Severe feeding problems and congenital laryngostenosis in a patient with 3q23 deletion

Common clinical features of patients with 3q23 deletion include the phenotype of BPES (blepharophimosis, ptosis, epicanthus inversus and telecanthus syndrome), growth and mental retardation, microcephaly, ear and nose dysmorphism and joint and digit abnormalities. We report on a 3-year-old girl with the phenotype of BPES, mental retardation, facial dysmorphism and camptodactyly. In addition, she had a congenitally small larynx and severe, chronic feeding difficulties. Chromosome studies revealed an interstitial deletion in the long arm of chromosome 3: del(3)(q23-q25) Conclusion Congenital laryngostenosis and severe feeding problems may be part of the clinical syndrome caused by chromosome 3q23 deletion. Received: 28 January 1997 / Accepted: 25 February 1997     

“Mirror,Mirror on the Wall”… Pediatric liver transplantation in the case of situs inversus totalis with a disrupted inferior vena cava

We present the unique case of a 15‐month‐old male born with biliary atresia and situs inversus totalis and disrupted inferior vena cava who underwent a successful liver transplantation. The patient had previously undergone a failed Kasai procedure and presented with persistent hyperbilirubinemia. The patient was transplanted with a left lateral segment donor having standard arterial anatomy. Technical considerations included identifying completely replaced arterial anatomy in the recipient from the superior mesenteric artery and creating a branch patch between the gastroduodenal artery and HA, anastomosing the donor left hepatic vein to confluences of the donor left, middle, and right hepatic veins, using a “lazy‐S” configuration of portal vein anastomosis, and suspending the allograft to the abdominal wall. Post‐operatively, his liver function tests and total bilirubin normalized and he progressed to tolerating an oral diet with tube‐feed supplementation.     

Early intervention for late‐onset ornithine transcarbamylase deficiency

We report the case of a family with late‐onset ornithine transcarbamylase deficiency (OTCD). Several family members had died from OTCD, and the c.221G>A, p.Lys221Lys mutation was detected at the 3′ end of exon 6 of OTC in the X‐chromosome of some members. We provided genetic counseling on pregnancy, delivery, and neonate management to a 4th‐generation female carrier and decided on metabolic management of her child from birth. Two male patients were diagnosed with late‐onset OTCD on the basis of blood amino acid and genetic analysis, and they received arginine supplementation from the asymptomatic, early neonatal period. These children grew and developed normally, without decompensation. Patients with late‐onset OTCD can and should be diagnosed and treated in the early neonatal period, especially those from families already diagnosed with late‐onset OTCD, and family members must be provided with genetic counseling.     

A novel tissue‐based ß‐catenin gene and immunohistochemical analysis to exclude familial adenomatous polyposis among children with hepatoblastoma tumors

1 Background

The Wnt/β‐catenin pathway plays a central role in the pathogenesis of most hepatoblastomas (HBs), that is, up to 60–80% carry activating CTNNB1 mutations. HBs can however also be the first manifestation of familial adenomatous polyposis (FAP). As this is a severe disease, it is important for the patient and related family members to firmly exclude FAP at an early stage. Current diagnosis largely depends on APC germline mutation detection on genomic DNA, which is associated with 10–20% false‐negative results. Here, we establish and validate a tissue‐based β‐catenin gene and immunohistochemical analysis, which complements germline mutation screening to exclude the diagnosis of FAP among HB patients.

2 Methods

Tumor tissues of 18 HB patients, including three FAP cases were subjected to CTNNB1 exon 3 mutational analysis and immunohistochemistry comparing staining patterns for total and exon 3 specific β‐catenin antibodies.

3 Results

Our novel tissue‐based method reliably identified all three FAP patients. Their tumors were characterized by a wild‐type exon 3 sequence and a comparable nuclear staining for both antibodies. In contrast, the non‐FAP tumors carried missense CTNNB1 mutations combined with a clearly reduced staining for the exon 3 antibody, or complete loss of staining in case of lesions with exon 3 deletions.

