A case of necrotizing enterocolitis associated with adenovirus infection in a term infant with 22q11 deletion syndrome

Infections with adenoviruses are a common problem in the pediatric population. Normally asymptomatic to mild, those infections tend to take a more severe course in immunocompromised patients. 22q11 deletion syndrome (22q11DS) represents a common genetic disorder causing immunodeficiency from thymic hypoplasia or aplasia, heart defects, a characteristic facial appearance, and velopharyngeal dysfunction. Necrotizing enterocolitis (NEC) is a frequent gastrointestinal emergency observed in neonatal intensive care units. The occurrence of NEC is more prevalent in preterm infants. However, there are cases in term infants, but usually, they are associated with predisposing disorders. In this case report, a child is presented with 22q11DS that postnatally developed NEC associated with an adenoviral infection. Although other viruses such as toroviruses or cytomegaloviruses have been implicated in the pathogenesis of NEC in preterm infants, we could not find any report in the recent medical literature describing an association between adenoviral infections, NEC, and 22q11DS in a term infant.     

Mapping cortical thickness in children with 22q11.2 deletions

The 22q11.2 deletion syndrome (velocardiofacial/DiGeorge syndrome, 22q11.2DS) involves cardiac and craniofacial anomalies, marked deficits in visuospatial cognition, and elevated rates of psychosis. Although the mechanism is unknown, characteristic brain alterations may predispose to development of psychosis and cognitive deficits in 22q11DS. We applied cortical pattern matching and new methods for measuring cortical thickness in millimeters to structural magnetic resonance images of 21 children with confirmed 22q11.2 deletions and 13 demographically matched healthy comparison subjects. Thickness was mapped at 65 536 homologous points, based on 3-dimensional distance from the cortical gray-white matter interface to the external gray-cerebrospinal fluid boundary. A pattern of regionally specific cortical thinning was observed in superior parietal cortices and right parietooccipital cortex, regions critical for visuospatial processing, and bilaterally in the most inferior portion of the inferior frontal gyrus (pars orbitalis), a key area for language development. Several of the 30 genes encoded in the deleted segment are highly expressed in the developing brain and known to affect early neuronal migration. These brain maps reveal how haploinsufficiency for such genes can affect cortical development and suggest a possible underlying pathophysiology of the neurobehavioral phenotype.     

Caries-related saliva properties in individuals with 22q11 deletion syndrome.

OBJECTIVES: The aims were to compare saliva secretion rate, buffer capacity, cariogenic bacteria, total protein, IgA, and electrolytes between patients with 22q11 deletion syndrome (22q11DS) and control subjects and to study correlations between saliva and serum levels of IgA and electrolytes in 22q11DS patients. STUDY DESIGN: Twenty-nine consecutive 22q11DS patients (mean age 12.6 years) and matched healthy control subjects were clinically examined, and stimulated saliva samples were collected. RESULTS: Patients with 22q11DS had impaired salivary secretion rate (P < .01) and buffer capacity (P < .05), higher numbers of cariogenic bacteria (P < .01), increased saliva protein concentrations (P < .001), and reduced output of electrolytes (P < .001-.05) compared with control subjects. A correlation between concentration in serum and saliva was found only for IgA (r = .622; P < .01). CONCLUSIONS: Different salivary components were affected in patients with 22q11DS, which may explain the increased caries risk seen in these patients.     

Phenotypic expansion of the supernumerary derivative (22) chromosome syndrome: VACTERL and Hirschsprung's disease

Phenotypically healthy carriers of the balanced 11;22 translocation, the most frequent non-Robertsonian constitutional translocation known in human beings, are at risk of having a progeny with supernumerary derivative (22)t(11;22) syndrome [der(22) syndrome]. We present the cases of 2 male patients with supernumerary der(22) syndrome [47,XY,+der(22)t(11;22)(q23;q11.2)mat], yielding partial trisomy for 22pter-q11 and 11q23-qter. These cases expand the phenotype of the der(22) syndrome, with the first case highlighting the phenotypic overlap of VACTERL and the second adding Hirschsprung's disease and intestinal malrotation to the list of associated anorectal anomalies. Because der(22) syndrome and cat eye syndrome (partial tetrasomy of 22q11) share a similar region of extra dosage on 22q11 and both typically manifest an anorectal phenotype, a dosage-sensitive gene for anorectal anomalies may be present in this locus.     

