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Cardiac Fibroma with Asymptomatic Ventricular Arrhythmia in an Adolescent with Gorlin's Syndrome. 青少年Gorlin综合征并发无症状室性心律失常的心脏纤维瘤。
IF 0.4 Pub Date : 2023-06-01 DOI: 10.1055/s-0040-1722287
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.

Nevoid基底细胞癌综合征(NBCCS),也被称为Gorlin综合征,是一种常染色体显性遗传疾病,使患者易患各种肿瘤,如心脏纤维瘤。虽然从技术上讲是良性的,但心脏纤维瘤可能导致恶性心律失常和猝死。本文回顾了有关小儿心脏纤维瘤病例及其临床特征的相关文献。我们提出的情况下,无症状的青少年新生NBCCS谁被诊断为NBCCS和心脏纤维瘤后来的生活。患者被注意到有临床上显著的室性心律失常,并通过肿瘤切除消除。对于NBCCS患者心脏纤维瘤的治疗,目前还没有确定的最佳实践指南。考虑到突发性心律失常死亡的风险,室性心律失常的存在应强烈考虑肿瘤切除。
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引用次数: 0
Growth Pattern and Use of Inter-pupillary Distance in the Detection of Ocular Hypertelorism and Hypotelorism in Indian Down Syndrome Children. 印度唐氏综合症儿童瞳孔间距离的生长模式和使用检测远视和低远视。
IF 0.4 Pub Date : 2023-06-01 DOI: 10.1055/s-0041-1736612
Anil Kumar Bhalla, Harvinder Kaur, Rupinder Kaur, Inusha Panigrahi, Brij Nandan Singh Walia

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(
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引用次数: 0
First Clinical Report of Two RAB3GAP1 Pathogenic Variant in Warburg Micro Syndrome. 沃伯格微综合征中两个 RAB3GAP1 致病变体的首次临床报告
IF 0.4 Pub Date : 2023-05-11 eCollection Date: 2023-09-01 DOI: 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.

沃伯格显微(WARBM)综合征是一种常染色体隐性遗传病,以严重的脑部和眼部异常为特征。RAB18、RAB3GAP2、RAB3GAP1 或 TBC1D20 的功能缺失突变可导致这种疾病。在这里,我们介绍了两名无亲属关系的 WARBM 综合征患者,他们的 RAB3GAP1 c.559 C > T(p.Arg187Ter)和 c.520 C > T(p.Arg174Ter)均为同基因状态。两名患者均患有小头畸形、小眼球症、小角膜症、双侧先天性白内障、严重智力障碍和先天性肌张力低下。通过下一代测序和桑格测序,我们在 WARBM 综合征患者的 RAB3GAP1 第 7 外显子剪接位点上发现了两个无义变异。据预测,这些突变会因早期终止密码子而导致该综合征,患者因此患上了 WARBM1 综合征。我们首次在临床上报告了文献中未报道的两种不同的RAB3GAP1变异。
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引用次数: 0
FOXP1 Haploinsufficiency Contributes to the Development of Congenital Diaphragmatic Hernia. FOXP1单倍体缺陷导致先天性膈疝的形成
IF 0.4 Q4 PEDIATRICS Pub Date : 2023-03-28 eCollection Date: 2024-03-01 DOI: 10.1055/s-0043-1767731
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

FOXP1 encodes a transcription factor involved in tissue regulation and cell-type-specific functions. Haploinsufficiency of FOXP1 is associated with a neurodevelopmental disorder: autosomal dominant mental retardation with language impairment with or without autistic features. More recently, heterozygous FOXP1 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 FOXP1 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 FOXP1 that are predicted to trigger nonsense-mediated mRNA decay. A subset of individuals with putatively deleterious FOXP4 variants has also been shown to develop CDH. Since FOXP proteins function as homo- or heterodimers and the homologs of FOXP1 and FOXP4 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 FOXP1 develop CDH. Hence, we conclude that FOXP1 acts as a susceptibility factor that contributes to the development of CDH in conjunction with other genetic, epigenetic, environmental, and/or stochastic factors.