4 Conclusion

We have successfully established and validated a novel ß‐catenin gene and immunohistochemical diagnostic method, which, when combined with routine germline DNA testing, allows the exclusion of the diagnosis of FAP among HB patients.     

Views of parents of children with sickle cell disease on pre‐implantation genetic diagnosis

Pre‐implantation genetic diagnosis (PGD) is an option for parents who have a child with sickle cell disease (SCD) to have another child without SCD. We conducted a survey of 19 parents with at least one child with SCD to investigate views on PGD. Before education, 44% of parents were aware of PGD. All parents rated PGD education as important. All parents considering another child also reported interest in using PGD if insurance covered its costs. Parents who have a child with SCD appear to be interested in PGD and educational tools informing this group about PGD should be developed.     

Kabuki综合征2例临床表型和基因变异分析

目的分析Kabuki 综合征(KS)的临床和分子遗传学特征。方法回顾分析2例以生长迟缓就诊的KS患儿的临床资料,并对患儿及其父母进行矮小相关基因组或全外显子组测序及全基因组拷贝数变异(CNV)检测。结果 2例女性患儿,均因喂养困难、生长迟缓就诊;临床表现均为特殊容貌,按年龄身长、按年龄体质量的Z评分均-2.5,发育迟缓,脊椎侧弯,头颅磁共振成像异常。例1伴右肾异位,例2伴房间隔缺损。基因检测发现,例1患儿KMT2D基因34号外显子c.10139delA(p.K3380Sfs*12)杂合变异;例2患儿KDM6A基因16号外显子c.1909-1912delTCTA(p.Ser637Thrfs*53)杂合变异,均为移码变异,新发、致病性变异。结论生长迟缓、喂养困难伴发育迟缓及特殊面容的患儿可行遗传学诊断。     

Early detection of adrenocortical carcinoma in a child with Li–Fraumeni syndrome

We report an early detection of cancer in a child with Li–Fraumeni syndrome. The proband was a 3‐year‐old male with a primitive mesenchymal tumor. Genetic analysis showed a germline TP53 mutation in codon 220 exon 6, which changed TAT → TGT and resulted in a tyrosine‐to‐cysteine amino acid substitution (Tyr220Cys). The younger sister at risk was followed, and an asymptomatic adrenal cortical carcinoma was detected 3 years later. The report highlights the importance of genetic counseling and provides an example of early detection of cancers in childhood LFS carriers. Pediatr Blood Cancer 2009;52:541–544. © 2008 Wiley‐Liss, Inc.     

Reno‐ and splenoportal anastomosis for a retransplant patient with situs inversus

PV thrombosis following pediatric LT is a serious complication that may lead to graft loss. LDLT poses limitations with regard to the availability of vein grafts for complex PV reconstructions. We herein report a unique reconstruction of the PV inflow in a one‐yr‐old boy with situs inversus undergoing re‐LDLT. The inflow was derived from the SPV and the RRV. A common channel was created utilizing a donor IMV and the recipient explant LHV as vascular conduits. With the application of innovative surgical reconstructions, pre‐existing portomesenteric thrombosis may be amenable to re‐LDLT in the pediatric population.     

Convalescent plasma for pediatric patients with SARS‐CoV‐2‐associated acute respiratory distress syndrome

There are no proven safe and effective therapies for children who develop life‐threatening complications of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Convalescent plasma (CP) has demonstrated potential benefit in adults with SARS‐CoV‐2, but has theoretical risks.We present the first report of CP in children with life‐threatening coronavirus disease 2019 (COVID‐19), providing data on four pediatric patients with acute respiratory distress syndrome. We measured donor antibody levels and recipient antibody response prior to and following CP infusion. Infusion of CP was not associated with antibody‐dependent enhancement (ADE) and did not suppress endogenous antibody response. We found CP was safe and possibly efficacious. Randomized pediatric trials are needed.     