Hypogonadotropic hypogonadism associated with another small supernumerary marker chromosome (sSMC) derived from chromosome 22, a case report

The idiopathic hypogonadotropic hypogonadism (IHH) is portrayed as missing or fragmented pubescence, cryptorchidism, small penis, and infertility. Clinically it is characterized by the low level of sex steroids and gonadotropins, normal radiographic findings of the hypothalamic-pituitary areas, and normal baseline and reserve testing of the rest of the hypothalamic-pituitary axes. Delay puberty and infertility result from an abnormal pattern of episodic GnRH secretion. Mutation in a wide range of genes can clarify ~40% of the reasons for IHH, with the majority remaining hereditarily uncharacterized. New and innovative molecular tools enhance our understanding of the molecular controls underlying pubertal development. In this report, we aim to present a 26-year-old male of IHH associated with a small supernumerary marker chromosome (sSMC) that originated from chromosome 22. The G-banding analysis revealed a karyotype of 47,XY,+mar. High-throughput DNA sequencing identified an 8.54 Mb duplication of 22q11.1-q11.23 encompassing all the region of 22q11 duplication syndrome. Pedigree analysis showed that his mother has carried a balanced reciprocal translocation between Chromosomes 22 and X[t(X;22)]. To the best of our knowledge, this is the second confirmed case of IHH with an sSMC deriving from chromosome 22. Based on our study, the duplicated chromosome fragment 22q11.1-q11.23 might be the reason for the phenotype of our case. Meanwhile, High-throughput DNA sequencing combined with cytogenetic analysis can provide a more accurate clinical diagnosis for patients carrying sSMCs.     

The role of 22q11.2 deletion syndrome in the relationship between congenital heart disease and scoliosis

BACKGROUND CONTEXTFor over four decades, clinicians and researchers have suggested a relationship between congenital heart disease (CHD) and scoliosis, attributed to either the disease itself or to the long-term effects of cardiac surgery on the immature thoracic cage. However, no study has yet accounted for 22q11.2 deletion syndrome (22q11.2DS), the second most common cause of CHD after Down syndrome. 22q11.2DS has a scoliosis risk of 50%, but within 22q11.2DS a previous report found no significant association between scoliosis and CHD. We, therefore, hypothesized that scoliosis within a CHD cohort would be related to an underlying 22q11.2 deletion.PURPOSETo determine the prevalence of scoliosis in CHD patients with and without 22q11.2DS.STUDY DESIGN/SETTINGCross-sectional.PATIENT SAMPLEA well-characterized existing database of 315 adults with CHD (primarily tetralogy of Fallot), with (n=86) and without (n=229) 22q11.2DS, matched by sex and CHD severity, and excluding other known syndromic diagnoses. We compared the scoliosis prevalence of patients with 22q11.2DS and CHD patients to the prevalence of scoliosis in a cohort of adults with 22q11.2DS without CHD based on medical records.OUTCOME MEASURESPresence of scoliosis (Cobb angle ≥10°).METHODSWe systematically determined the presence of scoliosis in all included patients using chest radiographs, blind to genetic diagnosis. Besides 22q11.2DS, we analyzed other suspected risk factors for scoliosis using a regression model: thoracotomy before the age of 12 years, severe CHD type and sex.RESULTSThe prevalence of scoliosis in adults with CHD and 22q11.2DS (n=46, 53.5%) was significantly greater than in those without 22q11.2DS (n=18, 7.9%, p<.0001). The presence of a 22q11.2 deletion (odds ratio [OR] 25.4, 95% confidence interval [95% CI] 11.2–57.4, p<.0001), a history of thoracotomy before the age of 12 years (OR 3.5, 95% CI 1.6–8.1, p=.0027) and most complex CHD class (OR 2.3, 95% CI 1.1–4.7, p=.0196), but not sex, were significant independent predictors of scoliosis. In the 22q11.2DS group, a right-sided aortic arch was associated with a left thoracic scoliotic curve (p=.036).CONCLUSIONSThe prevalence of scoliosis in those with CHD but without a 22q11.2 deletion approximates that of the general population. However, in the CHD population with a 22q11.2 deletion, the prevalence of scoliosis approximates that of others with 22q11.2DS. The pediatric surgical approach and severity of CHD were weaker independent contributors as compared to the 22q11.2 deletion. The results support the importance of a genetic diagnosis of 22q11.2DS to the risk of developing scoliosis in individuals with CHD. The 22q11.2 deletion may represent a common etiopathogenetic pathway for both CHD and scoliosis, possibly involving early laterality mechanisms.     

