Growth charts for cri‐du‐chat syndrome: An international collaborative study

Low birth weight and slow growth are frequently observed in the patients with cri‐du‐chat syndrome. To provide a growth reference standard for children with cri‐du‐chat syndrome, syndrome‐specific growth charts have been developed from a combination of cross‐sectional and longitudinal measurements on 374 patients from North America, Italy, Australia, and the British Isles. The data were obtained from pediatric records, parent reporting, and personal examinations at national 5p‐ parent support group meetings in the U.S., Italy, U.K., and Australia. The growth curves include height and weight measurements for patients ages 0 to 18 years and head circumference measurements for patients ages 0 to 15 years. Birth weight was above the 5th percentile of general population in 50% of cases: mean weight 2.8 kg ± 1.85 SD for males and 2.6 kg ± 1.51 SD for females. Growth curve medians were usually at or below the 5th centile of reference populations throughout life. The median head circumference falls below the 2nd centile, and this change increases with age. The charts show that compared with the standard population, most children with cri‐du‐chat syndrome are small at birth and as they grow most, but not all, have significant microcephaly and compromised weight for age, and to a lesser extent, compromised height for age. Am. J. Med. Genet. 94:153–162, 2000. © 2000 Wiley‐Liss, Inc.     

The international standard for interleukin-6 Evaluation in an international collaborative study

Three ampouled preparations of interleukin-6 (IL-6) were evaluated by 12 laboratories in seven countries for their suitability to serve as the international standard of IL-6. The preparations were assayed using in vitro bioassays and immunoassays. On the basis of the results reported here, with the agreement of the participants in the study and with the authorization of the Expert Committee on Biological Standardization (ECBS) of the World Health Organization (WHO) one of the preparations (coded 89/548) was established as the international standard of IL-6.     

Unusual ocular findings in an infant with cri-du-chat syndrome.

A newborn male with cri-du-chat syndrome, congenital nuclear cataracts, microspherophakia, and probably ectopic lenses is reported. Microspherophakia in cri-du-chat syndrome has not been previously described. The congenital cataracts were inherited from his mother who had a balanced 5;13 translocation; the two events are considered to be coincidental and a possible 'position effect' was excluded, since the other members of her family with congenital cataracts, were chromosomally normal. This is the fourth case reported where familial cri-du-chat syndrome involves chromosomes 5p and 13q.     

Growth charts for individuals with Coffin‐Siris syndrome

Coffin‐Siris syndrome (CSS; OMIM #135900) is a rare, multisystem syndrome caused by pathogenic variants in genes encoding the BRG‐1 associated factors complex (BAF). Individuals with CSS often present with feeding difficulties and failure to thrive during infancy, in addition to a number of variable congenital anomalies. Nutritional interventions are used to support growth in this population, and growth hormone therapy has been reported in a limited number of cases. The purpose of this study was to construct CSS‐specific growth charts to better characterize the growth in this population. Anthropometric data were collected from 99 individuals enrolled in the CSS/BAF pathway international registry via a retrospective chart review. All measurements obtained after the first exposure to growth hormone therapy were excluded from this analysis. Sex‐specific centiles (5th, 50th, and 95th) were estimated for height, weight, and head circumference from birth to age 10. Cubic smoothing splines were then fit to the centile estimates and superimposed on normative male and female growth curves for comparison. The CSS patients in this cohort exhibited normal growth parameters at birth. By age 10, the weight and head circumference of the CSS cohort began to approach normal parameters. Stature, however, remained shortened at 10 years of age.     

Pierpont syndrome: a collaborative study

Pierpont syndrome is a multiple congenital anomaly syndrome with learning disability first described in 1998. There are only three patients with Pierpont syndrome who have previously been published in the literature. Details of a series of patients with features of this condition were therefore obtained retrospectively to better characterize its key features. These patients were noted to have distinctive shared facial characteristics, in addition to plantar fat pads and other limb abnormalities. Further individuals with equally striking hand and foot findings were identified whose facies were less characteristic, and hence we considered them unlikely to be affected with the same condition. Despite several patients with possible Pierpont syndrome having had high-resolution array CGH or SNP array, the etiology of this phenotype remains unknown. Whilst it is as yet unclear whether it is a single entity, there appears to be a group of patients in whom Pierpont syndrome may be a recognizable condition, with typical facies, particularly when smiling, and characteristic hand and foot findings.     

The international standard for human interleukin-2. Calibration by international collaborative study

Three lyophilized preparations of interleukin-2 coded 86/500, 86/564 and 86/504 have been evaluated in an international collaborative study for their suitability as an international standard. All of the preparations performed well in the different bioassay systems included in the study, and showed excellent stability on accelerated temperature degradation. Material similar to that in preparation 86/504 has served well as an interim reference reagent for interleukin-2 for 3 years. Therefore with the agreement of the study participants and the authorization of the Expert Committee on Biological Standardization of the World Health Organization, the preparation coded 86/504 was established in 1987 as the 1st international standard for interleukin-2, with a defined potency of 100 IU/ampoule.     