FOXP1 是一种参与组织调节和细胞特异功能的转录因子。FOXP1 的单倍体缺陷与一种神经发育障碍有关:常染色体显性智力低下,伴有或不伴有自闭症特征的语言障碍。最近,杂合子 FOXP1 变异也被证明可导致多种结构性先天缺陷,包括中枢神经系统(CNS)异常、先天性心脏缺陷、先天性肾脏和泌尿道异常、隐睾症和尿道下裂。在本报告中,我们发现了一例之前未发表过的先天性膈疝(CDH)患者,该患者携带约 3.8 Mb 的缺失。根据这一缺失以及之前报道的另外两名 CDH 患者的缺失,我们在 3p13 染色体上定义了一个 CDH 关键区域,其中包括 FOXP1 和其他四个蛋白编码基因。我们还对之前报道的两名 CDH 患者进行了详细的临床描述,这两名患者携带 FOXP1 的新致病变异,预计会引发无义介导的 mRNA 衰减。有研究表明,一部分携带可能致癌的 FOXP4 变体的患者也会发展为 CDH。由于 FOXP 蛋白具有同源或异源二聚体的功能,而且 FOXP1 和 FOXP4 的同源物在胚胎小鼠膈肌的同一时间点表达,因此它们可能作为二聚体或作为同源二聚体在膈肌发育过程中共同调节基因表达。并非所有 FOXP1 杂合子功能缺失的个体都会患 CDH。因此,我们得出结论:FOXP1 是一种易感因素,它与其他遗传、表观遗传、环境和/或随机因素共同作用,导致 CDH 的发生。
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引用次数: 0
A Brief View of The Prophet Ayyub's (Alayhi As-Salam) Disease: Was It Job's Syndrome? 先知阿尤布(阿拉伊-阿斯-萨拉姆)的疾病简介:是约伯氏综合症吗?
IF 0.4 Q4 PEDIATRICS Pub Date : 2023-03-10 eCollection Date: 2023-09-01 DOI: 10.1055/s-0043-1764300
Hüseyin Çaksen
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引用次数: 0
Cohort of Phenotype, Genotype, and Outcome of SCN Developmental and Epileptic Encephalopathies from Southern Part of India. 印度南部SCN发育性和癫痫性脑病的表型、基因型和预后队列研究
IF 0.4 Pub Date : 2023-03-01 DOI: 10.1055/s-0041-1731020
Vykuntaraju K Gowda, Manojna Battina, Hemadri Vegda, Varunvenkat M Srinivasan, Surendra K Chikara, Adrija Mishra, Sanjay K Shivappa, Naveen Benakappa

The SCN 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 SCN encephalopathies from the Indian subcontinent, hence we are reporting clinical and molecular profile and outcome of SCN developmental and epileptic encephalopathies. This is a retrospective chart review of SCN developmental and epileptic encephalopathies in a tertiary care center, Bangalore, India between January 2015 and March 2020. All children with clinical features of SCN developmental and epileptic encephalopathies and confirmed with pathogenic variants were included. A total of 50 cases of SCN 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 SCN variants were SCN1A in 31 children followed by SCN2A and SCN9A in eight children each and SCN1B 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 SCN 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.

SCN脑病是一种罕见的早期儿童顽固性癫痫性脑病,与婴儿期早期开始的多形性癫痫发作、认知能力下降、运动和行为异常有关。由于缺乏来自印度次大陆的SCN脑病的表型和基因型数据,因此我们报告SCN发育性和癫痫性脑病的临床和分子特征和结果。这是2015年1月至2020年3月期间印度班加罗尔三级保健中心SCN发育性和癫痫性脑病的回顾性图表综述。所有具有SCN发育性和癫痫性脑病临床特征并确诊为致病变异的儿童均被纳入研究。本文分析50例SCN发育性和癫痫性脑病,其中31例为男性,平均发病年龄为7.8个月。首次发作的诱发因素为发热和接种疫苗,分别占33例和8例。40例(80%)儿童有长时间癫痫发作,15例(30%)有癫痫性痉挛。所有患儿在癫痫发作前均有正常的出生史和发育,随后出现发育迟缓和倒退。30名(60%)儿童有行为困难、明显的多动和自闭特征。所有患者的神经影像学和初始脑电图均正常。异常脑电图的平均年龄为14个月。SCN变异的各种亚型分别为:31名儿童的SCN1A, 8名儿童的SCN2A和SCN9A, 3名儿童的SCN1B。与错义突变相比,移码突变和无义突变与更严重的表型和更差的预后相关。34例患者对治疗有部分反应,其余患者难治性。基因检测结果用于指导治疗;15例患者停用钠通道阻断类抗癫痫药物,3例患者开始使用钠通道阻断类抗癫痫药物。四分之三的服用斯瑞喷妥的儿童有部分反应。SCN发育性和癫痫性脑病除了其他类型的癫痫发作外,还可以表现为癫痫性痉挛。癫痫痉挛在无意义和移码突变中更为常见。与没有癫痫性痉挛的儿童相比,癫痫性痉挛儿童的预后较差。基因检测有助于选择减少癫痫发作的抗癫痫药物。
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引用次数: 1
Erratum: Erratum: KCNQ2 Encephalopathy and Responsiveness to Pyridoxal-5'-Phosphate. 勘误:KCNQ2脑病和对吡哆醛-5'-磷酸的反应。
IF 0.4 Pub Date : 2023-03-01 DOI: 10.1055/s-0041-1735896
Chit Kwong Chow, Ho Ming Luk, Suet Na Wong

[This corrects the article DOI: 10.1055/s-0040-1721384.].