Self-reported functional health status following interrupted aortic arch repair: A Congenital Heart Surgeons' Society Study

Objectives

Improved survival after congenital heart surgery has led to interest in functional health status. We sought to identify factors associated with self-reported functional health status in adolescents and young adults with repaired interrupted aortic arch.

1例环状22号染色体综合征致无精子症并文献复习

目的:探讨1例患有环状22号染色体综合征的无精子症患者的临床表型和遗传学特征。方法:收集1例环状22号染色体综合征患者的临床信息,结合文献加以分析。结果:患者身材矮小,体检双侧睾丸小,质地软,精液检查示无精子症。染色体核型为46,XY,r(22)(p11,q25),性激素示睾酮低下,睾丸大体病理示组织脆、易拉断,病理镜检示生精小管内支持细胞及生殖细胞数量均减少,细胞层次变薄,生殖细胞均为精原细胞,未见精母细胞和精子细胞,完全无精子发生。部分生精小管的管壁可见间质轻度纤维化。结论:环状22号染色体综合征的临床表型基本正常,但这种遗传异常使患者的睾丸组织严重受损,生精过程被阻滞而导致了无精子症。     

Advanced imaging of the cervical spine and spinal cord in 22q11.2 deletion syndrome: age-matched, double-cohort, controlled study

Purpose  The 22q11.2 deletion syndrome is a common genetic syndrome with a wide spectrum of abnormalities. We have previously described multiple anomalies of the upper cervical spine in this disorder. The objective of this study was to use advanced imaging to further define the morphology of the cervical spine and spinal cord in the 22q11.2 deletion syndrome, with a comparison to age-matched controls. Methods  A total of 32 patients with a 22q11.2 deletion underwent advanced imaging (computed tomography/magnetic resonance imaging; CT/MRI) of the cervical spine. In 27 patients, space available for the cord (SAC); the sagittal diameter of the vertebral body, spinal canal, cerebrospinal fluid (CSF), and spinal cord; and the cross sectional area of the spinal canal, CSF, and spinal cord were measured at each cervical level and compared to 29 age-matched controls. Statistical analysis was performed and potential implications were hypothesized. Results  In 22q11.2 patients, advanced imaging identified 40 pathologies not evident on plain radiographs with potential mechanical and/or neurological implications. These patients also had significantly smaller values (P ≤ 0.05) of the following parameters at one or more cervical levels, relative to age-matched controls: width of the vertebral body, spinal canal, CSF, and spinal cord; area of the spinal canal, CSF, and spinal cord. Neurologic symptoms were observed in 4/32 patients, with one patient requiring surgical intervention. Conclusions  Advanced imaging of the cervical spine can detect findings not evident on plain radiographs in the 22q11.2 deletion syndrome. CT and/or MRI may be indicated when there is a high index of suspicion for clinical instability or neurologic compromise in order to rule out dynamic encroachment or impending neurologic sequelae. Spinal canal and spinal cord dimensions are reduced in these patients relative to controls with currently unknown clinical significance.     