Comparative evaluation of measles virus-specific RT-PCR methods through an international collaborative study

Comparison of RT-PCR assays established in house at various places revealed that laboratories could differ in sensitivity by as much as 1,000-fold in terms of the ability to detect measles virus sequences in clinical samples. The study indicates that PCR findings, positive or negative, are questionable if they are not supported by the associated data demonstrating the overall sensitivity of the assay applied. Measles virus-specific RT-PCR-based assays need to be validated using standard virus preparation or nucleic acid-based target templates. A correlation between real-time quantitative PCR and the conventional PCR for measles virus is highly desirable.     

DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study

PurposeTo determine whether maternal plasma cell–free DNA sequencing can effectively identify trisomy 18 and 13.MethodsSixty-two pregnancies with trisomy 18 and 12 with trisomy 13 were selected from a cohort of 4,664 pregnancies along with matched euploid controls (including 212 additional Down syndrome and matched controls already reported), and their samples tested using a laboratory-developed, next-generation sequencing test. Interpretation of the results for chromosome 18 and 13 included adjustment for CG content bias.ResultsAmong the 99.1% of samples interpreted (1,971/1,988), observed trisomy 18 and 13 detection rates were 100% (59/59) and 91.7% (11/12) at false-positive rates of 0.28% and 0.97%, respectively. Among the 17 samples without an interpretation, three were trisomy 18. If z-score cutoffs for trisomy 18 and 13 were raised slightly, the overall false-positive rates for the three aneuploidies could be as low as 0.1% (2/1,688) at an overall detection rate of 98.9% (280/283) for common aneuploidies. An independent academic laboratory confirmed performance in a subset.ConclusionAmong high-risk pregnancies, sequencing circulating cell–free DNA detects nearly all cases of Down syndrome, trisomy 18, and trisomy 13, at a low false-positive rate. This can potentially reduce invasive diagnostic procedures and related fetal losses by 95%. Evidence supports clinical testing for these aneuploidies.Genet Med 2012:14(3):296–305     

Growth charts of Down syndrome in Egypt: a study of 434 children 0-36 months of age

The aim of the study was to construct new reference growth charts for weight, length and head circumference of Egyptian children with Down syndrome (DS) from birth to 36 months of age. These specific charts may be used by health professionals involved in medical, physical and developmental care of Egyptian children with Down syndrome. The study included 434 children with non-disjunction trisomy 21, 0-36 months of age. They were 54.4% males and 45.6% females and had no concomitant chronic disease (congenital heart disease, gastrointestinal malformations, hypothyroidism, and blood disorders). Overall, 1,955 observations were performed of weight, length and head circumference. The data for each sex were divided into 37 different age groups with 1-month intervals. All measurements were taken using standardized equipments and following the international recommendations. Values were statistically analyzed and growth curves were plotted as means and standard deviations (SD). Growth measurements evaluated in all age groups of both sexes were significantly lower than those of the controls. There was a gender difference in weight, length and head circumference, males with Down syndrome had higher values. In conclusion, we suggest that these new growth charts specific for Down syndrome children may be used in optimizing direct Egyptian DS children care and in providing anticipatory guidance in term of optimal physical growth and early detection of hidden factors affecting growth.     

Biotyping of Candida albicans: results of an international collaborative survey.

An agar plate system for biotyping isolates of Candida albicans was evaluated in four laboratories for 18 coded yeast isolates, each tested in triplicate on duplicate series of agar plates. The results showed that the biotyping system gave excellent intralaboratory reproducibility. However, because the concordance of data among laboratories was poor, the method must be regarded as suitable only for research applications and not for routine use.     

Maternal phenylketonuria: an international study

Maternal phenylketonuria (PKU) syndrome results in multiple congenital anomalies in the offspring, usually consisting of microcephaly, intrauterine growth retardation, dysmorphology, and congenital heart disease. Pregnancies treated preconceptionally with a phenylalanine-restricted diet and control of maternal blood phenylalanine levels within the recommended range result in normal offspring. However, in this 15-year study, several significant factors resulted in microcephaly in 27% of the offspring, and 7% exhibited serious congenital heart disease. These results occurred chiefly in women with mean IQ scores of 83 associated with low socioeconomic status and decreased educational achievement. Another important factor associated with suboptimal control of blood phenylalanine levels during pregnancy was the fact that most pregnancies were not carefully planned and occurred in women off dietary treatment with phenylalanine-restricted products. These results indicate that greater effort must be developed to assist women with PKU in remaining on diet during their reproductive years. It appears that continued adherence to the diet, resulting in normal maternal intelligence, is an important contribution to improved fetal development.     

Reliability of nucleic acid amplification for detection of Mycobacterium tuberculosis: an international collaborative quality control study among 30 laboratories.