[这更正了文章DOI: 10.1055/s-0040-1721384.]。
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引用次数: 0
Genetic Defects in Children with Cardiac Anomalies/Malformations: Noonan and CFC Syndromes. 心脏异常/畸形儿童的遗传缺陷:Noonan综合征和CFC综合征。
IF 0.4 Pub Date : 2023-03-01 DOI: 10.1055/s-0040-1721441
Divya Kumari, Deepti Chaudhary, Inusha Panigrahi, Manoj K Rohit

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.

儿童心脏缺陷表现出显著的表型和遗传异质性。有了先进的基因技术,这些疾病可以通过专门的检测及早发现。产前检查是目前可行的改进超声检查和胎儿超声心动图。在这里,我们报告两例努南综合征和心皮肤综合征的患者在三级保健中心的遗传单位看到的心脏缺陷,有或没有发育迟缓,身材矮小,畸形。在这些情况下,也有恶性肿瘤的风险增加,如少年髓细胞白血病。随着下一代测序技术的出现,这类疾病的明确诊断和咨询成为可能。
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引用次数: 1
Kindler's Syndrome with Recurrent Neutropenia: Report of Two Cases from Saudi Arabia. 金德勒综合征伴复发性中性粒细胞减少症:沙特阿拉伯2例报告。
IF 0.4 Pub Date : 2023-03-01 DOI: 10.1055/s-0040-1721077
Yousef Binamer, Muzamil A Chisti

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 FERMT1 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 FERMT1 are a common mechanism of KS and as such confirm the diagnosis of KS in our patients even though the presentation was atypical.

金德勒综合征是一种罕见的常染色体隐性遗传的光敏性疾病。它的特点是在婴儿期和儿童期肢端起泡,进行性千皮病,皮肤萎缩,异常光敏性和牙龈脆弱。除了这些主要特征外,文献中还报道了许多次要的表现。我们报告两例非典型特征的综合征和复发性中性粒细胞减少的新特征。全外显子组测序分析采用下一代测序技术,在两名患者中检测到FERMT1的纯合功能缺失(LOF)变体。根据美国医学遗传学和基因组学学院的指导方针,这种变异被归类为致病性变异。FERMT1的纯合子LOF变异是KS的常见机制,因此在我们的患者中证实了KS的诊断,尽管其表现不典型。
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引用次数: 0
Homozygous Novel Variants in the Glycine Decarboxylase Gene Associated with Nonketotic Hyperglycinemia in a Distinct Population. 不同人群中与非酮症高血糖症相关的甘氨酸脱羧酶基因的纯合新变异。
IF 0.4 Pub Date : 2023-03-01 DOI: 10.1055/s-0041-1729741
Heba Salah Abdelkhalek Elabd, Fatma Bastaki, Mohamed Khalifa

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 GLDC . 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 GLDC . 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 GLDC 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.

甘氨酸脑病(GE),也被称为非酮症型高甘氨酸血症(NKH)是一种常染色体隐性遗传病,由于甘氨酸切割酶系统的原发性缺陷。其特点是血浆和脑脊液(CSF)中甘氨酸水平升高,脑脊液与血浆甘氨酸比值升高。线粒体甘氨酸切割系统的三个基因突变已被发现引起NKH。大多数患者的GLDC都有突变。在本报告中,我们报告了5例来自中东家庭的NKH新患者。他们都是由近亲父母所生,其中两人有类似患病的兄弟姐妹的家族史。所有患者均表现为新生儿脑病伴发作。他们的诊断经临床怀疑和生化证实。对5例患者的DNA序列分析显示,GLDC中存在5种不同的致病或可能致病的变异。三个是错义变异(c.2675C > T;p.Ala892Val), (c.2512A > G;p.Asn838Asp)和(C . 2943a > C;p.Lys981Asn);一个是内含子错义变异(c.1402-2A > T)导致外显子缺失,另一个是42个氨基酸缺失(c.1927- _2052 + ?del)。所有的变异都是新颖的纯合子。这些变异的致病性是根据美国医学遗传学学院(ACMG)的变异分类和计算机分析确定的。另一个新的纯合变异(c.1384C > G;p.Leu462Val),分类为可能良性。在这些患者的GLDC中发现的新变异是NKH发病机制的基础,特别是对中东人群。这扩大了NKH的突变谱,包括一个以前没有研究过的独特的民族人群。
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引用次数: 0
期刊
Journal of pediatric genetics
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