Failure of neuraxial anaesthesia in a patient with Velocardiofacial syndrome

Velocardiofacial or 22q11 deletion syndrome is a genetic condition caused by deletion 22q11, the deletion of a small segment of the long arm of chromosome 22. To our knowledge this is the first case report of a woman with Velocardiofacial syndrome presenting in late pregnancy for caesarean delivery. She had undergone a Tetralogy of Fallot repair as an infant and had residual pulmonary regurgitation. In addition examination revealed micrognathia and scoliosis. Neuraxial anaesthesia was unsuccessful and subsequent conversion to general anaesthesia was necessary despite concerns regarding her facial abnormalities, pulmonary regurgitation and mild intellectual impairment.     

Anesthesia in a patient with chromosome 11;22 translocation: a case report and literature review

Chromosome 11;22 translocation is a rare genetic condition, which results in characteristic features some of which may present problems when these children require surgery and anesthesia. We describe a child with this chromosomal variant who presented for surgery and anesthesia. The case report and review of the literature is presented here.     

22q11 Deletion in children with cleft lip and palate--is routine screening justified?

OBJECTIVE: To ascertain the prevalence of 22q11 deletion in children with a diagnosis of cleft lip and/or palate that had been referred to the Cleft Lip & Palate Service, Newcastle-upon-Tyne. DESIGN: Retrospective analysis of results of 22q11 FISH testing performed in all such referrals. PARTICIPANTS: 191 children, of whom 13 had a bilateral cleft lip and palate, two had a median cleft, 77 had a cleft palate only, 44 had a unilateral cleft lip, 47 had a unilateral cleft lip and palate and eight had a submucous cleft palate. RESULTS: nine patients had a positive 22q11 FISH test. CONCLUSION: This represents a higher percentage than has been previously reported. All children with cleft lip and/or palate should routinely have a 22q11 FISH test in view of the implications of a diagnosis of velocardiofacial syndrome.     

Congenital bile duct anomalies (biliary atresia) and chromosome 22 aneuploidy

Biliary atresia is a disease of unknown etiology but not usually thought to have a significant genetic predisposition. We report 5 infants with various forms of chromosome 22 aneuploidy as follows: 2 infants who have classical cat-eye syndrome, 2 who have partial duplication of chromosome 22 (supernumerary der(22) syndrome), and 1 who is mosaic for trisomy 22. All of these infants had significant congenital bile duct anomalies (specifically biliary atresia, n = 4)—that was the most important component of their clinical presentation. We consider whether this has possible implications about the genetic contribution to the etiology of biliary atresia.     

正常生育男性及少精子症患者精子中由回文序列介导的染色体突变

目的:探讨人类精子中由回文序列介导的一类新型染色体突变的发生规律。方法:对28例少精子症以及32例正常生育男性的精液样本,采用巢式及多重巢式PCR检测其中特定的易位DNA序列,并对结果进行统计学分析。结果:49例存在t(11;22)易位突变,其中少精子症组22例,正常生育组27例,两组之间差异无显著性(χ2=0.336,P>0.05)。此外,至少4例亦存在t(1;22)(p21.2;q11.2)、t(17;22)(q11;q11)或t(X;22)(q27;q11)易位突变。易位的发生与精子密度(r=-0.389,P<0.05)、活动率(r=-0.397,P<0.05)呈负相关,而与精液量或供精者年龄无显著相关;未发现易位突变率与回文序列的相似度之间存在关联。结论:由回文序列介导的染色体突变在人类精子中普遍存在,且与精子密度、活动率相关。对这类突变进行动态量化检测可望提供一种从分子水平评估精子质量的手段。     

A novel reciprocal chromosome translocation t(11;22)(p13;q12) in an intraabdominal desmoplastic small round-cell tumor.

