inusha Panigrahi, 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":"12 2","pages":"123-128"},"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}
Dipika Menon, John N Dentel, Yamuna Sanil, David Lawrence
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.
{"title":"Cardiac Fibroma with Asymptomatic Ventricular Arrhythmia in an Adolescent with Gorlin's Syndrome.","authors":"Dipika Menon, John N Dentel, Yamuna Sanil, 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":"12 2","pages":"171-174"},"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}
Pub Date : 2023-05-11eCollection Date: 2023-09-01DOI: 10.1055/s-0043-1768693
Nejmiye Akkuş, Tuğba Akın Duman
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.
{"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":"12 3","pages":"193-198"},"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}