EIF2S3基因变异致MEHMO综合征2例报告并文献复习

目的 探讨MEHMO综合征的临床特征与遗传学特点.方法 回顾分析2例确诊MEHMO综合征患儿的临床资料,并复习相关文献.结果 两例患儿均为男性.例1于2岁3个月就诊,表现为癫痫发作、智力低下、进行性痉挛性四肢瘫、小头畸形、面部畸形、身材矮小和隐睾等.例2于3月龄就诊,4个月15天龄死亡,表现为反复低血糖、小头畸形和小阴...     

Prenatal diagnosis of osteogenesis imperfecta type II by three‐dimensional computed tomography: The current state of fetal computed tomography

We report a case of osteogenesis imperfecta (OI) (OMIM166210) type II, in which a prenatal diagnosis was made by three‐dimensional computed tomography (3D‐CT). Subsequent molecular analysis revealed a recurrent, heterozygous mutation in COL1A2. Fetal CT is a powerful tool for visualizing the fetal skeleton and can provide a definitive diagnosis of fetal skeletal dysplasias; however, whether or not its employment for prenatal diagnosis is warranted in terms of fetal radiation risks remains controversial, both medically and ethically. Based on our experience, we review the current state of fetal CT for the diagnosis of skeletal dysplasias, with a discussion of the relevant literature.     

Living donor liver transplantation in situs inversus totalis with a patient‐specific three‐dimensional printed liver model

We utilized patient‐specific 3D liver models based on preoperative computed tomography images as intraoperative navigation and describe our experience. A 1‐year and 10‐month‐old girl with situs inversus totalis underwent living donor liver transplantation for biliary atresia. Information on the hepatic artery, portal vein, inferior vena cava, and liver parenchyma was extracted and segmented from computed tomography images using liver analysis software. Laser lithography produced each 3D part of the liver from these data. The 3D models of each part of the liver were molded from polyurethane resin using different colors for each part and combined together, resulting in a patient‐specific liver model. The industrial computed tomography scan of the patient‐specific 3D liver model revealed that the gaps between the liver model and the original data were <0.4 mm in the 90% area, <0.8 mm in the 98% area, and 1.53 mm at the maximum. The 3D liver model was brought into the operative field and used as intraoperative navigation for total liver resection. The procedure was finished successfully without any major intraoperative complications. In conclusion, the 3D model facilitates the identification of vessels during operations; it is possible to promptly share patients' anatomy with the operative team.     

Apert 综合征 1 例临床特征与基因类型分析

目的分析Apert综合征(AS)临床特征与基因类型。方法回顾1例AS患儿的临床资料及患儿和其父亲FGFR2基因测序结果,并复习相关文献。结果男性患儿,1岁1个月,扁头,突眼,眼距宽,耳位低,下颌小,高腭弓,无腭裂,双手五指并指并挛缩,双足五趾并趾。FGFR2基因外显子7 c.758CG,p.P253R杂合变异,父亲未检测到相关基因突变,支持Apert综合征诊断。文献检索到AS个案24例,22例明显颅面部畸形,1例轻微畸形,1例无畸形;均有手足并指/趾畸形。基因类型为S252W 13例,P253R 3例,Alu元件插入3例,基因缺失2例,杂合突变2例,序列变异1例。结论 AS患儿颅面部畸形及手足并指/趾明显,FGFR2基因以S252W、P253R突变为主。     

Aicardi-Goutières�ۺ���

??Aicardi-Goutières syndrome??AGS?? is a rare group of genetically determined disorders mainly with neurological and skin involvement. The main clinical features include multiple intracranial calcification??white matter changes??chronic lymphocytosis in cerebrospinal fluid??CSF????chilblains or other skin lesions. Seven pathogenic genes have been identified??including TREX1??RNASEH2B??RNASEH2C??RNASEH2A??SAMHD1??ADAR1 and IFIH1. This article will comprehensively discuss AGS in its pathogenesis??clinical manifestations??auxiliary examination??diagnosis and differential diagnosis??therapies and prognosis.