We report an intraabdominal desmoplastic small round-cell tumor that contains a novel reciprocal chromosome translocation t(11;22)(p13;q12). The tumor showed a reciprocal chromosome translocation which is different from the (11;22)(q24;q12) translocations seen in Ewing's and other small-cell tumors but affects the same break-point on chromosome 22(q12). This reciprocal chromosome translocation may prove to be a marker for intraabdominal desmoplastic small round-cell tumors.     

Down's syndrome as a factor in the diagnosis, management, and outcome in patients of Morgagni hernia

Purpose

The purpose was to study the impact of Down's syndrome (DS) in the diagnosis, management, and outcomes of patients with Morgagni hernia (MH).

Methods

Twenty-two (22) patients with MH treated at a tertiary center were retrospectively studied for history, findings, associated anomalies, referral diagnoses, hospital admissions, radiological procedures for diagnosis, age at which operated on, operative procedure, complications, and recurrences. Eleven did not have DS (group 1); 11 others had associated DS (group 2). The ages at operation were compared in the 2 groups using the Mann-Whitney test. More than 3 hospital admissions for symptoms and signs relevant to MH before a diagnosis of MH were considered a “delayed diagnosis.”

Results

Twenty-two patients (7 females, 15 males) aged 3 months to 10 years were seen. They presented with respiratory distress (n = 16), with vomiting (n = 5), with intestinal obstruction (n = 1), by serendipity (n = 2), and with recurrence from another hospital (n = 1). The mean age of group 1 was 14.5 months, and that of group 2 was 29.18 months; the difference was not significant (P = .621). Nine patients of group 2 were “delayed diagnosis” compared with 2 in group 1. Both delays from group 1 had severe associated anomalies. All patients underwent operative correction (17 open and 5 laparoscopic repairs). Two had recurrences, one operated on by the open method by us and another laparoscopically by the Lima technique at another center. Both had DS. Both were reoperated on by the open method.

Conclusions

The diagnosis of MH may be strikingly delayed when associated with DS or other severe congenital anomalies. Morgagni hernia should be strongly considered in patients with DS admitted repeatedly for chest infections. Chest x-rays in 2 planes may avoid misdiagnosis of MH. Both open and laparoscopic methods have proven satisfactory as operative treatment of MH. Recurrences were seen in patients with DS, which may be corrected by laparotomy or laparoscopically. We feel that resecting the sac and approximating the posterior lip of the defect to the anterior abdominal wall, whether in open or laparoscopic methods, may give stronger repairs, which may avoid recurrence.     

Dumping Syndrome and Postbariatric Hypoglycemia: Supporting Evidence for a Common Etiology

BackgroundDumping syndrome (DS) and postbariatric hypoglycemia (PBH) are frequent complications of bariatric surgery. Previously known as “early and late dumping,” these complications have been separated due to differences in their onset and behaviors.ObjectivesTo investigate a potentially common etiology of DS and PBH using an analysis of a mixed meal test (MMT) study.SettingA large teaching hospital in the Netherlands.MethodsFrom all patients who underwent bariatric surgery in 2008–2011, a random selection completed an MMT (n = 47). Patients scored complaints related to DS and PBH with a standardized questionnaire at several time intervals. The groups were divided into patients with (DS+; n = 22) and without (DS-; n = 25) an increase in DS symptoms after the start of the MMT. Glucose and gut hormone levels were compared. Hypoglycemia was defined as a blood glucose level below 3.3 mmol/L.ResultsThe DS+ group had lower blood glucose values compared to the DS- group, which reached significance at 90 and 120 minutes (P < .05). For the DS+ group, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and satiety were higher at various time intervals (P < .05) compared to the DS- group. No differences were found for insulin and hunger score. GLP-1 and PYY were correlated with symptoms of DS.ConclusionPatients with DS complaints had lower postprandial glucose values. GLP-1 and PYY values were elevated in the DS+ group early and late during the test. These hormones also correlated with DS. These findings support the hypothesis of a common etiology of DS and PBH and a role of GLP-1 and PYY in both complications.     