Nucleic acid amplification to detect Mycobacterium tuberculosis in clinical specimens is increasingly used as a laboratory tool for the diagnosis of tuberculosis. However, the specificity and sensitivity of these tests may be questioned, and no standardized reagents for quality control assessment are available. To estimate the performance of amplification tests for routine diagnosis, we initiated an interlaboratory study involving 30 laboratories in 18 countries. We prepared blinded panels of 20 sputum samples containing no, 100, or 1,000 mycobacterial cells. Each laboratory was asked to detect M. tuberculosis by their routine method of nucleic acid amplification. Only five laboratories correctly identified the presence or absence of mycobacterial DNA in all 20 samples. Seven laboratories detected mycobacterial DNA in all positive samples, and 13 laboratories correctly reported the absence of DNA in the negative samples. Lack of specificity was more of a problem than lack of sensitivity. Reliability was not found to be associated with the use of any particular method. Reliable detection of M. tuberculosis in clinical samples by nucleic acid amplification techniques is possible, but many laboratories do not use adequate quality controls. This study underlines the need for good laboratory practice and reference reagents to monitor the performance of the whole assay, including pretreatment of clinical samples.     

Evaluation and validation of a PulseNet standardized pulsed-field gel electrophoresis protocol for subtyping Vibrio parahaemolyticus: an international multicenter collaborative study

The pandemic spread of Vibrio parahaemolyticus is an international public health issue. Because of the outbreak potential of the organism, it is critical to establish an internationally recognized molecular subtyping protocol for V. parahaemolyticus that is both rapid and robust as a means to monitor its further spread and to guide control measures in combination with epidemiologic data. Here we describe the results of a multicenter, multicountry validation of a new PulseNet International standardized V. parahaemolyticus pulsed-field gel electrophoresis (PFGE) protocol. The results are from a composite analysis of 36 well-characterized V. parahaemolyticus isolates from six participating laboratories, and the isolates represent predominant serotypes and various genotypes isolated from different geographic regions and time periods. The discriminatory power is very high, as 34 out of 36 sporadic V. parahaemolyticus strains tested fell into 34 distinguishable PFGE groups when the data obtained with two restriction enzymes (SfiI and NotI) were combined. PFGE was further able to cluster members of known pandemic serogroups. The study also identified quality measures which may affect the performance of the protocol. Nonadherence to the recommended procedure may lead to high background in the PFGE gel patterns, partial digestion, and poor fragment resolution. When these quality measures were implemented, the PulseNet V. parahaemolyticus protocol was found to be both robust and reproducible among the collaborating laboratories.     

Auditory pathology in cri-du-chat (5p-) syndrome: phenotypic evidence for auditory neuropathy

5p-(cri-du-chat syndrome) is a well-defined clinical entity presenting with phenotypic and cytogenetic variability. Despite recognition that abnormalities in audition are common, limited reports on auditory functioning in affected individuals are available. The current study presents a case illustrating the auditory functioning in a 22-month-old patient diagnosed with 5p- syndrome, karyotype 46,XX,del(5)(p13). Auditory neuropathy was diagnosed based on abnormal auditory evoked potentials with neural components suggesting severe to profound hearing loss in the presence of cochlear microphonic responses and behavioral reactions to sound at mild to moderate hearing levels. The current case and a review of available reports indicate that auditory neuropathy or neural dys-synchrony may be another phenotype of the condition possibly related to abnormal expression of the protein beta-catenin mapped to 5p. Implications are for routine and diagnostic specific assessments of auditory functioning and for employment of non-verbal communication methods in early intervention.     

High incidences of DNA ploidy abnormalities in tongue squamous cell carcinoma of young patients: an international collaborative study

Santos‐Silva A R, Ribeiro A C P, Soubhia A M P, Miyahara G I, Carlos R, Speight P M, Hunter K D, Torres‐Rendon A, Vargas P A & Lopes M A (2011) Histopathology  58 , 1127–1135
High incidences of DNA ploidy abnormalities in tongue squamous cell carcinoma of young patients: an international collaborative study Aims: This multi‐centre analysis assessed the DNA content of TSCC in 37 young patients (<40 years) and 28 old patients (>50 years) and determined the correlation of DNA ploidy findings with clinicopathological data. Methods and results: Image cytometry was carried out using an automated cellular imaging system on Feulgen‐stained histological sections to obtain high‐fidelity DNA histograms. Among young patients, 37.8% were females compared to 18.7% in the older group (P = 0.002). In total, 48.6% patients were non‐smokers and 40.5% were non‐drinkers compared to 10.7% non‐smokers and non‐drinkers in the older group (P < 0.0001). TNM, clinical stage of disease and histological grade of differentiation did not differ between groups. Tumour aneuploidy was detected in 86.5% and tetraploidy in 24.3% young patients; this was significantly greater than in the older group where 64.3% were aneuploid (P < 0.0001) and 7.2% tetraploid (P < 0.0001). The mean values of DNA index (DI) and DNA heterogeneity index as well as the percentage of cells with DI exceeding 5N were higher in young patients (P < 0.0001). Conclusions: Young patients with TSCC represent a distinct clinical entity. The high incidence of DNA ploidy abnormalities suggest that they may have increased genomic instability and indicates underlying genetic differences between TSCC in young and older patients.