Microsatellite analysis in multiple chromosomal regions as a prognostic indicator of primary bladder cancer

This study investigated gene abnormalities in bladder cancer patients and the relationship between chromosomal alteration and the clinical outcome using microsatellite analysis. A total of 45 human bladder tumor patients were analyzed. The microsatellite markers for 18q21.1 (D18S46, D18S363, and D18S474), 9p21–22 (D9S171, D9S747, D9S1747, and IFNA), and 17p13.1 (TP53) were used for the loss of heterozygosity (LOH) detection. The clinical outcomes were estimated with univariate and multivariate analyses. The results show that patients with LOHs in 18q21.1 and 9p21–22 exhibited a significantly poor prognosis. LOHs of these chromosomal regions had the most predictable potential compared with the other known prognostic factors, such as tumor grade, TNM stage, and age. It is concluded that microsatellite analysis for 18q21.1 and 9p21–22 is capable of predicting the clinical outcome of bladder cancer patients. Received: 24 April 1999 / Accepted: 28 July 2000     

Bone mineral mass in males and females with and without Down syndrome

Previous bone comparison studies between subjects with and without Down syndrome (DS) were performed using bone mineral density (BMD) as the dependent variable, and mainly focused on lumbar spine region. The purpose of this study was to compare bone mineral mass adjusted for bone and body size, in limbs, lumbar spine, and femoral neck between males and females with and without DS. Subjects were 66 females (33 with DS) and 68 males (34 with DS) aged 14–40 years. Analysis of covariance (ANCOVA) was used to analyze the main and interaction effects of gender and condition on bone mineral mass. For this purpose, adjusted bone mineral content (BMC) (for bone area, height, and age), volumetric bone mineral density (vBMD) (for age), and composite indices of femoral neck strength (for age), were used as the dependent variables, corrected additionally for body composition variables selected by regression analysis. ANCOVA revealed lower lumbar spine vBMD in DS than in control subjects with (–5%, P=0.013), or without body weight adjustments (–6%, P=0.003). In femoral neck, the mean of each strength measure was also lower in DS than in control subjects. Mean differences between groups were, with and without additional adjustments for fat mass, respectively, –8% (P=0.009), and –13% (P<0.001) for compressive strength, –11% (P=0.036), and –16% (P=0.004) for bending strength, and –7% (P=0.031), and –11% (P=0.002) for impact strength. These lumbar spine and femoral neck differences between groups were highest in young adults (>20 years) and not significant in adolescents. No interaction effect was observed between gender and condition. In conclusion, DS was shown to be a risk factor for low vBMD in lumbar spine, and for diminished bone strength relative to the loads that the femoral neck must bear. Body composition did not reach statistical significance as predictor of bone differences in these sites between subjects with and without DS, suggesting that other factors may be involved in this detrimental bone status, particularly in young adults compared with adolescents.     

染色体平衡易位患者精子染色体荧光原位杂交分析

目的:探讨外周血染色体平衡易位患者在精子发生过程中染色体分离模式,了解各分离模式产生精子所占比例,预测染色体平衡易位携带者在胚胎移植前遗传学诊断(PGD)中得到正常表型胚胎的概率,评估其进行PGD的风险。方法:应用三色荧光原位杂交(FISH)对4例染色体平衡易位患者46,XY,t(9;11)(q22;q21)、46,XY,t(11;22)(q23;q11)、45,XY,t(13q;15q)、45,XY,t(13q;14q)进行精子相关染色体分析,计算出各染色体分离模式产生精子所占比例,同时以染色体正常男性的正常精液作为对照。结果:上述4例异常精子所占比例分别为50.86%、58.33%、13.00%和22.82%,均明显高于对照组(0.85%、1.63%、1.60%和1.37%)。结论:通过FISH检测染色体平衡易位患者精子染色体,有助于预测染色体平衡易位携带者在PGD过程中的风险,从而选择应用PGD。